Henoch-Schönlein purpura (HSP) during treatment with anastrozole.
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Aged↗
Biomedical subjects
G Ballerini
Publications and source records attributed to G Ballerini.
Gonadotropins and inhibins along the development of a luteinized rat ovarian tumor.
Luteinized intrasplenic ovarian tumors develop in response to high circulating gonadotropins. The relationship between tumor development, gonadotropins and inhibins was studied. Tumor-bearing animals were sacrificed weekly along the first 6 weeks of development. Inhibins were measured by enzyme-linked immunosorbent assay (ELISA), serum gonadotropins, GH and IGF-1 by RIA. Inhibin subunit mRNAs were determined by Northern blot. Tumor histology was examined. Ovarian grafts grew significantly along development. LH increased ten-fold on week 1; a further significant increment was observed on week 3. FSH peaked on weeks 1 and 2 and fell significantly thereafter. Serum inhibins markedly increased on weeks 3-5. Tumor inhibin A content and mRNA levels for alpha and beta A subunits also increased on week 3. Inverse correlations between inhibins and FSH and direct correlations between inhibins and LH were observed. Tumor inhibin A and IGF-1 contents correlated significantly. Increasing levels of luteinization were observed along tumor development. These luteinized tumors develop mainly in response to LH, since growth continues under FSH inhibition. The active inhibin secretion and the positive correlation between inhibins and LH suggests that LH may be the main driving force behind this production, while growth factors produced by the gonads may also participate in their regulation.
Animals↗
Fluid-structure interaction within realistic three-dimensional models of the aneurysmatic aorta as a guidance to assess the risk of rupture of the aneurysm.
Abdominal aortic aneurysm (AAA) disease is a degenerating process whose ultimate event is the rupture of the vessel wall. Rupture occurs when the stresses acting on the wall rise above the strength of the AAA wall tissue. The complex mechanical interaction between blood flow and wall dynamics in a three dimensional custom model of a patient AAA was studied by means of computational coupled fluid-structure interaction analysis. Real 3D AAA geometry is obtained from CT scans image processing. The results provide a quantitative local evaluation of the stresses due to local structural and fluid dynamic conditions. The method accounts for the complex geometry of the aneurysm, the presence of a thrombus and the interaction between solid and fluid. A proven clinical efficacy may promote the method as a tool to determine factual aneurysm risk of rupture and aid the surgeon to refer elective surgery patients.
Aorta, Abdominal↗
Giant anastomotic pseudoaneurysm after Bentall operation causing late postoperative cardiogenic shock.
Pseudoaneurysm of the ascending aorta is a rare but severe complication occurring after composite graft surgery for combined aortic valve and ascending aorta disease. The diagnosis of this condition can be difficult because anastomotic pseudoaneurysms show highly variable clinical features depending on the site of the aortic dehiscence and on the involvement of the surrounding structures. We report an unusual case of a late postoperative aortic graft dehiscence, causing acute right heart failure.
Adult↗
Thrombosis of mechanical heart valve prostheses: revisiting the role of fluoroscopy.
Prosthetic valve thrombosis is a rare but potentially fatal complication of heart valve replacement. Symptoms may be misleading, yet the condition may rapidly lead to death. A prompt diagnosis is therefore crucial. Ultrasound is the most often used technique for evaluating prosthesis dysfunction. We describe two cases of prosthesis thrombosis with negative Doppler results but with distinctly abnormal leaflet motion at fluoroscopy. A correct diagnosis would have been missed if the Doppler evaluation alone was relied on. Fluoroscopy should always form part of the diagnostic work-up in patients with artificial heart valves.
Coronary Thrombosis↗
Low folate levels and thermolabile methylenetetrahydrofolate reductase as primary determinant of mild hyperhomocystinemia in normal and thromboembolic subjects.
