PubMed Health⌕ Search

Biomedical subjects

A Darnell

Publications and source records attributed to A Darnell.

At least 19 recordsLinked to original sources
PubMed2006

Gastrointestinal stromal tumors.

BACKGROUND: We reviewed radiologic features of gastrointestinal stromal tumors (GISTs) and correlated them with clinical and pathologic findings. METHODS: We investigated a series of 39 c-Kit-positive GISTs. Clinical and radiologic findings and management of these patients were recorded. RESULTS: Twenty women and 19 men (mean age 64 years) had histologically proved GIST. Tumor locations were the small bowel (n = 20), stomach (n = 14), rectum (n = 4), and omentum (n = l). Symptoms at presentation were most frequently gastrointestinal bleeding (n = 14) and abdominal pain (n = l1). Tumors were classified as very low risk (n = 2), low risk (n = 10), intermediate risk (n = 12), and high risk (n = 11). Ultrasonography, computed tomography, magnetic resonance, digital subtraction angiography, and barium series were used in the evaluation of these tumors. Most tumors were seen as well-delineated soft tissue masses with heterogeneous contrast enhancement. Necrosis, calcification, and ulceration were most commonly seen in large tumors that presented a more aggressive behavior. CONCLUSION: GISTs can arise anywhere in the gastrointestinal tract and present a great variety of clinical and radiologic features, depending mostly on size and location.

Adult↗
PubMed2004

The kidney in paroxysmal nocturnal haemoglobinuria: MRI findings.

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, acquired stem-cell disorder characterized by defective haematopoiesis, which results in an increased sensitivity of the erythrocytes to complement-mediated intravascular haemolysis. Renal damage is infrequent but can produce chronic renal failure due cortical deposits of haemosiderin and microvascular thrombosis. MRI provides characteristic images of the kidneys that enable haemosiderin deposition to be diagnosed; in PNH, MRI typically shows reversed renal cortex-medulla differentiation on T(1) weighted images and substantial loss of cortical signal intensity on both T(1) and T(2) weighted images. We describe the MRI findings of renal cortical haemosiderosis occurring in four patients with PNH.

Adult↗
PubMed2001

Circulating soluble adhesion molecules in ANCA-associated vasculitis.

BACKGROUND: To evaluate whether changes in concentrations of soluble (s) E-selectin, sP-selectin, sL-selectin, intercellular adhesion molecule 1 (sICAM-1), and vascular cell adhesion molecule 1 (sVCAM-1) reflect disease activity in patients with ANCA-associated vasculitis and whether serum levels of these adhesion molecules are related to the degree of renal failure in patients with chronic renal failure (CRF). SUBJECTS AND METHODS: A sandwich ELISA was used to measure these soluble adhesion molecules in (i) sera from 20 patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (10 patients with Wegener's granulomatosis (WG) and 10 patients with microscopic polyangiitis (MPA)), obtained at the time of diagnosis and during the remission period; (ii) sera from 40 patients with CRF not undergoing haemodialysis. RESULTS: At the time of diagnosis, serum levels of sE-selectin, sICAM-1 and sVCAM-1 (88+/-42 ng/ml, 437+/-184 ng/ml, 1720+/-1174 ng/ml respectively) were significantly higher in patients with ANCA-associated vasculitis than in healthy controls (P<0.0001, P=0.002 and P=0.001 respectively). Serum sP-selectin values did not differ from those obtained in normal donors. In contrast, sL-selectin levels (940+/-349 ng/ml) were significantly lower in patients than those recorded in healthy controls (P<0.0001). A significant decrease in concentrations of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 was observed between active and remission phases (P<0.0001, P=0.002, P=0.001 and P=0.001 respectively). No significant differences were observed in sL-selectin levels between active and remission phases. sL-selectin concentrations (802+/-306 ng/ml) during the remission phase remained lower than those observed in healthy controls (P<0.0001). No correlation was observed between serum creatinine and sE-selectin, sP-selectin, sICAM-1 and sVCAM-1 in patients of the CRF group. A slight negative correlation was established between creatinine and sL-selectin concentration. CONCLUSIONS: Increased serum levels of sE-selectin, sICAM-1, and sVCAM-1 and decreased levels of sL-selectin in active ANCA-associated vasculitis, and the normalization of sE-selectin, sICAM-1, and sVCAM-1 during the remission phase suggest that the concentration of soluble levels of these adhesion molecules reflects disease activity. The decrease in sP-selectin levels between active and inactive phases also suggest that this receptor may reflect clinical activity. The lack of correlation between serum levels of sE-selectin, sP-selectin, sICAM-1, and sVCAM-1 and the degree of renal failure in patients with CRF suggests that the mechanism of clearance of these molecules is not renal.

