Does reducing radiation levels for procedures affect image quality and radiation to proceduralists? A double-blinded randomised study of two protocols.

AIM: To evaluate the ultra-lose dose imaging protocol (ULDP), compared to the standard low-dose imaging protocol (LDP), which are used for haemodialysis access, in terms of radiation exposure and image quality. MATERIAL AND METHODS: This was a single-centre, institutional review board-approved, prospective, double-blinded randomised controlled study to compare radiation exposure and image quality of the ULDP and LDP. Ten proceduralists, two radiographers, and 11 nurses were enrolled. Radiation exposure during 80 procedures (40 angioplasties and 40 thrombolysis) was recorded (direct radiation to patients from protocol report and scattered radiation to participants from the RaySafe i2 real-time dosimetry system). Baseline characteristics of procedure were recorded. Image quality was assessed subjectively using questionnaires based on the five-point Likert scale after each procedure. RESULTS: Compared with LDP, the use of ULDP was associated with a significantly lower rate of radiation exposure to proceduralists, patients, and scrub nurses (0.506±0.430 versus 0.847±0.965 µSv/s, p=0.044; 0.571±1.284 versus 1.284±1.007 mGy/s, p<0.001; and 0.052±0.071 versus 0.141±0.185 µSv/s, p=0.005, respectively). No significant difference in image quality or duration of procedure was observed (all p values >0.05). CONCLUSION: Compared with LDP, the use of ULDP was associated with a significantly lower rate of radiation exposure to proceduralists, patients, and scrub nurses without compromising the image quality or duration of procedure.

[Association between single nucleotide polymorphism in promoter region of SIRT1 gene and senile degenerative heart valvular disease].

Objective: To investigate the correlation between single nucleotide polymorphisms (SNPs) of SIRT1 gene promoter sequence and senile degenerative heart valvular disease (SDHVD). Methods: A total of 236 SDHVD patients and 285 healthy controls who visited the Affiliated Hospital of Jining Medical University between February 2012 and October 2016 were enrolled. SNPs of SIRT1 gene promoter were detected by Sanger sequencing. Typing and correlation were analyzed by χ(2) test and Logistic regression analysis. Haplotype and linkage disequilibrium were analyzed by Haploview4.2 software and SHEsis online software. The effect of SNPs on the binding of transcription factors to SIRT1 gene promoter was analyzed by electrophoretic mobility shift assay(EMSA). The transcription factors affected by SNPs were predicted by Transfac online software. Results: The frequency distribution of GG genotype of rs3740051 in the SDHVD group was significantly higher than that in the control group (χ(2)=4.855, P=0.028). There was a correlation between GG genotype of the rs3740051 and SDHVD. After adjusting for age, the risk of SDHVD in the carrier of GG genotype was 3.079 times higher than that of AA genotype(OR=3.079, 95%CI: 1.156-8.201, P=0.024). The five SNPs (rs3740051, rs932658, rs35995735, rs3740053 and rs2394443) showed strong linkage disequilibrium(D'>0.8). The haplotype analysis of the five SNPs (haplotype frequency<0 was ignored in the analysis) showed that 11 haplotypes (P<0.05) were formed, and the frequency of *A**C, AA**C, *AG*C, AAG*C, AA*AC, *AGAC and AAGAC in SDHVD group were significantly higher than that in control group (P<0.05, OR>1, 95%CI does not contains 1). EMSA showed that the color of the binding bands incubated by wild type probe and nucleoprotein was darker than that incubated by DNA sequence variation probe and nucleoprotein. Conclusion: The GG genotype of rs3740051 is associated with SDHVD and may be a risk genotype for SDHVD. The haplotype AC (across rs932658 and rs2394443) may be a dangerous haplotype of SDHVD. rs3740051 may affect the occurrence and development of SDHVD by interfering with the binding of FOXC protein to SIRT1 gene promoter.

Mechanically-induced osteophyte in the rat knee.

