St. George's Hospital questionnaire (St. George's Respiratory Questionnaire) as an instrument for quality of life assessment in respiratory tract diseases

St. George's Respiratory Questionnaire (SGRQ) is one of the main measures of the quality of life in patients with pulmonary diseases. We review the literature concentrating the use of SGRQ in patients with asthma, chronic obstructive pulmonary disease, bronchectases, interstitial lung disease and in adult respiratory distress syndrome (ARSD).     

The long-term outcome of mitral valve repair for mitral valve prolapse

The rationale of early surgery for severe chronic mitral regurgitation (MR) due to mitral valve prolapse (MVP) has been developed over the past decade on the basis of the understanding of the natural history of this disease and the predictors of outcomes after surgical correction of MR. The important decrease in operative mortality associated with the advancements in myocardial preservation, and more importantly the improved reparability of the myxomatous mitral valve, were an additional incentive to develop the concept of early surgery. Previous studies showed that mitral valve repair offers a survival advantage at short- and 10-year follow-up, and therefore suggested that it should be the treatment of choice for severe MR due to MVP. Moreover, very recent data provided new insight on the very long-term follow up, ie, beyond the usual first 10 years in which the initial survival benefit of repair may be negated by a late deterioration.     

A case of fugitive acromegaly, initially presented as invasive prolactinoma

Fugitive acromegaly is most commonly caused by pituitary acidophil stem cell adenomas, and is characterized by a relatively short clinical history, a large and locally invasive tumor, and relatively low hormonal activity. Here, we report an unusual case of fugitive acromegaly that initially presented as invasive prolactinoma. A 48-year-old man with a huge pituitary mass extending to the suprasellar area was referred to our hospital in December 2007. He had undergone transsphenoidal surgery in November 1999 because of a large invasive prolactinoma. The tumor had grown progressively, despite therapy with dopamine agonists. Subtle features of acromegaly were noted and serum IGF-1 levels were high (733 ng/ml). An oral glucose tolerance test revealed that basal and nadir levels of growth hormone (GH) were 1.56 and 1 ng/ml, respectively. As a therapeutic trial, long-acting octreotide (20 mg IM, monthly) was added, and the tumor size markedly reduced within 6 months on magnetic resonance imaging examination. Immunohistochemical staining of the tumor tissue obtained at the surgery in 1999 showed positive staining for GH and prolactin (PRL). Double immunofluorescence staining showed a mixed positivity for GH and PRL in the majority of tumor cells; however, the two hormones colocalized in a minority of tumor cells, indicating that the tumor was composed of three different cell types (GH, PRL, and GH/PRL). The diagnosis of fugitive acromegaly was initially overlooked in this patient because of normal serum GH levels and a lack of acromegalic features, although histological evidence for GH production was present. IGF-1 determinations would be helpful for the diagnosis of fugitive acromegaly.     

Abdominal computed tomography findings of malaria infection with Plasmodium vivax

Abdominal computed tomography (CT) findings of malaria are not well-known even though malaria is a serious infectious disease. To identify abdominal CT findings, we selected 34 of 405 patients who had a positive peripheral blood smear for Plasmodium vivax and had underwent abdominal CT as the malaria group. We also selected 80 patients who had fever and a negative peripheral blood smear as the control group and 120 healthy people as the normal group. We reviewed and analyzed their medical records and CT findings retrospectively. The mean spleen and liver length were significantly larger in the malaria group and the incidence of splenomegaly, splenic focal low attenuation, and spontaneous splenic rupture were much higher in the malaria group (P < 0.05). Although abdominal CT is not an indispensable tool for diagnosis, these CT findings will help in the diagnosis of malaria in patients with fever.     

Influence of insertion-deletion polymorphism of the angiotensin converting enzyme gene on left ventricular hypertrophy in patients with aortic stenosis--differences in men and women

The role of different parameters (including genetic factors) on the timing and extend of left ventricle hypertrophy in patients with aortic stenosis is not defined. In our study we analyze the influence of clinical, echocardiographic parameters and I/D polymorphism of the angiotensin converting enzyme gene on the left ventricle hypertrophy (left ventricle mass index) in this group of patients. The study was done with the group of 302 pts with aortic stenosis--120 women and 182 men; mean age 58 +/- 11 yrs. Stepwise (backward) regression was used to assess the influence of the analyzed parameters (age, gender, history of hypertension, EF, MGA, presence of significant coronary artery disease and I/D ACE polymorphism) on the LVH in the all pts and in the women and the men separately. In the whole group the LVMI depends on EF (t = -6.5; p = 0.0001--higher LVMI in lower EF), MGA (t = 3.9; p = 0.0001--higher LVMI in higher MGA) and gender (t = 2.8; p = 0.005--higher LVMI in men). In women LVMI was related with EF (t = -3.6; p = 0.001--higher LVMI in lower EF), age (t = 2.9; p = 0.004--higher LVMI in older pts) and MGA (t = 2.5; p = 0.013--higher LVMI in higher MGA). In men the LVMI depends on EF (t = -4.8; p = 0.0001--higher LVMI in lower EF) and MGA (t = 1.98; p = 0.049--higher LVMI in higher MGA). Significant relationship between LVMI and results of I/D ACE polymorphism was observed both in women and men. I/D polymorphism relationship with LVMI was divergent in these 2 groups--association of higher LVMI with lack of DD type of polymorphism in women and presence of DD polymorphism in men. CONCLUSIONS: 1. Left ventricle hypertrophy in pts aortic stenosis is higher in men than in women. 2. In women left ventricle hypertrophy is related with ejection fraction, maximal aortic gradient, age and I/D ACE polymorphism; in men it is related to EF, MGA and I/D ACE polymorphism. 3. The influence of I/D ACE polymorphism on the left ventricle hypertrophy is divergent in women and men--in women related to the lack of DD polymorphism, in men related to the presence of DD polymorphism.     

