Renal arteries: navigator-gated balanced fast field-echo projection MR angiography with aortic spin labeling: initial experience

A cardiac-triggered free-breathing three-dimensional balanced fast field-echo projection magnetic resonance (MR) angiographic sequence with a two-dimensional pencil-beam aortic labeling pulse was developed for the renal arteries. For data acquisition during free breathing in eight healthy adults and seven consecutive patients with renal artery disease, real-time navigator technology was implemented. This technique allows high-spatial-resolution and high-contrast renal MR angiography and visualization of renal artery stenosis without exogenous contrast agent or breath hold. Initial promising results warrant larger clinical studies.     

Clinical value of somatostatin receptor imaging in patients with suspected head and neck paragangliomas

Paragangliomas or glomus tumours of the head and neck region are rare somatostatin receptor-expressing neuroendocrine tumours. Precise preoperative diagnosis is of special importance in order to adequately weigh the potential benefit of the operation against the inherent risks of the procedure. In this study, the clinical value of somatostatin receptor imaging was assessed in 19 patients who underwent somatostatin receptor scintigraphy because of known or suspected paraganglioma of the head and neck region. The results were compared with the results of computed tomography and/or magnetic resonance imaging, histology and clinical follow-up. [(111)In-DTPA- D-Phe(1)]-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 140-220 MBq (111)In-octreotide. Whole-body and planar images as well as single-photon emission tomography images were acquired and lesions were graded according to qualitative tracer uptake. Somatostatin receptor imaging was positive in nine patients, identifying paragangliomas for the first time in three patients and recurrent disease in six patients. In one patient, a second, previously unknown paraganglioma site was identified. Negative results were obtained in ten patients. These patients included one suffering from chronic hyperplastic otitis externa, one with granuloma tissue and an organised haematoma, one with an acoustic neuroma, one with an asymmetric internal carotid artery, two with ectasia of the bulbus venae jugularis and one with a jugular vein thrombosis. In two patients with a strong family history of paraganglioma, individual involvement could be excluded. In only one patient did somatostatin receptor imaging and magnetic resonance imaging yield false negative results in respect of recurrent paraganglioma tissue. It is concluded that somatostatin receptor scintigraphy provides important information in patients with suspected paragangliomas of the head and neck region and has a strong impact on further therapeutic management.     

Repuncturing the renal biopsy: strategies for molecular diagnosis in nephrology

As has been exemplified by recent progress in the classification of cancer, future approaches to enhance the clinical diagnostic power of tissue biopsies may be based on gene expression profiles. A series of strategies to translate these approaches to the diagnosis of renal disease is here proposed. The theoretical and technical problems resulting from the small amount of starting material available from renal biopsies will be specifically addressed. A preliminary study with cDNA array-based expression data obtained from kidneys with tubulointerstitial inflammation and fibrosis suggests the feasibility of distinguishing molecular categories of renal disease. Finally, a combined conventional and molecular work-up of renal biopsies will be suggested. These approaches should add a new dimension to biopsy interpretation and provide novel information concerning renal pathogenesis, diagnosis, prognosis, and differential therapy. A coordinated effort from nephrologists and pathologists in large multicenter trials will be required to achieve this goal. It is hoped that this outlook will lead to stimulating discussions and the implementation of these innovative ideas in nephrology.     

Dominance of virus-specific CD8 T cells in human primary cytomegalovirus infection

Cellular immune responses are of high importance in initiating and maintaining immunity against virus infections. Whereas the cellular immune response during persistent cytomegalovirus (CMV) infection is well assessable, the individual contribution of CD4 and CD8 T cell responses during primary infection has not been described. A novel whole-blood assay, which relies on the flow-cytometric detection of antigen-induced cytokine expression, was used to characterize CMV-specific CD4 and CD8 T cell responses during primary infection of CMV seronegative recipients of a renal allograft from a CMV seropositive donor. These T cell responses were compared with long-term CMV-positive patients with known history of transplantation-related seroconversion. Results were further correlated to CMV load and serum IgG and IgM. The long-term seroconverted patients consistently showed a dominant CMV-specific CD4 T cell response (median frequencies: CD4, 1.12% [range, 0.35 to 8.10%] versus CD8 0.13% [range, <0.05 to 0.55%]). In contrast, during primary infection, the cellular immune response is strongly dominated by CMV-specific CD8 T cells (median peak frequencies: CD4, 1.24% [range, 0.21 to 1.60%] versus CD8, 2.47% [range, 1.34 to 6.67%]). Upon receipt of ganciclovir, viral load as well as CMV-specific CD8 responses decreased. The frequency of the respective CD4 T cells fluctuated during decrease of CMV load and became dominant over CMV-specific CD8 T cell responses. These results are consistent with the view of an effective direct antiviral activity of CD8 T cells, which is most critical during periods of high viremia. Later on during persistent infection, CD4 T cells dominate the immune response to support the state of antiviral immunity.     

