Magnetic resonance imaging in the diagnosis and follow up of Takayasu's arteritis in children.

BACKGROUND: Takayasu's arteritis (TA) has a mortality rate of up to 40% in children. Because the clinical presentation of TA is often non-specific, accurate and prompt diagnosis depends on a high degree of awareness and appropriate laboratory and imaging studies. OBJECTIVE: To examine the use of advanced magnetic resonance imaging (MRI) in evaluating, gauging activity, and following the complications of TA. METHODS AND RESULTS: T1 weighted, T2 weighted, contrast enhanced MR images, and MR angiograms of the chest and abdomen were obtained in three children (age range 11-14 years). The MRI studies confirmed the diagnosis of active TA and were repeated to evaluate response to treatment. Two patients showed complete resolution of lesions found on MRI at six and 12 months' follow up, while the third patient showed no significant improvement. CONCLUSION: MRI can be used to help establish the initial diagnosis of TA in children, and it can also be used to monitor disease activity and to guide treatment.

Cigarette smoking and rheumatoid arthritis.

OBJECTIVES: To examine and explore the potential relationships among the following: the incidence/severity of rheumatoid arthritis (RA), the extra-articular manifestations of RA, vascular disease, certain specific malignancies, the p53 tumor suppressor gene, and cigarette smoking. METHODS: The medical literature was reviewed from 1985 to 2001 with the assistance of a MEDLINE search using the key words vascular disease, smoking, protein p53, RA, rheumatoid vasculitis, cancer, and malignancies. A qualitative review was performed after all articles were abstracted and new information summarized. RESULTS: Cigarette smoking has been increasingly shown in epidemiologic and case-control studies to be an important risk factor for both the incidence and severity of RA, especially in seropositive men. Further, there is evidence of a downward trend in incidence of extra-articular manifestations of RA, especially RA vasculitis, observed with a decrease in worldwide tobacco use and overall improved mortality in RA. The association of cigarette smoking with lung and other cancers and its link to vascular disease (including Buerger's disease) and atherosclerosis appears secure. Mutations or alterations in p53, a suppressor gene that regulates cell growth, have been found in certain cancers, cigarette smokers, and in patients with RA. CONCLUSIONS: Cigarette smoking appears to have an undeniable link to the pathogenesis of vascular disease of many types, including the possibility of a strong causal connection to rheumatoid vasculitis. The observations worldwide of decreasing tobacco use along with secular trends of diminished RA vasculitis and extra-articular manifestations, and with improved survival, points to a better outcome for our patients. The example of p53 may be a first step in the discovery of additional links between environmental triggers and phenotypic expression of chronic illness.

Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8+CD28(lo) T cells in patients with systemic lupus erythematosus.

To evaluate whether the immune system of systemic lupus erythematosus (SLE) patients shows features of premature aging, we compared telomere length and proliferative potential of SLE peripheral blood mononuclear cells (PBMC) (N = 90) to those of controls (N = 64). SLE samples showed accelerated loss of telomeric DNA (P = 0.00008) and higher levels of senescent (< or =5 kb) telomeric DNA (P = 0.00003). Viability cell counts and CFSE tracking in 6-week-old cell cultures indicated that SLE PBMC (CD8+ and CD4+ T cells) underwent fewer mitotic cycles and had shorter telomeres than controls (P = 0.04). However, a CD8(+)CD28(lo) T cell subset expanded preferentially in SLE-derived bulk cultures (P = 0.0009), preserved telomeric DNA (P = 0.01 vs entire CD8+), and displayed telomerase activity [2.1 telomerase arbitrary units (TAU) vs 0.5 TAU in CD8+CD28(hi) cells and 0.3 TAU in bulk PBMC; P = 0.05]. These T cell anomalies could be due to chronic in vivo stimulation of the immune system and may contribute to the immune dysregulation found in SLE.

Intragraft expression of transforming growth factor-beta 1 by a novel quantitative reverse transcription polymerase chain reaction ELISA in long lasting kidney recipients.

