Adenomatous-Dominant Benign Prostatic Hyperplasia (AdBPH) as a Predictor for Clinical Success Following Prostate Artery Embolization: An Age-Matched Case-Control Study.

PURPOSE: To investigate the clinical impact of performing prostate artery embolization (PAE) on patients with adenomatous-dominant benign prostatic hyperplasia (AdBPH). MATERIALS AND METHODS: Twelve patients from the ongoing proSTatic aRtery EmbolizAtion for the treatMent of benign prostatic hyperplasia (STREAM) trial were identified as having AdBPH; defined as two or more adenomas within the central gland of ≥1 cm diameter on multi-parametric MRI (MP-MRI). These patients were age-matched with patients from the STREAM cohort, without AdBPH. Patients were followed up with repeat MP-MRI at 3 months and 1 year. International prostate symptom score (IPSS), international index for erectile function (IIEF), and quality of life assessment from the IPSS and EQ-5D-5S questionnaires were recorded pre-PAE and at 6 weeks, 3 months, and 1 year. RESULTS: The mean age of patients was 68 (61-76). All patients had PAE as a day-case procedure. The technical success in the cohort was 23/24 (96%). There was a significant reduction in prostate volume following embolization with a median reduction of 34% (30-55) in the AdBPH group, compared to a mean volume reduction of 22% (9-44) in the non-AdBPH group (p = 0.04). There was a significant reduction in IPSS in the AdBPH group following PAE when compared with the control group [AdBPH median IPSS 8 (3-15) vs. non-AdBPH median IPSS 13 (8-18), p = 0.01]. IPSS QOL scores significantly improved in the AdBPH group (p = 0.007). There was no deterioration in sexual function in either group post-PAE. CONCLUSIONS: This is the first time that AdBPH has been identified as being a predictor of clinical success following PAE.

Suspected iatrogenic ureteric injury: an approach to diagnostic imaging.

Iatrogenic ureteric injury (IUI) is the leading cause of ureteric trauma and a complication of major abdominal and pelvic surgery. IUI carries significant morbidity and mortality, which can be further compounded by delayed diagnosis due to its non-specific clinical presentation. We review ureteric anatomy, types of IUI, and imaging strategies available for diagnosis. We propose an imaging protocol for prompt diagnosis and follow-up.

Preparation of polycyclic systems by sequential 5-exo-digonal radical cyclization, 1,5-hydrogen transfer from silicon, and 5-endo-trigonal cyclization.

Radicals of type 1 undergo 5-exo diagonal cyclization, and the resulting vinyl radical abstracts hydrogen from silicon to afford a silicon-centered radical. This radical closes in a 5-endo trigonal manner to generate radicals of type 4, which are reduced (4 --> 5) by stannane, except when the starting acetylene carries a terminal trimethylstannyl group. In this case, radicals 4 expel trimethylstannyl radical to afford vinyl silanes 6. The stereochemical outcome of the radical cascade 1 --> 5 is controlled by the stereochemistry of the oxygen-bearing carbon in 1 (see starred atom). The sequence can be initiated by carbon-, alpha-substituted carbon-, oxyacyl-, and carbamoyl radicals and generates a silicon-containing ring fused onto a carbocycle or heterocycle. Numerous examples are described, as well as a number of transformations of the final cyclization products, especially their response to n-Bu(4)NF and to BF(3).OEt(2), reagents that cleave the newly formed carbon-silicon bond.

Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice.

Centromere protein A (Cenpa for mouse, CENP-A for other species) is a histone H3-like protein that is thought to be involved in the nucleosomal packaging of centromeric DNA. Using gene targeting, we have disrupted the mouse Cenpa gene and demonstrated that the gene is essential. Heterozygous mice are healthy and fertile whereas null mutants fail to survive beyond 6.5 days postconception. Affected embryos show severe mitotic problems, including micronuclei and macronuclei formation, nuclear bridging and blebbing, and chromatin fragmentation and hypercondensation. Immunofluorescence analysis of interphase cells at day 5.5 reveals complete Cenpa depletion, diffuse Cenpb foci, absence of discrete Cenpc signal on centromeres, and dispersion of Cenpb and Cenpc throughout the nucleus. These results suggest that Cenpa is essential for kinetochore targeting of Cenpc and plays an early role in organizing centromeric chromatin at interphase. The evidence is consistent with the proposal of a critical epigenetic function for CENP-A in marking a chromosomal region for centromere formation.