Several studies have indicated that mild to moderate hyperhomocystinemia is a common cause of arterial occlusive disease. Whether hyperhomocystinemia per se is an independent risk factor for vein thromboembolism (VTE) is still somewhat controversial. Both genetic and nutritional factors influence plasma homocysteine levels. Therefore, we evaluated plasma total homocysteine (tHcy), folate, and vitamin B12 levels and established, by polymerase chain reaction, the presence of the C677T mutation (A223V) in the methylenetetrahydrofolate reductase (MTHFR) gene in 220 cases with VTE without well-established prothrombotic defects. As a control group, 220 healthy subjects from the same geographic area as the cases were investigated. Hyperhomocystinemia was defined as a plasma tHcy level above the 95th percentile in the controls (18.05 micromol/L). Hyperhomocystinemia was found in 16% of cases (odds ratio=3.59; P<0.001); deficiencies of folate (<2.47 ng/mL) or vitamin B12 (<165 pg/mL), defined as values below the 5th percentile in controls, were found in 17.7% (P<0.001) and 12.3% (P=0.015) of cases, respectively. The homozygous condition for the MTHFR mutation (VV) was present in 28.2% of cases and 17.7% of controls (odds ratio=1.82; P=0.013). Comparing only the idiopathic forms of VTE (n=80/220; 36.3%) with normal controls, individuals with hyperhomocystinemia, or individuals homozygous for MTHFR mutation increased the odds ratios to 4.03 (P=0.005) and 2.11 (P=0.018), respectively. No statistically significant difference was observed in the MTHFR genotype distribution of cases and controls with hyperhomocystinemia (P=0.386); however, the normal MTHFR genotype (AA) appeared in control subjects only when tHcy levels were below the 80th percentile (10.57 micromol/L) of the distribution, whereas in case patients, it was present at the highest tHcy levels. A strong association between mutated homozygosity (VV), low folate levels, and hyperhomocystinemia was found in both groups. We conclude that in patients with VTE who do not have coexisting prothrombotic defects, hyperhomocystinemia increases the risk of developing idiopathic and venous thrombosis; the homozygous condition for the MTHFR mutation confers a moderate risk but, together with low folate levels, it is the main determinant of mild hyperhomocystinemia in normal and thromboembolic populations.
Adult↗
Coexistence of antithrombin deficiency, factor V Leiden and hyperhomocysteinemia in a thrombotic family.
We report a thrombotic family with combined type I antithrombin deficiency and factor V Leiden (factor V-R506Q) in which the proposita, affected by recurrent venous and arterial thrombosis, was also characterized by mild hyperhomocysteinemia (28 micromol/l; normal <18.5 micromol/l). Her two thrombotic sisters, with normal antithrombin levels and factor V molecules, showed hyperhomocysteinemia (51 and 30 micromol/l, respectively). Four other members of the family had the combined antithrombin/factor V Leiden defect and two of them had thrombosis. The common A223V mutation in the methylenetetrahydrofolate reductase gene, responsible for the thermolabile variant of the enzyme, was found to be heterozygous in the proposita; the two sisters were homozygous and heterozygous, respectively. The heterozygous sister also had a high titre of antiphospholipid antibodies (85 units of immunoglobulin G antiphospholipid antibody/ml). Furthermore, low plasma folate levels were found in the three hyperhomocysteinemic subjects of the family. This family with several prothrombotic defects is a clear example of the polyfactorial nature of thrombophilia.
Adult↗
Resistance to activated protein C and low levels of protein S activity in nine thrombophilic families: a correct diagnosis.