BACKGROUND: Chronic allograft nephropathy (CAN) remains a major problem in clinical transplantation. It has been associated with increased transforming growth factor (TGF-beta1). Our goal was to correlate CAN and levels of TGF-beta1 by using a novel competitive quantitative for reverse transcription-polymerase chain reaction-ELISA (RT-PCR-ELISA) assay. METHODS: We studied 12 transplantation patients (posttransplant time: 36.5+/-11.2 months, range (r): 13-52) with stable creatinine and blood pressure and varied proteinuria. A Kidney biopsy was performed in all patients. Six patients with acute tubular necrosis (ATN) immediately after transplantation were used as controls. Histopathological evaluation was based on Banff working classification criteria. We designed an heterologous RNA competitor (IC) for RT-PCR-ELISA, which co-amplified with the same primer as TGF-beta1. Products were viewed on 96-well plates labeled with probes for IC at the desired sequence. RESULTS: Results were expressed as the number of TGF-beta1 copies/microg of total RNA. Six patients showed more than 1000 mg/24 hr proteinuria (2446+/-1421 mg/24 hr, r: 1200-5000) higher CAN Banff scores, and the other six presented <1,000 mg/24 hr (348+/-267 mg/24 hr, r: 114-800). This difference was significant (P=0.01). There were not significant differences in posttransplant time, creatinine, or blood pressure between groups. TGF-beta1 levels by RT-PCR-ELISA were statistically significant (6038+/-5317, r: 1239-12100 versus 177+/-119.7, r: 51-400, P=0.04). The control group showed levels of 228+/-111, r. 140-444, P=0.04) with significant difference only for the higher proteinuria group (P=0.03). CONCLUSIONS: This study showed that those patients with elevated CAN scores and higher proteinuria levels had higher TGF-beta1 intragraft expression.

VH4-34 encoded antibodies in systemic lupus erythematosus: a specific diagnostic marker that correlates with clinical disease characteristics.

OBJECTIVE: To determine the clinical significance of elevated serum levels of VH4-34 encoded antibodies (VH4-34 Ab) with respect to the diagnosis and clinical characteristics of systemic lupus erythematosus (SLE). METHODS: Ninety-five patients with SLE and 344 controls were studied. The controls included 34 healthy individuals, 282 patients with nonautoimmune diseases, and 28 patients with autoimmune diseases other than SLE. VH4-34 Ab levels were measured by inhibition ELISA using anti-idiotope monoclonal antibody (9G4). SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. RESULTS: Fifty-two of 95 patients with SLE had elevated levels of VH4-34 Ab compared to 18 of 344 controls (5%), giving a sensitivity of 55% and a specificity of 95% for elevated VH4-34 Ab as a serologic test for SLE. The positive predictive value of elevated VH4-34 under these conditions was 74-85%. In this study, anti-dsDNA was not VH4-34 encoded. Significant correlations between VH4-34 and disease activity and severity indices were observed (r = 0.29-0.50). The relative risk for severe disease in SLE patients with VH4-34 antibody level in the highest tertile compared to the lowest tertile was 5.25. Twenty-five of 29 patients with lupus nephritis and 6 of 6 patients with central nervous system (CNS) lupus had elevated VH4-34 Ab. CONCLUSION: With a specificity of 94-95%, the VH4-34 antibody assay may prove valuable as a confirmatory diagnostic test for SLE. In patients with known SLE, serum VH4-34 Ab levels correlate with overall disease severity and activity, but not damage, and with nephritis and CNS lupus.

Utility of cytomegalovirus viral load in renal transplant patients in Argentina.

BACKGROUND: Cytomegalovirus (CMV) is the most prevalent viral disease in solid organ transplantation. Detection of CMV DNA in peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR) frequently occurs in renal allograft recipients, yielding false positive results in seropositive patients free of CMV disease. We evaluated the clinical utility of a quantitative PCR-enzyme-linked immunosorbent assay (ELISA) for identifying patients with CMV disease. METHODS: Three hundred and fifty samples from 65 consecutive renal transplant recipients were studied. DNA was extracted from PBMC weekly up to the day of discharge and after any further admission. Samples were tested by a qualitative PCR method, and all positive samples were further studied by a quantitative PCR-ELISA method. The quantitative PCR-ELISA method used an internal standard (IS) that contained the primer sequences used in the qualitative CMV PCR. Detection and quantification was performed in 96-well plates coated with IS or CMV specific probes. RESULTS: Forty-one of 65 patients (63.1%) showed positive results by the qualitative PCR, but only 8 of these patients were diagnosed with CMV disease. Positive samples were re-analyzed by the quantitative assay. The 8 patients with CMV disease had a mean CMV viral load of 1,438+/-687 viral copies (VC)/10(6) PBMC, and the 33 without CMV disease had a mean value of 219.6+/-117.2 VC/10(6) PBMC (P<0.01). None of the 33 patients without CMV disease had viral loads higher than 500 VC/10(6) PBMC. Using 500 VC/10(6) PBMC as a cut-off value for CMV disease, the quantitative PCR showed a sensitivity and specificity of 100% compare to clinical diagnosis. CONCLUSION: CMV viral load may be useful in the diagnosis of CMV disease in renal transplant patients.

Rhabdomyolysis associated with naltrexone.