Novel risk factors for peripheral arterial disease in young women

PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.     

Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia

The analysis of total plasma DNA and the monitoring of leukemic clone-specific immunoglobulin and/or T-cell receptor gene rearrangements for the evaluation of minimal residual disease (MRD) in the plasma may be useful tools for prognostic purposes or for early detection of subclinical disease recurrence in children with acute lymphoblastic leukemia (ALL). The aim of this paper is to establish reference ranges for total plasma DNA concentrations and to test the feasibility of MRD measurements employing plasma DNA from children with ALL by using real-time quantitative (RQ)-PCR. Despite wide inter-individual variation, the median concentrations of total plasma DNA for 12 healthy donors (57 ng/ml), 21 children with ALL after day 4 of treatment initiation (62 ng/ml) and 13 children with other malignancies (76 ng/ml) were similar. However, ALL patients had significantly higher concentrations at diagnosis (277 ng/ml) and on treatment day 3 (248 ng/ml) before returning to normal afterwards. Early plasma DNA MRD kinetics could be established for 15 ALL patients and showed good concordance with bone marrow MRD. Plasma DNA was higher in children with ALL at diagnosis but returned to normal within the first four treatment days. Despite low concentrations of DNA, it is feasible to measure MRD kinetics in plasma DNA during ALL induction therapy by adapted real-time PCR methodologies. This work was supported by the Deutsche Krebshilfe (Bonn, Germany) and the Leukemia Research Foundation (Chicago, IL, USA).     

Integrin alpha V polymorphisms and haplotypes in a Korean population are associated with susceptibility to chronic hepatitis and hepatocellular carcinoma

Background/Aims: Integrins are cell surface receptors for extracellular matrix (ECM) proteins that initiate signalling pathways that modulate proliferation, survival, invasion or metastasis. Consequently, integrins are potential targets for the treatment of cancer. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in integrin α_V (ITGAV) in a Korean population were associated with chronic hepatitis B virus (HBV) infection and HBV‐infected hepatocellular carcinoma (HCC). Patients and Methods: Thirteen ITGAV SNPs in 111 cases of chronic HBV infection, 86 cases of HBV‐infected HCC and 107 cases of acute self‐limited HBV infection were genotyped using Illumina's Sentrix array matrix (SAM) chip. Results: The ITGAV intron SNPs rs9333289 and rs11685758, the 3′‐untranslated region SNP rs1839123 and haplotype 3 (T–T–A) were associated with enhanced susceptibility to HBV‐infected HCC (OR=1.75–2.42; P=0.02–0.05), while the intron SNP rs2290083 was associated with both chronic infection and HBV‐infected HCC (OR=1.73–2.01; P=0.01–0.04). In addition, both rs2290083 and ht1 (C–C–G) were associated with the age at which chronic infection occurred, as determined by Cox relative hazard analysis (RH=1.39–1.62, P=0.04–0.01) Conclusion: ITGAV SNPs and haplotypes may be genetic factors that increase the susceptibility of Koreans to chronic HBV infection and HBV‐infected HCC.     

The anticoagulant activation of antithrombin by heparin

Antithrombin, a plasma serpin, is relatively inactive as an inhibitor of the coagulation proteases until it binds to the heparan side chains that line the microvasculature. The binding specifically occurs to a core pentasaccharide present both in the heparans and in their therapeutic derivative heparin. The accompanying conformational change of antithrombin is revealed in a 2.9-Å structure of a dimer of latent and active antithrombins, each in complex with the high-affinity pentasaccharide. Inhibitory activation results from a shift in the main sheet of the molecule from a partially six-stranded to a five-stranded form, with extrusion of the reactive center loop to give a more exposed orientation. There is a tilting and elongation of helix D with the formation of a 2-turn helix P between the C and D helices. Concomitant conformational changes at the heparin binding site explain both the initial tight binding of antithrombin to the heparans and the subsequent release of the antithrombin–protease complex into the circulation. The pentasaccharide binds by hydrogen bonding of its sulfates and carboxylates to Arg-129 and Lys-125 in the D-helix, to Arg-46 and Arg-47 in the A-helix, to Lys-114 and Glu-113 in the P-helix, and to Lys-11 and Arg-13 in a cleft formed by the amino terminus. This clear definition of the binding site will provide a structural basis for developing heparin analogues that are more specific toward their intended target antithrombin and therefore less likely to exhibit side effects.