Relationship between carnosinase gene CNDP1 leucine repeat polymorphism and the clinical outcome of Chinese PD patients.

BACKGROUND: pre-clinical studies showed that carnosine may have a beneficial cardiovascular effect. We studied the effect of tri-nucleotide repeat (CTGs) polymorphisms in exon 2 of the CNDP1 gene, which codes for carnosinase and is responsible for the degradation of carnosine, on the clinical outcome of Chinese peritoneal dialysis (PD) patients. METHODS: we studied 442 PD subjects. Genotyping was done by direct sequencing of genomic DNA. Patients were followed for 43.5 ± 16.2 months. RESULTS: the prevalence of 6-6, 5-6, 5-5 and 4-6 CTGs genotypes was 80.3%, 18.6%, 0.9% and 0.2%, respectively. A total of 270 patients (61.1%) developed the primary composite end point during follow-up. The 5-year event-free survival of the 6-6 CTGs and non 6-6 group was 37.1% and 21.3%, respectively (log rank test, p = 0.3). CONCLUSION: the CTGs polymorphism of the CNDP1 gene does not affect survival of Chinese PD subjects. The role of carnosine and CNDP1 gene polymorphism in the pathogenesis of cardiovascular disease requires further study.

Relation between polymorphisms of receptor for advanced glycation end products (RAGE) and cardiovascular diseases in Chinese patients with diabetic nephropathy.

BACKGROUND: Interaction of receptor for advanced glycation end products (RAGE) with advanced glycation end products (AGEs) is an important pathogenic mechanism of diabetic complications. Three mutations in the promoter region of the RAGE gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides) were known to have increased transcriptional activities. We investigated the relationship between these polymorphisms and the risk of cardiovascular diseases in Chinese subjects with overt diabetic nephropathy. METHODS: A total of 219 Type 2 diabetic subjects with nephropathy were recruited. Genotyping of the three polymorphisms in the genomic DNA was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8 years for the development of cardiovascular events and survival. RESULTS: The T-429 C and T-374 A polymorphism had no effect on the event-free survival of the subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0% and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank test, p = 0.034). After adjusting for confounders, the 63 bp deletion polymorphism had a marginal effect on event-free survival (adjusted hazard ratio: 3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the three polymorphisms have significantly higher risk of first ischemic heart disease than those with any of the three mutations (adjusted hazard ratio: 0.218, 95% CI: 0.062 - 0.764, p = 0.017). CONCLUSION: The 63 bp del-/+ genotype of the RAGE gene has a marginal benefit on the cardiovascular event-free survival in subjects with diabetic nephropathy. Subjects with any of the three mutations have a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of cardiovascular disease in diabetic patients requires further study.

Intramedullary spinal cord metastases from small cell carcinoma of the lung.

Four patients with intramedullary spinal cord metastases from small cell carcinoma of the lung (SCCL) are described, with emphasis on clinical presentation and treatment. All patients developed the Brown-Séquard syndrome due to intramedullary tumor in the cervical spinal cord, three within 2 mo after combined modality treatment using chemotherapy and radiotherapy. One patient presented with a Brown-Séquard syndrome and an extradural spinal cord compression from tumor. The radiological and cerebrospinal fluid findings are presented and discussed. Radiation treatment was administered to the involved segments of spinal cord in each patient. All patients responded; two for 3 and 7 mo, two for 3 and 4 wk, respectively. There was significant improvement in the quality of life for three of the four patients.

Chromosomal telomere shortening of kidney cells in IgA nephropathy by the measurement of DNA in urinary sediment.

BACKGROUND: The histology and function of the kidney deteriorates with age and progressive renal failure, but the mechanisms involved in renal ageing are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stress factors that increase replication. We investigated whether IgA nephropathy, a prototype chronic kidney disease, is associated with localized intrarenal cellular ageing. METHODS: We studied the mean length of terminal restriction fragments (TRF), a measure of average telomere size, in the DNA of peripheral blood mononuclear cells and urinary sediment of 15 patients with IgA nephropathy. RESULTS: The mean TRF lengths in peripheral blood is 7043.8 +/- 1 182.8 base pairs, and in urinary sediment is 6 749.7 +/- 636.5 base pairs. The mean TRF lengths of urinary DNA significantly correlate with the serum creatinine (r = -0.525, p = 0.044) and estimated glomerular filtration rate (GFR) (r = 0.651, p = 0.009). The mean TRF lengths of urinary DNA had an insignificant inverse correlation with patient age (r = -0.364, p = 0.2), and do not correlate with the degree of glomerulosclerosis (r = 0.004, p = 0.9) or tubulointerstitial scarring in renal biopsy (r =-0.032, p = 0.9). After 30 months of follow-up, the rate of decline of estimated GFR has an inverse correlation with the mean TRF lengths of urinary DNA (r = -0.699, p = 0.004). The TRF lengths of peripheral blood DNA do not correlate with any clinical or histological parameter or the rate of renal function decline. CONCLUSIONS: Although this is a pilot study, our observation indicates that the TRF lengths of genomic DNA extracted from urinary sediment is related to the degree of renal impairment. However, a long telomere length of genomic DNA in urinary sediment is associated with a more rapid decline of renal function. Our findings might be relevant to the pathogenesis of progressive renal failure.