Adult↗
PubMed2001

Cardiovascular risk factors and the long-term outcome of lupus nephritis.

We evaluated cardiovascular risk factors, morbidity and mortality in patients with lupus nephritis (LN). We prospectively studied 70 consecutive patients with LN, and 70 age- and sex-matched controls with systemic lupus erythematosus (SLE) but no evidence of nephropathy, from 1988 to 1998. Patients were evaluated at entry for hypertension, diabetes, hyperlipidaemia, smoking, menopause and antiphospholipid syndrome. The LN patients (64 women, 6 men) had a mean age of 35 years (SE 1.7, range 11-67). During the 10 years, 15 (21%) LN patients and 18 (25%) of the controls were lost to follow-up. Compared with controls, LN patients had a higher prevalence of hyperlipidaemia (44% vs. 2%, p<0.001), hypertension (44% vs. 9%, p<0.001) and antiphospholipid antibodies (45% vs. 22%, p=0.01) at study onset. At the last visit, 37 (67%) LN patients had normal plasma creatinine, 13 (24%) had renal failure and only five (9%) end-stage renal failure. Hyperlipidaemia (78% vs. 27%, p<0.001) and hypertension (67% vs. 32%, p=0.01) at study onset were associated with development of renal failure. Nine LN patients and one control died (16% vs. 2%, p=0.02). These patients showed more antiphospholipid syndrome (56% vs. 17%, p=0.03) and hyperlipidaemia (78% vs. 37%, p=0.03) at study onset. The main causes of death in LN patients were vascular complications (cardiovascular or cerebrovascular events) in five patients (four of whom had antiphospholipid antibodies) and sepsis in three.

Adolescent↗
PubMed2001

Comparison of anti-PR3 capture and anti-PR3 direct ELISA for detection of antineutrophil cytoplasmic antibodies (ANCA) in long-term clinical follow-up of PR3-ANCA-associated vasculitis patients.

A total of 118 sera from 11 patients with anti-neutrophil cytoplasmic antibodies against proteinase-3- (PR3-ANCA) associated vasculitis were retrospectively screened by anti-PR3 capture and anti-PR3 direct ELISA tests. We studied the relationship between capture and direct ELISA scores and the clinical activity of PR3-ANCA-associated vasculitis patients during follow-up. We also studied the ability of the anti-PR3 capture ELISA to detect positive values of PR3-ANCA in clinical vasculitis relapses. Only capture ELISA presented a significant relationship (p < 0.05) with clinical activity of PR3-ANCA-associated vasculitis patients over time. Capture ELISA appears to be a reliable method for detecting clinical relapses in this group of patients. Our results indicate that the new capture ELISA test is more effective than direct ELISA in the follow-up of patients with PR3-ANCA-associated vasculitis and in the detection of relapses.

Adult↗
PubMed2000

Loss of heterozygosity in renal and hepatic epithelial cystic cells from ADPKD1 patients.

Autosomal dominant polycystic kidney disease (ADPKD) is one of the commonest genetic diseases in man, affecting 1:1000 individuals in the Caucasian population. It is caused by mutations in the PKD1 or PKD2 genes. Recently, controversial data regarding the mutational mechanism underlying cyst initiation have been reported: genetic analyses have shown that second somatic mutations may lead to cyst formation (detected as microsatellite loss of heterozygosity, LOH, and point mutations), but immunohistochemical studies show strong immunoreactivity for polycystin in some cysts. In order to further characterise this matter we have analysed 211 cysts from seven different patients for LOH, we have detected a 13.3% LOH for PKD1. This loss was specific to PKD1 as no LOH was detected when other chromosomal regions were studied. Whenever linkage analysis has been possible, it has been proved that the lost allele corresponded to the wild-type. Our data supports previous results in the two-hit theory for ADPKD due to the large number of cysts studied. ADPKD would occur through a recessive cellular mechanism. The probability of cyst development would depend on the probability of mutation in the second allele. The different phenotypical expression of the same mutation reported in ADPKD could be due to the different tendency of inactivation in the second allele in each individual.

Cells, Cultured↗
PubMed2000

Increased prevalence of polycystic kidney disease type 2 among elderly polycystic patients.

Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci (PKD1, PKD2, and PKD3) accounting for the disease. Mutations in the PKD2 gene, on the long arm of chromosome 4, are estimated to be responsible for 15% of the cases of ADPKD, based on linkage studies. PKD2 is a milder form of the disease, with a mean age of end-stage renal disease (ESRD) approximately 20 years later than PKD1. The object of this study is to determine the proportion of elderly patients with ADPKD with ESRD who harbor mutations in the PKD2 gene. We analyzed all exons and intron-exon boundaries of the PKD2 gene by single-strand conformation polymorphism analysis and silver staining technique in 46 patients with ADPKD who reached ESRD after the age of 63 years or were not yet undergoing renal replacement therapy (RRT) by that age. We performed exactly the same studies in a control group of 40 patients with ADPKD with unknown gene status aged younger than 63 years. In 22 patients, a mutation in the PKD2 gene was defined: 18 of 46 patients from the elderly group and 4 of 40 patients from the control group. We identified 14 different mutations: 4 nonsense mutations, 1 missense mutation, 5 small deletions, 2 insertions, 1 deletion of the whole PKD2 gene, and 1 splicing mutation. Five of these mutations previously were described by our group. Three of the mutations reported in the present study are recurrent. The prevalence of PKD2 disease among elderly patients with ADPKD undergoing RRT is 39.1%, almost three times the prevalence of the disease in the general ADPKD population.

Adult↗
PubMed2000

Serum cystatin C as a new marker for noninvasive estimation of glomerular filtration rate and as a marker for early renal impairment.

Cystatin C is a nonglycosylated basic protein produced at a constant rate by all investigated nucleated cells. It is freely filtered by the renal glomeruli and primarily catabolized in the tubuli (not secreted or reabsorbed as an intact molecule). Because serum cystatin C concentration is independent of age, sex, and muscle mass, it has been postulated to be an improved marker of glomerular filtration rate (GFR) compared with serum creatinine level. We compared serum cystatin C level with other markers of GFR, such as serum creatinine level and creatinine clearance, and analyzed their variations based on iothalamate labeled with iodine 125 ((125)I-iothalamate) clearance ((125)I-ICl), used as the gold standard for GFR. The concentrations of the two different markers of GFR in patients with impaired renal function were classified according to (125)I-ICl. Twenty individuals with normal renal function ((125)I-ICl, 128 +/- 23 mL/min/1.73 m(2)) were used as the control group. Serum cystatin C level showed a greater sensitivity (93.4%) than serum creatinine level (86.8%). Also, serum cystatin C showed the greatest proportion of increased values in patients with impaired renal function (100%) compared with serum creatinine level (92.15%). Serum cystatin C levels started to increase to greater than normal values when GFR was 88 mL/min/1.73 m(2), whereas serum creatinine level began to increase when GFR was 75 mL/min/1.73 m(2). These data suggest that measurement of serum cystatin C may be useful to estimate GFR, especially to detect mild reductions in GFR, and therefore may be important in the detection of early renal insufficiency in a variety of renal diseases for which early treatment is critical.

Biomarkers↗
PubMed2000

Sonographic pattern of recessive polycystic kidney disease in young adults. Differences from the dominant form.

BACKGROUND: To study the sonographic pattern of autosomal recessive polycystic kidney disease (ARPKD) in early adulthood in order to identify imaging criteria to diagnose this disease and to distinguish between recessive and autosomal dominant polycystic kidney disease (ADPKD) in that age group. METHODS: An abdominal ultrasound was performed on four ARPKD subjects (with a mean age of 20.2) and on 33 ADPKD subjects in early adulthood (29 without renal failure with a mean age of 20.5, and four with renal failure with a mean age of 26.5). Linkage studies with ADPKD and ARPKD markers were compatible with the clinical diagnosis in all cases. RESULTS: The renal sonographic features in ARPKD subjects included multiple small cysts in a normal-sized kidney, increased cortical echogenicity and loss of corticomedullary differentiation. In ADPKD subjects without renal failure, sonographic features included few or multiple cysts of different sizes, in normal-sized kidneys in 22 out of 29 patients (75.8%), normal cortical echogenicity and conserved corticomedullary differentiation, except in patients with nephromegaly. All ADPKD subjects with renal failure had nephromegaly and loss of corticomedullary differentiation. The hepatic sonographic features in ARPKD patients included portal fibrosis and in some cases Caroli's disease, while in ADPKD patients a normal hepatic echostructure was detected in all but one case, in addition to simple hepatic cysts in a few cases. CONCLUSIONS: The evaluation of the sonographic features of the kidneys and those of the liver may help in the differential diagnosis between ARPKD and ADPKD in early adulthood.