In order to define the thrombophilic conditions related to activated protein C resistance (APC-R) and protein S (PS) deficiency and to detect the possible combination of these defects, we studied nine unrelated patients selected because of low anticoagulant response to APC and reduced PS activity with at least one first degree relative having the same coagulation feature. The mean APC ratio was 0.64 (normal values > 0.80) and range 0.35-0.80. Three of the patients were heterozygous and two were homozygous for the Leiden mutation (FVR506Q); in the remaining four there was no mutation. The mean PS activity was 41.6% and range 32-54 (normal 65-150%). Five of the patients had low PS activity despite normal total and free antigenic levels, and normal activity when measured at higher plasma dilution; these were carrying at least one gene for the Leiden mutation. In the remaining four patients the crossed-immunoelectrophoresis and the Western-blotting analysis showed a type I PS deficiency confirmed by the familial restriction fragment length polymorphism analysis. Thus, four families were diagnosed with the type I PS defect and five with congenital APC-R. No combined PS/FV Leiden or type II PS defect was found. The only defect found was in the anticoagulant PC pathway. We therefore designed a procedure to diagnose thrombophilic conditions related to this pathway. This study indicates that a specific methodological approach must be used to accurately characterize APC-R and PS deficiency and that care is necessary to avoid the possibility of misdiagnosis.
Blotting, Western↗
A novel mutation (Leu817Pro) causing type 2A von Willebrand disease.
We studied a patient affected by von Willebrand disease type 2A who experienced several mild bleeding episodes and was characterized by markedly reduced haemostatic parameters. In the exon 28 of von Willebrand factor (vWF) gene a T to C transition at nucleotide 8680, resulting in the missense mutation Leu817Pro, was found in the heterozygous form in the patient and in two affected relatives. As suggested by the presence in platelets of a complete spectrum of vWF multimers as well as by the increased vWF antigen levels and improved haemostasis after DDAVP treatment, the mutation is compatible with normal multimerization, and could be responsible for a reduced stability or an impaired physiological secretion of vWF.
Base Sequence↗
A photometric method for the dosage of factor XIII applied to the study of chronic hepatopathies.
The photometric method of Fickenscher et al. for the determination of factor XIII (FXIII) activity has been used in the study of 35 patients with severe chronic hepatopathy, in comparison with 25 normal subjects. The FXIII proteic fractions a and b were determined by quantitative immuno-electrophoresis after Laurell. The plasmatic FXIII activity, as well as the proteic fractions a and b, were significantly reduced in hepatopatic patients, in comparison to controls, and proportional to the prolongation of prothrombin times. Ratios between functional and immunological levels of FXIII in hepatopatics were similar to those observed in controls. These results confirm the involvement of fibrin stabilization deficiency in the coagulation defect of severe chronic hepatopathies. The correlations between functional and antigenic values are in agreement with the hepatic origin of FXIII. The method of Fickenscher has been proved to be rapid and simple, and it may be useful in the routine study of hepatopathies, for a better knowledge of the role of FXIII deficiency in the complex coagulopathy of liver diseases, as well as of other acquired FXIII deficiencies.
Adult↗
Molecular defects in CRM+ factor VII deficiencies: modelling of missense mutations in the catalytic domain of FVII.
The molecular defects causing CRM+ factor VII deficiency were investigated in seven unrelated subjects and several members of their families. Four missense mutations located in the catalytic domain of factor VII were found. The previously reported 304Arg-->Gln substitution was present in the homozygous and heterozygous forms, with different polymorphic haplotypes, thus demonstrating that it is recurrent and frequent in the Italian population. The 310Cys-->Phe substitution was found in the homozygous form and in the compound heterozygous condition with the nonsense mutation 356Trp-->stop. Two missense mutations, 298Met-->Ile and 342Gly-->Arg, were found in the homozygous and in the heterozygous condition respectively. Molecular heterogeneity was further increased by finding of the 353Arg-->Gln polymorphism in the doubly heterozygous condition with the 304 and 342 mutations. Plausible explanations for loss of FVII function were found by inspecting a model of the serine protease domain of factor VIIa. Inefficient activation of the catalytic site is predicted for 298Met-->Ile. 342Gly-->Arg would directly distort the geometry of the 'oxyanion hole' preventing formation of a substrate enzyme intermediate. 310Cys-->Phe is predicted to have an adverse effect on tissue factor interaction. These mutations point to important regions of the factor VII molecule.