OBJECTIVE: To report a possible association between naltrexone therapy and the development of rhabdomyolysis in one patient. CASE SUMMARY: A 28-year-old white man in good physical health was started on naltrexone 50 mg/d for inpatient treatment of alcohol dependence and depression. A routine serum chemistry panel obtained on day 9 of naltrexone therapy showed marked new elevations in creatine kinase and aspartate aminotransferase. The patient remained asymptomatic and did not develop renal insufficiency. The serum enzyme concentrations returned to normal within eight days of naltrexone discontinuation. DISCUSSION: Rhabdomyolysis has not been previously reported to occur in patients during treatment with naltrexone. Alcoholism may result in a reversible acute muscle syndrome, but our patient did not fit the appropriate clinical profile for such a syndrome. Additionally, the other prescribed medications could not be implicated as possible causative agents. CONCLUSIONS: This case report illustrates a possible association between naltrexone therapy and rhabdomyolysis.

[Role of diagnostic imaging in Rubinstein-Taybi syndrome. Personal experience with 8 cases]. / Ruolo della diagnostica per immagini nella sindrome di Rubinstein-Taybi. Esperienza personale su 8 casi.

Both etiology and pathogenesis of Rubinstein-Taybi syndrome (RTS) are still questionable, even though a genetic factor seems to be certain. A typical face, psychomotor delay, and thumb and halluces abnormalities (big, prevalently short, and often "spoon-like" toes) are the main characteristic patterns of RTS. Eight subjects (4 male and 3 female children aged 26 days-7 years, and a 31-year-old woman, mother of 1 of the affected children) with different signs of RTS were studied over the last 3 years. The results are here reported, with a special emphasis on malformations detected with conventional radiography (Rx), Computerized Tomography (CT), and ultrasound (US). Evaluated parameters were thumbs and halluces (Rx), bone age and skeleton (Rx), cranium (Rx) and encephalon (US, CT), cryptorchidism (US, CT), and urological (Rx, US) and cardiovascular (US) systems. A typical face and psychomotor delay were found in all cases, while thumb and halluces abnormalities were observed only in 6 cases. Among several clinical signs of RTS, we found: severe (less than 3rd centile) bone maturation delay in 4 cases; skull volume reduction (less than 50th centile) in 3 subjects and microcrania in 4; skeletal abnormalities in 7 cases (5 of them positive for bilateral coxofemoral abnormalities); urinary tract (4 cases) and cardiovascular (3 cases) malformations; and cryptorchidism in 3 of 4 males. A case was diagnosed during neonatal period (within the first month of life); it was a rare case associated with a variant form of Dandy-Walker anomaly; semiologic similarities were observed between mother and daughter patients. X-rays, US and CT rarely play an important role in the diagnosis of RTS, considering the several clinical signs, mainly the face, affecting the patients. However, diagnostic imaging techniques help diagnose hidden malformations and confirm and integrate clinical signs.

Kabuki make-up (Niikawa-Kuroki) syndrome: clinical and radiological observations in two Sicilian children.

The Authors describe two patients aged 5 and 8, a female and a male, affected by a condition of polymalformations known as Kabuki make-up or Niikawa-Kuroki syndrome, having a neonatal incidence of 1:32,000 in Japan. There are two hypothesis about the apparent rarity of the syndrome in the rest of the world, including the Asian Continent: the first is that it exists, but is infrequently recognized outside Japan and the second is that it is really more frequent in those parts of the world, where ethnic exchanges are uncommon, as it happens in Japan.

[Ultrasonics in the diagnosis and monitoring of cryptorchism in children]. / L'ecotomografia nella diagnosi e nel monitoraggio del criptorchidismo infantile.

The diagnostic reliability of US was investigated in the study of cryptorchidism during a 9-month clinical and US trial performed on 52 children (mean age 4.3 years). Cryptorchidism was unilateral in 44 cases (24 on the left side and 20 on the right side), and bilateral in 8 cases. Of 60 cryptorchid testes, 53--belonging to 45 of 52 patients--were located in the inguinal region (18 along the canal, 20 at the external ring, and 15 at the internal one); the others 7--belonging to the remaining 7 subjects--were found in an extra-inguinal region (4 in paravesical location and 3 in the inferior abdomen). US confirmed 29 undescended testes with clinical evidence in the inguinal region and identified, in the same area, 24 other testes which had been missed at clinical examination. In addition, US provided useful information as to both structure and volumetry of the gonads. On the other hand, US failed to provide reliable diagnostic results in the rare cases of pelvic and abdominal cryptorchidism, where precise testes localization was achieved by CT. US is the diagnostic technique of choice in the study of cryptorchidism (after clinical examination): the method is non-invasive and simple, has low cost and its use is widespread; moreover, US does not administer ionizing radiations. According to our experience, US had 88.3% diagnostic sensitivity as for undescended testes (53 of 60), and 100% specificity. In addition, US monitoring allowed clinical efficacy of therapeutic trials to be verified in 25 patients (17 sensitive to therapy): 16 of them were treated with human Chorionic Gonadotropin (hCG) and 9 with Luteinizing Hormone-Releasing Hormone (LH-RH).