OBJECTIVES: Osteophytes are common anatomical signs of advanced osteoarthritis. It remains unclear whether they develop from physio-molecular, and/or mechanical stimuli. This study examined the effects of mechanical impact on the knee joint periosteum leading to osteophyte formation. DESIGN: Eighteen mature rats received one single impact load of 53 N (30 MPa) to the periosteum of the experimental medial femoral condyles. Contralateral knees were used as controls. Animals were sacrificed at 24 h, 3, 6 and 9 weeks post-impact. Distal femurs were harvested and prepared for histology. Hematoxylin and Eosin, and Masson's trichrome stained slides were examined by light microscopy. Nuclear density was quantified to assess the tissue reaction. RESULTS: 24 h: The synovium membrane, fibrous and cambium periosteum were damaged. Blood infiltration pooled in the impacted medial collateral ligament (MCL) region. Week 3: A cartilaginous tissue spur, chondrophyte, was found in every rat at the impacted site of the MCL. Chondrophytes were composed of fibrocartilage and cartilage matrix, with signs of cartilage mineralization and remodelling activity. Week 6: Chondrophytes presented signs of more advanced mineralisation, recognized as osteophytes. Week 9: Osteophytes appeared to be more mineralized with almost no cartilage tissue. CONCLUSIONS: Osteophytes can be induced with a single mechanical impact applied to the periosteum in rat knees. These data indicate that a moderate trauma to the periosteal layer of the joint may play a role in osteophyte development.

Low efficacy of delthamethrin-treated net against Singapore Aedes aegypti is associated with kdr-type resistance.

There has been a worldwide surge in the number and severity of dengue in the past decades. In Singapore, relentless vector control efforts have been put in to control the disease since the 1960's. Space spraying, fogging, chemical treatment and source reduction are some commonly used methodologies for controlling its vectors, particularly Aedes aegypti. Here, as we explored the use of a commercially available delthamethrin-treated net as an alternative strategy and the efficacy of the treated net was found to be limited. Through bioassays and molecular studies, the failure of the treated net to render high mortality rate was found to be associated with the knockdown resistance (kdr) mutation. This is the first report of kdr- mutations in Singapore's Ae. aegypti. At least one point mutation, either homozygous or heterozygous, at amino acid residue V1016G of DIIS6 or F1269C of DIIIS6 was detected in 93% of field strains of Ae. aegypti. Various permutations of wild type and mutant amino acids of the four alleles were found to result in varying degree of survival rate among local field Ae. aegypti when exposed to the deltamethrin treated net. Together with the association of higher survival rate with the presence of both V1016G and F1269C, the data suggest the role of these mutations in the resistance to the deltamethrin. The high prevalence of these mutations were confirmed in a country wide survey where 70% and 72% of the 201 Ae. aegypti analysed possessed the mutations at residues 1016 and 1269 respectively. The highest mutated frequency combination was found to be heterozygous alleles (VG/FC) at both residues 1016 and 1269 (37.8%), followed by homozygous mutation at allele 1269 (24.4%) and homozygous mutation at allele 1016 (22.9%). The kdr- type of resistance among the vector is likely to undermine the effectiveness of pyrethroids treated materials against these mosquitoes.

Low efficacy of delthamethrin-treated net against Singapore Aedes aegypti is associated with kdr-type resistance