Antigens↗
In-frame deletion of von Willebrand factor A domains in a dominant type of von Willebrand disease.
von Willebrand disease (vWD), the most common inherited bleeding disorder in humans, is very heterogeneous and has been classified into several subtypes. Missense mutations have been found to be responsible for the dominant type II vWD, characterized by qualitative abnormalities affecting von Willebrand factor (vWF) function. The breakpoints of a heterozygous vWF gene deletion (31 Kb), occurring 'de novo' in a patient with a variant of type II vWD, were localized to introns 25 and 34 and sequenced. An Alu repeat in intron 25 was interrupted between the transcriptional boxes A and B. The new junction present in the abnormal von Willebrand factor mRNA was sequenced after reverse transcription of platelet RNA. The codon 1104 (Cys) is followed in frame by the mutated codon 1926 (Cys to Arg), thus removing the complete A domains, found in a wide variety of genes and characterized by independent assembly 'in vitro'. We propose that the abnormal vWF, which carries intact protein domains responsible for vWF dimer and multimer formation, makes ineffective interactions with the normal molecules in the biosynthetic process, causing the dominant type II phenotype through a novel mechanism.
Base Sequence↗
Piezoelectric extracorporeal shock wave lithotripsy in 93 patients with gallstones.
Ninety-three patients with gallstones were selected for extracorporeal shock wave lithotripsy (ESWL) with a piezoelectric device (EDAP LT-OI) to verify the efficacy and safety of this technique. Neuroleptoanalgesia with intravenous diazepam and phentanyl was performed in almost all patients. The treatment was combined with adjuvant litholytic therapy using oral ursodeoxycholic acid. Follow-up period was nine months. Piezoelectric ESWL was able to disintegrate radiolucent gallstones in 97.9% of cases. By the ninth month 68 patients (73.1%) were stone-free. Best results were obtained with single stones smaller than 20 mm. After ESWL, surgical cholecystectomy was necessary in 2.1% of cases. This study confirms the efficacy and safety of piezoelectric extracorporeal shock wave lithotripsy combined with ursodeoxycholic acid adjuvant therapy for selected cases of gallstone disease.
Cholelithiasis↗
Rapid detection of a protein C gene mutation present in the asymptomatic and not in the thrombosis-prone lineage.
The presence of mutations in the serine protease domain of protein C was investigated by temperature gradient gel electrophoresis of PCR products in five patients with protein C deficiency and thrombosis. Molecules with an altered melting behaviour were detected in one subject with a history of venous and arterial thrombosis. Direct sequencing showed that a G deletion, present in the heterozygous state, caused a reading frame shift at Trp 300 and subsequently a premature termination at the codon 335. The resulting suppression of the protein C catalytic function explains the reduction of protease activity to half. In addition the mutation caused a reduction of the antigen level in plasma. Temperature gradient gel electrophoresis enabled the rapid detection of the gene alteration in the family of the propositus. Several members of the paternal lineage had had severe thrombotic episodes. Unexpectedly the mutation was found to be inherited from the clinically asymptomatic maternal lineage, thus suggesting that an additional unknown defect from the paternal lineage is present in the thrombosis-prone propositus.
Adult↗
A de novo and heterozygous gene deletion causing a variant of von Willebrand disease.