Acute radiation-induced pulmonary damage: a clinical study on the response to fractionated radiation therapy.

Acute radiation-induced pulmonary damage can be a significant cause of morbidity in radiation therapy of the thorax. A prospective, clinical study was conducted to obtain dose-response data on acute pulmonary damage caused by fractionated radiation therapy. The endpoint was a visible increase in lung density within the irradiated volume on a computed tomographic (CT) examination as observed independently by three diagnostic radiologists. Fifty-four patients with various malignancies of the thorax completed the study. CT chest scans were taken before and at preselected times following radiotherapy. To represent different fractionation schedules of equivalent biological effect, the estimated single dose (ED) model, ED = D X N-0.377 X T-0.058 was used in which D was the average lung dose within the high dose region in cGy, N was the number of fractions, and T was the overall treatment time in days. Patients were grouped according to ED and the percent incidence of pulmonary damage for each group was determined. Total average lung doses ranged from 29.8 Gy to 53.6 Gy given in 10 to 30 fractions over a range of 12 to 60 days. Five patient groups with incidence ranging from 30% (ED of 930) to 90% (ED of 1150) were obtained. The resulting dose-response curve predicted a 50% incidence level at an ED value (ED50) of 1000 +/- 40 ED units. This value represents fractionation schedules equivalent to a total average lung dose of 32.9 Gy given in 15 fractions over 19 days. Over the linear portion of the dose-response curve, a 5% increase in ED (or total dose if N and T remain constant), predicts a 12% increase in the incidence of acute radiation-induced pulmonary damage.

Quantitative effect of combined chemotherapy and fractionated radiotherapy on the incidence of radiation-induced lung damage: a prospective clinical study.

PURPOSE: The objective of this work was to assess the incidence of radiological changes compatible with radiation-induced lung damage as determined by computed tomography (CT), and subsequently calculate the dose effect factors (DEF) for specified chemotherapeutic regimens. METHODS AND MATERIALS: A prospective, clinical study was conducted to determine the response of normal lung tissue to combined chemotherapy and radiotherapy. Radiation treatments were administered once daily, 5 days-per-week. Six clinical protocols were evaluated: ABVD (adriamycin, bleomycin, vincristine, and DTIC) followed by 35 Gy in 20 fractions; MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) followed by 35 Gy in 20; MOPP/ABVD followed by 35 Gy in 20; CAV (cyclophosphamide, adriamycin, and vincristine) followed by 25 Gy in 10; and 5-FU (5-fluorouracil) concurrent with either 50-52 Gy in 20-21 or 30-36 Gy in 10-15 fractions. CT examinations were taken before and at predetermined intervals following radiotherapy. CT evidence for the development of radiation-induced damage was defined as an increase in lung density within the irradiated volume. The radiation dose to lung was calculated using a CT-based algorithm to account for tissue inhomogeneities. Different fractionation schedules were converted using two isoeffect models, the estimated single dose (ED) and the normalized total dose (NTD). RESULTS: A total of 102 patients were entered and 70 completed the study. Forty-two patients developed CT changes compatible with lung damage. The actuarial incidence of radiological pneumonitis was 71% for the ABVD, 49% for MOPP, 52% for MOPP/ABVD, 67% for CAV, 73% for 5-FU radical, and 58% for 5-FU palliative protocols. Depending on the isoeffect model selected and the method of analysis, the DEF was 1.11-1.14 for the ABVD, 0.96-0.97 for the MOPP, 0.96-1.02 for the MOPP/ABVD, 1.03-1.10 for the CAV, 0.74-0.79 for the 5-FU radical, and 0.94 for the 5-FU palliative protocols. CONCLUSION: Quantitative dose effect factors (DEF) were measured by comparing the incidences of CT-observed lung damage in patients receiving chemotherapy and radiotherapy to those receiving radiotherapy alone. The addition of ABVD or CAV appeared to reduce the tolerance of lung to radiation.

Magnetic resonance imaging for monitoring relapse of acute myeloid leukemia.

Magnetic resonance provides a non-invasive tool for monitoring normal and leukemic bone marrow. Measurements of the T1 relaxation times are elevated in acute myelogenous leukemia. However, interpatient variability diminishes the usefulness of MR measurements for diagnosing leukemia. In following the time course of individual patients, T1 relaxation time measurements appear to give an early and sensitive indication of leukemic relapse after remission and this may serve a clinical role in the management of leukemia by reducing the regularity of necessary marrow aspirates and biopsies.