There has been a worldwide surge in the number and severity of dengue in the past decades. In Singapore, relentless vector control efforts have been put in to control the disease since the 1960’s. Space spraying, fogging, chemical treatment and source reduction are some commonly used methodologies for controlling its vectors, particularly Aedes aegypti. Here, as we explored the use of a commercially available delthamethrin-treated net as an alternative strategy and the efficacy of the treated net was found to be limited. Through bioassays and molecular studies, the failure of the treated net to render high mortality rate was found to be associated with the knockdown resistance (kdr) mutation. This is the first report of kdr- mutations in Singapore’s Ae. aegypti. At least one point mutation, either homozygous or heterozygous, at amino acid residue V1016G of DIIS6 or F1269C of DIIIS6 was detected in 93% of field strains of Ae. aegypti. Various permutations of wild type and mutant amino acids of the four alleles were found to result in varying degree of survival rate among local field Ae. aegypti when exposed to the deltamethrin treated net. Together with the association of higher survival rate with the presence of both V1016G and F1269C, the data suggest the role of these mutations in the resistance to the deltamethrin. The high prevalence of these mutations were confirmed in a country wide survey where 70% and 72% of the 201 Ae. aegypti analysed possessed the mutations at residues 1016 and 1269 respectively. The highest mutated frequency combination was found to be heterozygous alleles (VG/FC) at both residues 1016 and 1269 (37.8%), followed by homozygous mutation at allele 1269 (24.4%) and homozygous mutation at allele 1016 (22.9%). The kdr- type of resistance among the vector is likely to undermine the effectiveness of pyrethroids treated materials against these mosquitoes.

The effect of moving point of contact stimulation on chondrocyte gene expression and localization in tissue engineered constructs.

Tissue engineering is a promising approach for articular cartilage repair. However, using current technologies, the developed engineered constructs generally do not possess an organized superficial layer, which contributes to the tissue's durability and unique mechanical properties. In this study, we investigated the efficacy of applying a moving point of contract-type stimulation (MPS) to stimulate the production of a superficial-like layer in the engineered constructs. MPS was applied to chondrocyte-agarose hydrogels at a frequency of 0.5, 1 or 2 Hz, under a constant compressive load of 10 mN for durations between 5 and 60 min over 3 consecutive days. Expression and localization of superficial zone constituents was conducted by qRT-PCR and in situ hybridization. Finite element modeling was also constructed to gain insight into the relationship between the applied stimulus and superficial zone constituent expression. Gene expression of superficial zone markers were affected in a frequency dependent manner with a physiologic frequency of 1 Hz producing maximal expression of PRG4, biglycan, decorin and collagen II. In situ hybridization revealed that localization of these markers predominantly occurred at 500-1000 µm below the construct surface which correlated to sub-surface strains between 10 and 25% as determined by finite element modeling. These results indicate that while mechanical stimuli can be used to enhance the expression of superficial zone constituents in engineered cartilage constructs, the resultant subsurface loading is a critical factor for localizing expression. Future studies will investigate altering the applied stimulus to further localize superficial zone constituent expression at the construct surface.

Noninvasive investigation of asymmetrically conjoined tripus twins with features of rachipagus, parapagus dicephalus, and cephalopagus.

A hypothetical mechanism for conjoined twinning postulated by Spencer ([2003] Developmental Malformations and Clinical Implications, Baltimore: Johns Hopkins University Press, p 1-476) suggests that, after separation, monovular twins fuse in one of eight predictable homologous sites. The tripus fetal specimen under study embodies characteristics of three types therefore preventing it from classification into a simple variant of any one of the eight twin types described by Spencer. The aim of this study was to reveal internal structural anomalies of the fetal specimen by using magnetic resonance imaging and computerized tomography. Dorsally appended to the primary twin is a secondary head mass (brain tissue and ocular globe) and two spinal columns converging at T4/T5, suggesting rachipagus twinning. The ventral orientation of the secondary twin's (right lateral) lower limb suggests parapagus twinning. The caudal divergence of the spinal columns and the presence of a secondary hemipelvis, separate from the primary pelvis, suggest cephalopagus twinning. Measurements of the long bones indicate a gestational age of ∼20-23 weeks. Secondary malformations of the primary fetal body include anencephaly, cleft palate, renal agenesis, decreased left ventricular outflow, and a prematurely terminating descending aorta. This study demonstrates the possibility of using current imaging techniques to study very old, formalin-preserved human material for documentation and scientific discussion without destroying the specimen, thus keeping it intact for posterity.