Quality of reporting of randomized trials as a measure of methodologic quality

Context  The evaluation of the methodologic quality of randomized controlled trials (RCTs) is central to evidence-based health care. Important methodologic detail may, however, be omitted from published reports, and the quality of reporting is therefore often used as a proxy measure for methodologic quality. We examined the relationship between reporting quality and methodologic quality of published RCTs. Methods  Study of 60 reports of placebo-controlled trials published in English-language journals from 1985 to 1997. Reporting quality was measured using a 25-item scale based on the 1996 issue of the Consolidated Standards of Reporting Trials (CONSORT). Concealment of allocation, appropriate blinding, and analysis according to the intention-to-treat principle were indicators of methodologic quality. Methodologic quality was compared between groups of trials defined by reporting quality scores of low, intermediate, and high. Reporting quality scores were compared between groups defined by high and low methodologic quality. Results  Among 23 trials of low reporting quality (median score, 9 [range, 3.5-10.5]), allocation concealment was unclear for all but 1 trial, but there were 16 trials (70%) with adequate blinding and 9 trials (39%) that had been analyzed according to the intention-to-treat principle. Among 18 trials of high reporting quality (median score, 18 [range 16.5-22.0]), there were 8 trials (44%) with adequate allocation concealment, 16 trials (89%) with adequate blinding, and 13 trials (72%) analyzed according to the intention-to-treat principle. The median reporting score was 15.0 for the 33 trials that were analyzed according to intention-to-treat principle and 14.5 for the 14 trials with on-treatment analyses (P = .67). Conclusions  Similar quality of reporting may hide important differences in methodologic quality, and well-conducted trials may be reported badly. A clear distinction should be made between these 2 dimensions of the quality of RCTs.      

Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with “glioblastoma multiforme”. We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as “short-term” for TTP of less than 6 months (n=54) and “long-term” for TTP of more than 12 months (n=52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastome multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n=7) or anaplastic oligoastrocytoma (WHO grade III, n=2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only progrostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy. Received: 9 November 1999, Received in revised form: 13 January 2000, Accepted: 3 February 2000     

Pressure support ventilation combined with volume guarantee versus synchronized intermittent mandatory ventilation: a pilot crossover trial in premature infants in their weaning phase.

OBJECTIVE: To compare pressure support ventilation combined with volume guarantee (PSV-VG) to synchronized intermittent mandatory ventilation (SIMV) regarding safety, course of blood gases, and infant-ventilator interaction in premature infants. DESIGN: Prospective, two-treatment, crossover pilot study. SETTING: Tertiary care neonatal unit. PATIENTS: Twenty-five ventilated premature infants: median (range) gestational age 26.1 wks (23.1-35.7), birth weight 765 g (450-3170), age at study 5 days (2-27), in their weaning phase. INTERVENTIONS: Infants were studied for three 30-min periods, starting from SIMV, followed by PSV-VG, and back again to SIMV. After concluding the last period, all infants were switched back to PSV-VG. On the next day, infants were studied in the opposite direction. During each period, vital parameters, ventilation parameters, degree of physical activity, duration of rhythmic breathing, and the number of vital signs monitor alarms were recorded. MEASUREMENTS AND MAIN RESULTS: Nineteen infants (84%) could be successfully ventilated with PSV-VG till the next day. PSV-VG achieved a similar oxygenation level as SIMV but with significantly lower ventilation pressures. Comparable ventilation was achieved, but infants with strong respiratory drive were more liable to hyperventilation episodes during PSV-VG. Although infants breathed more rhythmically during PSV-VG, suggesting better infant-ventilator synchrony, the infants' behavioral state and the fluctuations in blood gases did not differ. CONCLUSIONS: The potentials of PSV-VG to improve infant-ventilator synchrony and to decrease pressure needed to ventilate premature lungs are promising, even though the changes were small. However, its benefits during acute illness and on the final outcome remain to be proven.