A prospective evaluation of magnetic resonance imaging, computed tomography, and mediastinoscopy in the preoperative assessment of mediastinal node status in bronchogenic carcinoma.

Computed tomography, magnetic resonance imaging, chest roentgenography, and mediastinoscopy were compared prospectively as staging modalities to assess mediastinal node status in 84 patients with presumed operable bronchogenic carcinoma. Computed tomography was associated with a sensitivity of 71.0%, a specificity of 87.7% and an overall accuracy of 82.1%. Magnetic resonance imaging did not provide any advantage over computed tomography in the assessment of mediastinal node status. The accuracy of computed tomography was not dependent on cell type of the primary tumor. Although chest roentgenography had a sensitivity of 80.7%, the overall accuracy of 57.1% was unacceptably low. The sensitivity (87.1%), specificity (100%), positive (100%) and negative (93.0%) predictive values, and accuracy (95.2%) of mediastinoscopy exceeded those observed with all other modalities. We continue to recommend mediastinoscopy as the most accurate staging investigation in the routine management of patients with bronchogenic carcinoma.

Sensitivity and specificity of MRI in detecting malignant spinal cord compression and in distinguishing malignant from benign compression fractures of vertebrae.

The accuracy of magnetic resonance (MR) imaging in the detection of metastatic compression of the spinal cord and the cauda equina (MCCE) in 75 patients with known primary malignancy outside the central nervous system is determined retrospectively by comparing the MR results with findings of myelography, surgery, clinical follow-up and autopsy. The sensitivity is 93%, the specificity 97% and the overall accuracy 95%. The signal intensity measured in the sagittal MR images of a collapsed vertebral body is divided by that of an average of three adjacent normal vertebrae to form a signal intensity ratio (SIR). The SIRs of 41 metastatic and 15 post-traumatic collapsed vertebrae are calculated. A ratio of 0.8 has the most differentiating power. All benign and one malignant compressed vertebrae have SIRs greater than 0.8.

Nuclear magnetic resonance study of iron overload in liver tissue.

Whole-tissue and homogenized samples of human liver were studied in a NMR spectrometer, T1 and T2 relaxation times were measured as a function of added inorganic or organic iron. When inorganic iron (Fe+3) was added, pronounced T1 and T2 shortening was noted. However, when organic iron, in the form of ferritin, was added, the amount of T1 and T2 relaxation enhancement was much reduced for the same amount of added iron. The in vitro ferritin results model the situation found in clinical studies of hemochromatosis. Only in cases of severe iron overload were significant decreases in relaxation times observed. The T2 relaxation time was the more reliable indicator of excessive levels of iron in the liver. The large range of T1 and T2 values encountered in normal volunteers precludes the use of MR to quantitatively measure iron levels in the liver. The T1 and T2 relaxation times measured at intervals for one individual tend to fluctuate as well, making the use of MR to follow the course of treatment of iron overload disorders unreliable.

Computed tomography in staging primary uterine cervical carcinoma.

Pelvic computed tomography (CT) was done in 100 unselected patients with untreated carcinoma of the uterine cervix. The size of the primary tumor, its extension into vagina, parametria, utero-sacral ligaments, pelvic sidewalls, bladder and rectum and pelvic lymphadenopathy were determined. Independently, similar findings from pelvic examination under general anesthesia (EUA) and cystoscopy were also recorded. International Federation of Gynecology and Obstetrics (FIGO) staging was used for comparison. The staging according to CT in 69 patients (69%) agreed with that at EUA and cystoscopy. In 31 patients there was both understanding (15%) and overstaging (16%) by CT.

Gastroepiploic veins: CT appearance in pancreatic disease.

The frequency with which gastroepiploic vein (GEV) enlargement was seen on CT and its relevance to disease of the portal venous system associated with pancreatic disease were studied. We performed a retrospective study of 50 patients with proved pancreatic disease and another 50 patients without such disease. The CT examinations were done in incremental dynamic fashion after a bolus injection of contrast medium. Scans were evaluated for collateral channel formation, including GEV enlargement, and for involvement of the portal venous system by pancreatic disease. Part of the GEV arcade was visible in 36 patients without pancreatic disease, and on average measured 3.2 mm in diameter (range, 1-5.5 mm). GEV enlargement was visible in 62% of the patients with disease; 16% demonstrated a vessel 6 mm or more in diameter. Thirty-four percent of the patients with disease had portal venous complications: 26% had isolated splenic vein involvement, 2% had isolated portal vein involvement, and 6% had a combination of splenic and portal vein involvement. Of the patients with splenic vein disease, 81% had collateral channel formation, 50% of them demonstrating isolated GEV enlargement. Patients with splenic vein disease due to acute pancreatic disease had a much higher instance of GEV enlargement (83.3%). Collateral vessels are commonly seen on CT scans of patients with splenic vein disease and most often occur via enlarged GEVs. Acute pancreatic disease is frequently associated with GEV enlargement, suggesting that the latter represents an early response to splenic vein disease. In contrast, multiple collateral pathways tend to develop in patients with chronic pancreatic disease.