Molybdenum requirements in low-birth-weight infants receiving parenteral and enteral nutrition.

BACKGROUND: Molybdenum (Mo) is an essential trace element required by three enzymatic systems, yet there are no reports of Mo deficiency in infants. Low-birth-weight infants (LBW) might be at risk for Mo deficiency because they are born before adequate stores for Mo can be acquired, they have rapid growth requiring increased intakes, and they frequently receive supplemental parenteral nutrition (SPN) and total parenteral nutrition (TPN) unsupplemented with molybdenum. METHODS: To investigate Mo requirements of LBW infants (n = 16; birth weight, 1336+/-351 g; gestational age, 29.8+/-2.5 weeks; M+/-SD), the authors collected all feeds, urine, and feces prior to TPN (baseline, n = 16, collections = 16), during TPN (n = 9, collections = 19), during SPN (n = 13, collections = 17), and after one week of full oral feeds (FOFs) of formula or human milk (FOF, n = 16, collections = 16). RESULTS: Infant weights at collection times were: 1.3+/-0.3 g, 1.27+/-0.4 g, 1.4+/-0.3 g, and 1.7+/-0.5 g, respectively. Mo intake was 0.03+/-0.1 microg/d, 0.34+/-0.1 microg/d, 1.25+/-1.7 microg/d, and 6.1+/-2.5 microg/d. Mo output was 0.64+/-0.6, 0.34+/-0.5, 0.68+/-0.8, and 4.1+/-2.5 microg/d. Mo balance at these times was -0.60+/-0.5, -0.001+/-0.5, 0.57+/-1.9, and 2.0+/-2.9 microg/d. Mo balance increased with time, yet some infants were always in negative balance, even though Mo intakes exceeded recommendations. CONCLUSIONS: The authors speculate that an intravenous intake of 1 microg/kg/d (10 nmol/kg/d) and an oral intake of 4-6 microg/kg/d (40-60 nmol/kg/d) would be adequate for the LBW infant.

Gene structure and sequence analysis of mouse centromere proteins A and C.

We have determined the genomic structure and organization of the mouse Cenpa and Cenpc genes. CENPA is a member of the histone H3-like proteins and is thought to replace histone H3 in centromeric nucleosomes. CENPC is a DNA-binding protein that is located at the inner kinetochore plate of active mammalian centromeres. The Cenpa cDNA encodes a 134-amino-acid product that is 70% identical and 84% similar to its human homolog. The mouse Cenpa gene is approximately 8 kb in length and contains five exons. Sequence analysis of the 5' DNA sequence of the gene revealed two consensus CAAT boxes, a putative TFIID-binding site, an Sp1-binding domain, and two cell cycle regulatory motifs, but no consensus TATA element. The mouse Cenpc gene spans 60 kb and contains 19 exons that range in size from 44 to 602 bp. Sequence analysis of the C+G-rich promoter region showed the presence of known promoter elements, including a CpG island, a CAAT box, and several GC boxes, but the absence of a consensus TATA element.

Prevalence of rickets in Mongolia.

In order to investigate the current health and nutrition status of mothers and children in Mongolia, a regionally stratified survey of 977 randomly sampled households was conducted during July and August 1997. The prevalence of children aged 6-60 months who demonstrated one or more of three main clinical signs (i.e. rachitic rosary, Harrison's groove and delayed closure of fontanelle) was found to be 69.8%. Although a nationwide supplementation programme exists, caretakers reported only 66.2% of children under 3 years of age had received at least one vitamin D supplement in the 6 months preceding the survey. The lack of adequate UV-B rays during the winter months (i.e. October-April) and traditional swaddling of infants for a minimum of 3 months and a maximum of 9-12 months are likely to contribute to the prevalence of rickets in Mongolia. The high prevalence of rickets in Mongolian children is a serious public health concern. In addition to the adverse effects on growth, development and immune function, it is probably indicative of widespread subclinical vitamin D deficiency.