A potential role for the endothelin ETA receptor in salt-sensitive hypertension of the proANP gene-disrupted mouse.

We have previously shown that the partial disruption of the gene for atrial natriuretic peptide (ANP) results in a salt-sensitive phenotype. The present study examined the possibility that alterations in either the ANP natriuretic pathway or endothelin (ET) system in the kidney of the salt-challenged ANP +/- mouse was responsible for its salt-sensitive phenotype. Plasma ANP levels and renal cGMP activity were increased in response to a salt load in both ANP +/+ and +/- mice. However, the mRNA expression of proANP was found to be increased only in the ANP +/- kidney along with its guanylyl cyclase-linked receptor, NPRA; the upregulation of NPRA mRNA was limited to the renal medulla. This suggests that the renal ANP pathway remains capable of responding to a salt load in the ANP +/- animal, but may be compensating for other dysfunctional pathways. We also report a significant increase in renal ET-1 mRNA and ETA receptor protein expression in medulla and cortex of the salt-treated, ANP +/- mouse, but not its wild-type counterpart. In fact, ETA expression decreased in the renal cortex of the ANP +/+ salt-treated animal. The ETB receptor expression was not affected by diet in either genotype. We hypothesize that the salt-sensitive hypertension in the ANP +/- mouse is exacerbated, and possibly driven by the vasoconstrictive effects resulting from an upregulated ET-1/ETA pathway.

The effect of asbestosis on lung cancer risk beyond the dose related effect of asbestos alone.

AIMS: To determine if the presence of asbestosis is a prerequisite for lung cancer in subjects with known exposure to blue asbestos (crocidolite). METHODS: Former workers and residents of Wittenoom with known amounts of asbestos exposure (duration, intensity, and time since first exposure), current chest x ray and smoking information, participating in a cancer prevention programme (n = 1988) were studied. The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was examined for radiographic evidence of asbestosis according to the UICC (ILO) classification. Cox proportional hazards modelling was used to relate asbestosis, asbestos exposure, and lung cancer. RESULTS: Between 1990 and 2002 there were 58 cases of lung cancer. Thirty six per cent of cases had radiographic evidence of asbestosis compared to 12% of study participants. Smoking status was the strongest predictor of lung cancer, with current smokers (OR = 26.5, 95% CI 3.5 to 198) having the greatest risk. Radiographic asbestosis (OR = 1.94, 95% CI 1.09 to 3.46) and asbestos exposure (OR = 1.21 per f/ml-year, 95% CI 1.02 to 1.42) were significantly associated with an increased risk of lung cancer. There was an increased risk of lung cancer with increasing exposure in those without asbestosis. CONCLUSION: In this cohort of former workers and residents of Wittenoom, asbestosis is not a mandatory precursor for asbestos related lung cancer. These findings support the hypothesis that it is the asbestos fibres per se that cause lung cancer, which can develop with or without the presence of asbestosis.

The additional risk of malignant mesothelioma in former workers and residents of Wittenoom with benign pleural disease or asbestosis.