[Diagnostic problems in the echographic demonstration of appendiceal mucocele. Description of a case]. / Problemi diagnostici nell'accertamento ecografico del mucocele appendicolare. Descrizione di un caso.

The ultrasound diagnosis of appendicular mucocele may sometimes present problems in relation to its differentiation from other space-occupying intra or extra-peritoneal lesions. An observed case is described in which the echographic pattern of the mass suggested other diagnostic possibilities.

Inappropriate activation, deactivation, and probable autooxidative damage as a mechanism of neutrophil locomotory defect in trauma.

We studied 46 patients who suffered from serious blunt trauma to examine the possible mechanism of their acquired neutrophil (PMN) locomotory dysfunction. Concentrations of plasma C3adesArg were higher in patients than in controls (310 +/- 190 ng/ml vs. 90 +/- 28 ng/ml, respectively; P = 3 X 10(-5)). Both resting and phagocytosing PMNs from the patients produced higher quantities of H2O2 (0.31 +/- 0.29 and 5.2 +/- 3.4 nmol/10(6) PMNs per hr, respectively). These levels resemble the H2O2 production of normal PMNs preactivated with chemotactic factor (0.85 +/- 0.03 for normal and 8.2 +/- 1.6 nmol/10(6) PMNs per hr for preactivated PMNs). Concentrations of oxidized glutathione were not significantly higher in PMNs from patients compared with PMNs from controls (0.053 +/- 0.057 vs. 0.037 +/- 0.046 nmol/10(6) PMNs, respectively; P = .5). A higher percentage of PMNs from trauma patients than from controls were capped with concanavalin A (66% +/- 11% vs. 37% +/- 14%, respectively; P = 4 X 10(-5)), a result indicating microtubular dysfunction. These findings suggest that in trauma, activation of intravascular complement results in inappropriate chemotactic stimulation and subsequent deactivation and autoxidative damage of circulating PMNs.

Granulocyte migration abnormality in patients suffering from seasonal allergic rhinitis: failure of treatment with cimetidine.

Granulocyte locomotory responses in 5 patients with symptomatic seasonal allergic rhinitis were lower compared with similar responses from 27 normal nonallergic controls. In a subsequent controlled, double-blind crossover study, neither cimetidine (histamine H2-receptor blocker) nor placebo improved these responses. In our in vitro study, histamine did not inhibit granulocyte responses to chemotactic attractant. These results indicate that defective granulocyte response in patients with seasonal allergic rhinitis may be due to factors other than or in addition to histamine.

Polymorphonuclear leukocyte migration abnormalities and their significance in seriously traumatized patients.

Polymorphonuclear leukocyte (PMN) locomotory responses were studied in 24 patients who sustained serious blunt trauma, mostly from motor vehicle accidents. The results showed the presence of a combined cell- and serum-associated locomotory abnormality. The serum abnormality was due to a cell-directed inhibitor, and was present for an average of 3 days. The cell-associated abnormality persisted for approximately 1 week in uninfected patients, and 2 weeks in the infected group. Both mature and immature forms of PMNs contribute to the PMN locomotory dysfunction observed. A significant correlation was observed between the degree of PMN locomotory abnormality or injury severity score and the infection rate. Eighteen infections (six suspected and 12 definite) were observed in 11 of the 24 patients. Twelve (67%) infections involved the lungs. Nine patients (82%) showed evidence of infection by day 6. PMN dysfunction in trauma is associated with increased infection rate and is not due solely to increased numbers of immature forms of PMNs.

Regulation of antibody formation in chickens escaping from tolerance to human serum albumin.

The immune capacity of chickens made tolerant to human serum albumin just after hatching was studied after a primary and secondary challenge at 7--14 weeks of age, of either 1 mg/kg or 100 mg/kg. The class and avidity of antibody produced by birds "escaping" from tolerance was similar to normal controls. The escaping chickens made a normal peak antibody response to a high dose but not to a low dose (except that the response to a low secondary dose after priming with a high dose was normal); but the decline of the antibody titer was abrupt, indicating inability to maintain the response. It is concluded that the antibody-forming capacity of B cells is normal, but regulation of antibody formation is impaired in previously tolerant chickens.