Radiologic studies of larynx after radiotherapy for carcinoma.

Antero-posterior linear tomography was used in conjunction with a xeroradiographic lateral view of the neck to study 35 cases of carcinoma of larynx previously treated by irradiation. Although false negatives and false positives did occur, this method is reasonably reliable in the diagnosis or exclusion of recurrent malignancy.

Patterns of breast parenchyma on mammography.

The hypothesis that two of four mammographic patterns show a marked predisposition to develop breast cancer was examined in a retrospective study. Four hundred patients with breast carcinoma were randomly chosen. The xeromammograms of the opposite breasts in these patients had been done and were studied. The conclusion of Wolfe was not supported by our findings.

Value of CT in diagnosing nonneoplastic osteolysis in Paget disease.

We present an unusual case of osteolysis, likely due to a stress fracture, in a pagetic pubic bone simulating sarcomatous transformation.

Magnetic resonance imaging of intracranial epidermoids: report of two cases.

Intracranial epidermoids are uncommon benign tumors in the subarachnoid spaces. We have studied two patients with these tumors originating in the basal cisterns using magnetic resonance (MR) imaging, computed tomography (CT), and cerebral angiography. Both CT and MR showed the extraaxial position of these tumors and their extension into the posterior fossa well. Angiography did not show any abnormal vasculature but displacement of vessels by the tumor mass was well demonstrated. MR was found to be relatively specific in characterizing these tumors.

Increased sialylation of polymeric immunoglobulin A1: mechanism of selective glomerular deposition in immunoglobulin A nephropathy?

Immunoglobulin A nephropathy (IgAN) is characterized by raised serum IgA and predominant mesangial IgA deposits of polymeric nature. The abnormal glycosylation of the carbohydrate moieties in the hinge region of the IgA molecule has recently attracted much attention. In this study we investigated the galactosylation and sialylation of monomeric and polymeric IgA1 isolated from patients with IgAN. Total IgA1 in serum samples from patients with IgAN or from healthy controls was isolated with a jacalin-agarose column as jacalin-bound protein (JBP). Monomeric and polymeric IgA1 were distinctly separated by fast protein liquid chromatography. Lectin binding assays were designed to examine the sialylation and the expression of terminal galactose and N-acetyl galactosamine of the O-linked carbohydrate in the hinge region of the IgA molecule. Reduced terminal galactosylation was demonstrated in serum IgA and monomeric IgA1 isolated from patients with IgAN as compared with results in healthy control subjects. However, a reduction in terminal galactosylation was not found in polymeric IgA1 isolated from patients with IgAN. Instead, increased sialylation of IgA1 (alpha2-3 linked to galactose) was demonstrated in polymeric IgA1. This abnormality of IgA1 could bear considerable implication on the pathogenesis of IgAN, because the masking effect of sialic acid may hinder the clearance of polymeric IgA1 by the asialoglycoprotein receptor (ASGP-R) of the liver cells. An increase in the sialylated content would also render the polymeric IgA from patients with IgAN more anionic. These immunochemical properties may contribute to the selective glomerular deposition of polymeric IgA1 in IgAN.

Psoas muscle calcification and acute renal failure associated with nontraumatic rhabdomyolysis: CT features.

We present a case of reversible psoas muscle calcification associated with acute renal failure and alcohol intoxication. The CT demonstration of calcification led to the recognition of rhabdomyolysis.

Tumour extent and T stage of nasopharyngeal carcinoma: a comparison of magnetic resonance imaging and computed tomographic findings.

PURPOSE: To compare magnetic resonance imaging (MRI) and computed tomography (CT) in defining the T stage and full tumour extent of nasopharyngeal carcinoma. PATIENTS AND METHODS: Forty-eight patients with pathologically proven nasopharyngeal carcinoma underwent MRI and CT examinations within 2 weeks of each other. Contrast medium was used in both examinations. The T stage and full tumour extent according to MRI and CT were compared. RESULTS: In 32 patients MRI and CT findings agreed completely. MRI findings resulted in assignment of a higher stage than CT findings in another 8 patients. In the remaining 8 patients MRI showed wider tumour spread than CT, although there was no discordance in the T stage assigned. CONCLUSION: When compared with CT in defining the full tumour extent and assigning the T stage in 48 patients with nasopharyngeal carcinoma, MRI showed more extensive disease in 16 patients, including 8 in whom the T stage was revised upward. Therapy was altered as a result of the MRI findings.