AIMS: To examine the hypothesis that people with benign pleural disease or asbestosis have an increased risk of malignant mesothelioma beyond that attributable to their degree of asbestos exposure. METHODS: Former workers and residents of the crocidolite mining and milling town of Wittenoom are participating in a cancer prevention programme (n = 1988). The first plain chest radiograph taken at the time of recruitment into the cancer prevention programme was read for evidence of benign pleural disease and asbestosis, using the UICC classification. Crocidolite exposure of former workers was derived from employment records and records of dust measurements performed during the operation of the asbestos mine and mill between 1943 and 1966. Based on fibre counts, exposure for former residents was determined using duration of residence and period of residence (before and after a new mill was commissioned in 1957) and interpolation from periodic hygienic measures undertaken from personal monitors between 1966 and 1992. Cox proportional hazards modelling was used to relate benign pleural disease, asbestosis, asbestos exposure, and mesothelioma. RESULTS: Between 1990 and 2002, there were 76 cases of mesothelioma (56 of the pleura and 20 of the peritoneum). Cases had more radiographic evidence of (all) benign pleural disease, pleural thickening, blunt/obliterated costophrenic angle, and asbestosis than non-cases. Adjusting for time since first exposure (log years), cumulative exposure (log f/ml-years), and age at the start of the programme, pleural thickening (OR = 3.1, 95% CI 1.2 to 7.6) and asbestosis (OR = 3.3, 95% CI 1.3 to 8.6) were associated with an increased risk of peritoneal mesothelioma. There was no increased risk for pleural mesothelioma. CONCLUSION: The presence of benign pleural disease, in particular pleural thickening, and asbestosis appears to increase the risk of mesothelioma of the peritoneum, but not of the pleura beyond that attributable to indices of asbestos exposure in this cohort of subjects exposed to crocidolite.

Radiographic (ILO) readings predict arterial oxygen desaturation during exercise in subjects with asbestosis.

BACKGROUND: Exercise impairment is common in subjects with asbestosis. Arterial oxygen desaturation during exercise is an important contributor to exercise limitation. The International Labour Office (ILO) classification of plain chest radiographs correlates with resting pulmonary function, but its value in predicting abnormal ventilatory responses to exercise, including desaturation, has not been explored. AIMS: To determine in subjects with asbestosis (1) if radiographic profusion scores and the extent of small irregular shadows on plain chest radiographs correlate with resting lung function and abnormal ventilatory responses to exercise; and (2) if radiographic scores add value to resting lung function tests in predicting abnormal ventilatory responses to exercise. METHODS: Thirty eight male subjects with asbestosis were included. Plain chest radiographs were read according to the ILO classification independently by three observers. All subjects underwent assessment of lung function and an incremental exercise test. RESULTS: Profusion scores and number of affected zones correlated significantly with the percentage predicted values of single breath diffusing capacity (DLCO), forced vital capacity (FVC), and total lung capacity (TLC). Arterial oxygen desaturation occurred in 29% of the subjects. The severity of desaturation correlated significantly with profusion and the number of affected zones. The combined use of number of affected zones, FEV(1)/FVC ratio and DLCO predicted desaturation during exercise with an explained variance of 41%. VO(2)max was significantly related only to DLCO but was not predicted by the ILO score. CONCLUSION: Arterial oxygen desaturation correlated with the profusion and extent of parenchymal abnormality on chest radiographs. The addition of morphological indices to physiological measurements is valuable for predicting oxygen desaturation during exercise but not for VO(2)max. Refinement of the radiographic scoring system and the addition of more sophisticated imaging techniques may further improve the predictive power.

Silicosis compensation in Western Australian gold miners since the introduction of an occupational exposure standard for crystalline silica.

UNLABELLED: Occupational exposure limits for crystalline silica are under review worldwide because of the large numbers of exposed people and, especially, because of the recent International Agency for Research on Cancer classification of silica as a human carcinogen. OBJECTIVES: The aims of this study were to (i) re-examine the incidence of silicosis in Western Australian gold miners and, using estimates of the total population at risk, (ii) estimate the upper confidence limit for the risk of silicosis in Western Australian gold miners since 1974, when the current exposure standard for crystalline silica was implemented. METHODS: Work histories of cases compensated for pneumoconiosis after 1974 were examined. Numbers of workers in the total workforce likely to be exposed to crystalline silica in Western Australia were estimated as the population at risk. RESULTS: There were no cases of compensated silicosis in Western Australian miners whose first dust exposure began during or after 1974. The upper 95% confidence interval for this zero rate was estimated to be 4.8 per 100,000 person-yr. CONCLUSIONS: There have been no compensated cases of silicosis in Western Australia among miners first exposed to crystalline silica after introduction of the current exposure standard. A rate of compensated silicosis higher than five cases per 100,000 person-yr is unlikely.