An abnormal von Willebrand factor (vWF) gene restriction pattern has been found in a patient with von Willebrand disease. Because this gene alteration is not present in his parents or in 50 normal and 25 affected subjects, and the restriction fragment length polymorphism haplotypes are inherited normally in the patient's family, we suggest that a de novo mutation is present. Bands with reduced intensity and additional fragments, observed in several restriction digests, hybridize with noncontiguous copy DNA (cDNA) portions, thus indicating the presence of a heterozygous gene deletion. The deletion removes a genomic region containing at least codons 1147 through 1854 and corresponding to the D3-A3 homologous protein domains. The extent of the vWF pseudogene on chromosome 22 is roughly similar to that of the deleted area. However, the pseudogenic nature of the deletion is excluded by the mapping of bands with reduced intensity in the patient to the true vWF gene. The vWF antigen levels are one fourth of normal and ristocetin cofactor activity is severely impaired. The reduction of high molecular weight multimers in plasma and platelets and the altered triplet morphology are compatible with the presence of a dominant variant of type II von Willebrand disease.
Bleeding Time↗
[Neonatal screening and follow-up of congenital hip luxation using echography. Review of the literature and personal contribution on 1421 newborns].
US screening for hip dysplasia was performed on 1421 full-term newborns. The study was aimed at: 1) evaluating US feasibility in an unselected maternity ward population; 2) determining the frequency of the different types of hips, and correlating ours with literature data; 3) evaluating the efficacy of both an early prevention and treatment. All US examinations were performed within the first week of life and the 2842 hips classified according to Graf. At birth, normal hips (Ia, Ib) were 2064 (72.6%) (group I); physiologically immature hips (IIa) were 721 (25.4%) (group II); pathological hips (group III) were: 43 (1.5%) IIc, 8 (0.3%) IId, 6 (0.2%) III. Hips in group B were checked at 3 months: 502 were normal, 51 were type IIb, and 1 was type IId: the latter 52 hips were treated and normalized in the following months. Hips in group C (types IIc, IId, and III = 57 hips) were treated and checked every seventh week until normalization. Our experience confirms US value in the evaluation of hip dysplasia in the newborn. In our opinion, the use of this method should be encouraged, although US screening of all newborns remains controversial on a cost-benefit ratio. Multicentric studies will better define US sensitivity, specificity and reliability. The correlation of our results with literature data was difficult, because study populations are not always homogeneous. As for therapy, we found the plastic splint very effective and easy to use. In 2 cases, Milgram devices were used for a few months.
Female↗
Capsaicin-sensitive tachykinin-like immunoreactivity in the thymus of rats and guinea-pigs.
Capsaicin-sensitive, substance P-like immunoreactivity (SP-LI) has been detected recently in rat thymus. Other tachykinins are frequently present with SP. In the present study, tachykinin-like immunoreactivity (TK-LI) was measured in guinea-pig, rat, mouse and hamster thymus with the amount detectable being greatest in guinea-pig, less in rat and least in mouse; it was not detectable in hamsters. In guinea-pig and rat thymus, but not in mouse, TK-LI was markedly reduced by pretreatment with capsaicin. TK-LI levels correlated significantly with those of SP-LI in both guinea-pig and rat thymus. High-performance liquid chromatography (HPLC) fractions considered to represent neurokinin A, eledoisin and neuropeptide K were present in guinea-pig thymus but only the first two were present in rat thymus.
Animals↗
von Willebrand disease investigated by two novel RFLPs.
Two partial cDNAs for von Willebrand factor (vWF) were used to investigate gene lesions and restriction fragment length polymorphisms (RFLPs) in vW disease (vWd) and normal controls. No gene alteration was detected but two TaqI RFLPs, likely to be intronic and originating from point mutations, were found in the 3' part of vWF gene. The two TaqI RFLPs, identified by the same probe, are informative in approximately 50% of the subjects. Used in combination with two other known RFLPs, they define several haplotypes similarly distributed in vWd and normals. Linkage disequilibrium between loci identified by the RFLPs is present. In a family study the RFLP patterns demonstrate homozygosity for the affected vWF gene in a severe (type III) patient and identify several heterozygous subjects. The RFLPs analysis has been related to the haemostatic values and multimer distribution. In two of the four unrelated patients with severe vWd examined the RFLPs study indicates double heterozygosity for the affected vWF genes.
Genetic Linkage↗