Adult↗
PubMed1999

[Genetic polymorphisms of the renin-angiotensin system and essential hypertension].

BACKGROUND: The renin-angiotensin system (RAS) plays an important role in blood pressure (BP) regulation. A number of RAS polymorphisms have been linked to essential hypertension (EH), but there is uncertainty about this association in other studies. We examined whether the insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the M235T and T174M polymorphisms of the angiotensinogen (AGT) gene are associated with EH in a Spanish sample of hypertensive patients. MATERIAL AND METHODS: We studied 75 patients with EH (BP > 160/100 mmHg), aged 55 (8.5) years, 30 males, systolic BP (SBP) 182 +/- (22.1) mmHg, diastolic BP (DBP) 109 +/- (9.9) mmHg (mean [SD]) and a strong family history of the disease. As a control group, 75 healthy subjects with no family history of cardiovascular disease were studied. The polymorphisms were determined by PCR amplification of genomic DNA, followed by enzyme digestion for the AGT gene polymorphisms. RESULTS: The genotype distribution and the frequencies of the alleles of the three RAS polymorphisms were similar in hypertensive and control subjects. In addition, we did not find any compound effect of the I/D ACE gene and M235T AGT gene polymorphisms on BP levels in hypertensive and control subjects. CONCLUSIONS: In this sample, the contribution of the ACE I/D polymorphism and the AGT M235T and T174M polymorphisms in the development of EH seems to be less important than previously estimated.

Adult↗
PubMed1999

Effect of catecholamine depletion on lithium-induced long-term remission of bipolar disorder.

BACKGROUND: This study investigated the effects of catecholamine depletion with alpha-methylparatyrosine (AMPT) on mood indices in patients with bipolar disorder who were in long-term remission with lithium therapy. METHODS: Eight subjects with DSM-IV bipolar disorder currently in remission for > 3 months on lithium were included in the study. Subjects were given either AMPT or placebo, in a randomized double-blind manner, in two test sessions of 4 days each. RESULTS: Subjects did not have any significant changes in mood during AMPT or placebo administration; however, 24-48 hours after the last active AMPT dose subjects had a transient relapse of hypomanic symptoms. Relapse of hypomanic symptoms did not correlate with increases in serum levels of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol. CONCLUSIONS: These findings suggest that the mechanism of prevention of manic relapse by long-term lithium therapy may be dependent on stability of the catecholamine system.

Adult↗
PubMed1999

Influence of the ACE gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease.

The recent description of a polymorphism in the gene for angiotensin-converting enzyme (ACE), with the D allele associated with greater plasma levels of ACE, allows us to perform studies of the relationship between this polymorphism and chronic renal diseases in which the renin-angiotensin system could be implicated. We examined 155 patients with autosomal dominant polycystic kidney disease (ADPKD) with linkage to the PKD1 locus. The ACE insertion/deletion (I/D) polymorphism was amplified with the previously published flanking primers, and the polymerase chain reaction product was separated, sized on a 2% agarose gel, and visualized by ultraviolet transillumination. The ACE genotype distributions were 11.6%, 63.8%, and 24.5% for II, ID, and DD, respectively. There were no significant differences among the three genotypes with respect to mean age, sex distribution, and prevalence of hypertension. The ACE genotype distribution in patients with end-stage renal failure at the time of data compilation was similar to that of the entire study population. In the subgroup of patients who received renal replacement therapy before the age of 50 years, we found a significant association between DD genotype and onset of end-stage renal disease (ESRD) before the age of 50 years compared with II and ID (P = 0.017). We calculated the estimated median renal survival time as 51 years for the II genotype, 53 years for the ID genotype, and 48 years for the DD genotype. There were statistically significant differences between DD and ID patients (P = 0.025). In conclusion, we found DD genotype implies a worse renal prognosis based on both the significantly lower median renal survival time and significantly greater percentage of patients who reach ESRD before the age of 50 years, without implying a greater prevalence of hypertension.

Adult↗
PubMed1999

Primary lymphoma of the breast: MR imaging features. A case report.