Investigation of a cyclopic, human, term fetus by use of magnetic resonance imaging (MRI).

Using magnetic resonance imaging (MRI), the internal neural and craniofacial malformations of a cyclopic fetus are described. External facial features were characterized by a tubular proboscis situated above a single eye slit. The brain was recognized as 'pancake' type alobar holoprosencephaly (a condition where the undifferentiated telencephalon partially surrounds a monoventricle). Displacement of some bones that normally contribute to the orbit could be clearly discerned. Absence of neural structures (e.g. falx cerebri, corpus callosum) and missing components of the ethmoid bone indicated a midline deficit. This correlates with proposed theories of cyclopic embryopathy, which suggest that the prechordal plate and the neural crest cells are affected during the third week of gestation in cyclopia.

Expression of B-type natriuretic peptide in atrial natriuretic peptide gene disrupted mice.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are two hormones produced and secreted by the heart to control blood pressure, body fluid homeostasis and electrolyte balance. Each peptide binds to a common family of 3 receptors (GC-A, GC-B and C-receptor) with varying degrees of affinity. The proANP gene disrupted mouse model provides an excellent opportunity to examine the regulation and expression of BNP in the absence ofANP. A new radioimmunoassay (RIA) was developed in order to measure mouse BNP peptide levels in the plasma, atrium and ventricle of the mouse. A detection limit of 3-6 pg/tube was achieved by this assay. Results show that plasma and ventricular level of BNP were unchanged among the three genotypes of mice. However, a significant decrease in the BNP level was noted in the atrium. The homozygous mutant (ANP-/-) had undetectable levels of BNP in the atrium, while the heterozygous (ANP+/-) and wild-type (ANP+/+) mice had 430 and 910 pg/mg in the atrium, respectively. Northern Blot analysis shows the ANP-/- mice has a 40% reduction of BNP mRNA level in the atrium and a 5-fold increase in the ventricle as compared with that of the ANP+/+ mouse. Our data suggest that there is a compensatory response of BNP expression to proANP gene disruption. Despite the changes in the atrial and ventricular tissue mRNA and peptide levels, the plasma BNP level remains unaltered in the ANP-/- mice. We conclude that the inability of BNP to completely compensate for the lack of ANP eventually leads to chronic hypertension in the proANP gene disrupted mice.

Cardiac troponin I is modified in the myocardium of bypass patients.

BACKGROUND: Selective proteolysis of cardiac troponin I (cTnI) is a proposed mechanism of contractile dysfunction in stunned myocardium, and the presence of cTnI degradation products in serum may reflect the functional state of the remaining viable myocardium. However, recent swine and canine studies have not demonstrated stunning-dependent cTnI degradation. METHODS AND RESULTS: To address the universality of cTnI modification, myocardial biopsy samples were obtained from coronary artery bypass patients (n=37) before and 10 minutes after removal of cross-clamp. Analysis of biopsy samples for cTnI by Western blotting revealed a spectrum of modified cTnI products in myocardium both before and after cross-clamp, including degradation products (7 products resulting from differential N- and C-terminal processing) and covalent complexes (3 products). In particular, a 22-kDa cTnI degradation product with C-terminal proteolysis was identified, which may represent an initial ischemia-dependent cTnI modification, similar to cTnI(1-193) observed in stunned rat myocardium. Although no systematic change in amount of modified cTnI was observed, subgroups of patients displayed an increase (n=10, 85+/-5% of cTnI remaining intact before cross-clamp versus 75+/-5% after) or a decrease (n=12, 67+/-5% before versus 78+/-5% after). Electron microscopy demonstrated normal ultrastructure in biopsy samples, which suggests no necrosis was present. In addition, cTnI modification products were observed in serum through a modified SDS-PAGE methodology. CONCLUSIONS: cTnI modification, in particular proteolysis, occurs in myocardium of bypass patients and may play a key role in stunning in some bypass patients.

Increased body mass index is related to apparent circumscribed pleural thickening on plain chest radiographs.

BACKGROUND: Diffuse pleural thickening and pleural plaques are the commonest radiological manifestations of asbestos exposure. Differentiation between subpleural fat and non-calcified pleural plaques is important clinically and medico-legally. This study aims to determine if apparent circumscribed pleural thickening on chest radiographs is related with obesity. METHODS: Surveillance chest x-rays of 693 former asbestos workers were read with the ILO classification. Subjects with costophrenic angle obliteration (n = 57) were analyzed separately. The remaining subjects were subdivided according to their body mass index (BMI): Group 1 < 26 kg/m(2); Group 2 26-30 kg/m(2); Group 3 > 30 kg/m(2). RESULTS: Baseline characteristics, asbestos exposure, and profusion scores were evenly distributed. BMI of > 30 kg/m(2) was associated with a higher prevalence of pleural thickening on CXR (Gp1 = 8.5%; Gp2 = 9.3%; Gp3 = 18.3%). This relationship was strongest in the subgroups with 25-50% of the lateral chest wall involved and pleural thickness of < 10 mm. CONCLUSIONS: Obesity (BMI > 30 kg/m(2)) is related to apparent circumscribed pleural thickening on CXR, especially thin (< 1 cm) shadows covering 25-50% of the lateral chest wall.

Chest pain in asbestos-exposed individuals with benign pleural and parenchymal disease.

Many asbestos-exposed individuals complain of chest pain for which there is no clear explanation. To determine whether chest pain is associated with the presence of benign pleural or parenchymal disease on chest radiograph, we studied 1,280 subjects undergoing surveillance because of prior asbestos exposure at Wittenoom, Western Australia. All subjects completed the Rose questionnaire on chest pain and this revealed 556 subjects (43%) who experienced some chest pain. A posterior-anterior chest radiograph was performed at the same clinic visit and was subsequently graded independently by two experienced readers for diffuse parenchymal disease and pleural disease. Logistic regression models adjusted for sex, age, and cumulative asbestos exposure indicated that the presence of chest pain was significantly associated with the presence of both benign pleural disease and diffuse parenchymal disease. Further analysis after stratification of chest pain into nonanginal and anginal pain showed that there was a significant association between anginal pain and the presence of pleural and parenchymal asbestos-induced radiologic abnormalities and an association of nonanginal pain with parenchymal disease. We conclude that radiographic evidence of either parenchymal or pleural disease in subjects exposed to asbestos is significantly related to the presence of chest pain, particularly anginal pain.

ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models.

The recent development of genetic mouse models presenting life-long alterations in expression of the genes for atrial natriuretic peptide (ANP) or its receptors (NPR-A, NPR-C) has uncovered a physiological role of this hormone in chronic blood pressure homeostasis. Transgenic mice overexpressing a transthyretin-ANP fusion gene are hypotensive relative to the nontransgenic littermates, whereas mice harboring functional disruptions of the ANP or NPR-A genes are hypertensive compared with their respective wild-type counterparts. The chronic hypotensive action of ANP is determined by vasodilation of the resistance vasculature, which is probably mediated by attenuation of vascular sympathetic tone at one or several prejunctional sites. Under conditions of normal dietary salt consumption, the hypotensive action of ANP is dissociated from the natriuretic activity of the hormone. However, during elevated dietary salt intake, ANP-mediated antagonism of the renin-angiotensin system is essential for maintenance of blood pressure constancy, inasmuch as the ANP gene "knockout" mice (ANP -/-) develop a salt-sensitive component of hypertension in association with failure to adequately downregulate plasma renin activity. These findings imply that genetic deficiencies in ANP or natriuretic receptor activity may be underlying causative factors in the etiology of salt-sensitive variants of hypertensive disease and other sodium-retaining disorders, such as congestive heart failure and cirrhosis.