Primary non-Hodgkin's lymphoma (NHL) of the breast are rare and represent less than 0.6% of all mammary malignancies. Secondary involvement of the breast in patients with diffuse disease occurs more frequently. The radiologic features of breast lymphoma are nonspecific, and the diagnosis is based on histologic criteria. We present the MR-imaging features of a case of primary NHL of the breast.

Biopsy, Needle↗
PubMed1999

Mutational analysis within the 3' region of the PKD1 gene.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases in humans, affecting 1 out of 1000 individuals. At least three different genes are involved in this disease. The search for mutations in PKD1 is complicated because most of the transcript is encoded by a genomic region reiterated more proximally on chromosome 16, and no prevalent mutation has been reported. METHODS: We have screened DNA from exon 43 through exon 46 and intron 40 of the PKD1 sequence by single-stranded conformational polymorphism (SSCP) analysis in 175 ADPKD patients. RESULTS: We have found 25 differences with respect to the reported PKD1 DNA sequence, seven of which are mutations (Q4041X, Q4124X, IVS44-1G-->C, IVS45-1G-->A, 12801del28, R4275W, and Q4224P). We found different phenotypical expressions of the same mutation in the families studied. We have detected several common polymorphisms, and some of them cosegregate, suggesting a common origin of these alleles in PKD1. CONCLUSIONS: The detection of only seven mutations in 175 unrelated ADPKD patients for this region of the PKD1 analyzed suggests that mutations could be widespread throughout all of the gene and that a prevalent mutation is not expected to occur. The identified PKD1 missense mutations may help to refine critical regions of the protein. Until a quicker and more sensitive method for the detection of mutations becomes available, linkage studies will continue to be the basis for the molecular diagnosis of ADPKD families.

Adult↗
PubMed1999

Seven novel mutations of the PKD2 gene in families with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci accounting for the disease. Mutations in the PKD2 gene on the long arm of chromosome 4 are expected to be responsible for approximately 15% of cases of ADPKD. METHODS: We report a systematic screening for mutations covering the 15 exons of the PKD2 gene in eight unrelated families with ADPKD type 2, using the heteroduplex technique. RESULTS: Seven novel mutations were identified and characterized that, together with the previously described changes, amount to a detection rate of 85% in the population studied. The newly described mutations are two nonsense mutations, a 1 bp deletion, a 1 bp insertion, a mutation that involves both a substitution and a deletion (2511AG-->C), a complex mutation in exon 6 consisting of a simultaneous 7 bp inversion and a 4 bp deletion, and the last one is a G-->C transversion that may be a missense mutation. Most of these mutations are expected to lead to the formation of shorter truncated proteins lacking the carboxyl terminus of PKD2. We have also characterized a frequent polymorphism, Arg-Pro, at codon 28 in this gene. The clinical features of these PKD2 patients are similar to the previously described, with the mean age of end-stage renal disease being 75.5 years (SE +/- 3.8 years). CONCLUSIONS: Our results confirm that many different mutations are likely to be responsible for the disease and that most pathogenic defects probably are point or small changes in the coding region of the gene.

Amino Acid Sequence↗
PubMed1999

A loss-of-function model for cystogenesis in human autosomal dominant polycystic kidney disease type 2.

Autosomal dominant polycystic kidney disease (ADPKD) is genetically heterogeneous, with at least three chromosomal loci (PKD1, PKD2, and PKD3) that account for the disease. Mutations in the PKD2 gene, on the long arm of chromosome 4, are expected to be responsible for approximately 15% of cases of ADPKD. Although ADPKD is a systemic disease, it shows a focal expression, because <1% of nephrons become cystic. A feasible explanation for the focal nature of events in PKD1, proposed on the basis of the two-hit theory, suggests that cystogenesis results from the inactivation of the normal copy of the PKD1 gene by a second somatic mutation. The aim of this study is to demonstrate that somatic mutations are present in renal cysts from a PKD2 kidney. We have studied 30 renal cysts from a patient with PKD2 in which the germline mutation was shown to be a deletion that encompassed most of the disease gene. Loss-of-heterozygosity (LOH) studies showed loss of the wild-type allele in 10% of cysts. Screening of six exons of the gene by SSCP detected eight different somatic mutations, all of them expected to produce truncated proteins. Overall, >/=37% of the cysts studied presented somatic mutations. No LOH for the PKD1 gene or locus D3S1478 were observed in those cysts, which demonstrates that somatic alterations are specific. We have identified second-hit mutations in human PKD2 cysts, which suggests that this mechanism could be a crucial event in the development of cystogenesis in human ADPKD-type 2.

Aged↗