Chromosomal localization of mouse Cenpa gene.

Using a previously isolated mouse centromere protein A (Cenpa) probe, we have localized the gene to the proximal region of mouse Chromosome 5, between the known Il6 and Yes1 loci near [Adra2C-D5H4S43-Hdh]. Comparison of this localization with that of human CENPA, which maps to chromosome 2, is consistent with the presence of a new region of conserved synteny between the two species.

Short-term plasticity in primary somatosensory cortex of the rat: rapid changes in magnitudes and latencies of neuronal responses following digit denervation.

Recordings were made from neurons in primary somatosensory (SmI) forepaw cortex of rats to study the time course of changes in responses beginning immediately following denervation (ligation) of a single digit. Before denervation, neuronal receptive fields (RFs) defined by tactile stimulation varied in size from small regions of one digit to larger areas covering several digits and palmar pads. With electrical stimulation, most neurons responded best to one (on-focus) digit and less to other (off-focus) digits; on-focus stimulation yielded more spikes per stimulus and shorter spike latencies (Lmin) than did off-focus stimulation. After ligation of the on-focus digit, most neurons showed increased responsiveness to stimulating one or several off-focus digits and palmar regions of the forepaw: (1) tactile stimulation showed that the RFs of all but one neuron expanded to include previously "ineffective" skin regions, such as digits or palmar pads adjoining the original RF; (2) electrical stimulation usually evoked stronger responses from neighboring off-focus digits and sometimes elicited novel responses from previously ineffective digits--seven of ten neurons showed increases in spikes per stimulus, which tended to approach stable values within 60-90 min after denervation; three of ten neurons showed decreases in Lmin with time, but most revealed no significant changes. These results suggest that dynamic response properties, as well as RFs, of SmI cortical neurons can be modified rapidly by blocking afferent input from dominant on-focus skin regions. RFs expand and novel responses appear, with concomitant increases in response magnitude and, in some cases, decreases in response latency over time. These findings seem to reflect a rapid increase in synaptic efficacy of weak or previously ineffective inputs from cutaneous afferent nerve fibers.

Myocardial uptake and washout kinetics of T1-201 with the VEX (vasodilator plus exercise) test: contribution of stress mode components and coronary stenosis severity.

OBJECTIVE: To assess the vasodilator plus exercise (VEX) test as an adjunct to myocardial perfusion imaging with respect to the accuracy of kinetics of thallium-201 (Tl-201) and other indicators of ischemia. SETTING: A nuclear medicine laboratory in which patients referred for myocardial scintigraphy are triaged to undergo the stress component with symptom-limited bicycle exercise, dipyridamole or VEX as appropriate. DESIGN: Cases having correlating scintigraphy and angiography (n = 425) were selected retrospectively. Immediate poststress and redistribution images were quantified using a circumferential profile analysis with interpolative background subtraction. For each of nine sectors on the left anterior oblique image, multivariate analyses were performed, comparing the relative uptake and net washout of Tl-201 to the exercise workload attained, use of dipyridamole, time to redistribution, gender, and the angiographic presence and severity of stenoses at five key sites. Washout values standardized according to gender, exercise level and time to redistribution, were compared with relative uptake profiles and ST depression using receiver operating curves. RESULTS: For each sector, a significant contribution to Tl-201 washout was made by the exercise level (P < 0.001) and by at least one site of stenosis (P < 0.0001), but not by use of dipyridamole (P > 0.5); female gender was associated with increased washout (P < 0.01) except for the three lateral sectors. For each stress modality, standardized washout performed better than ST depression but not as well as relative uptake profiles in detecting coronary artery disease. CONCLUSIONS: For combined pharmacological-exercise stress, quantitative uptake profiles may assist in confirming subjective scan interpretation; washout profiles, even when standardized for gender and stress level, are suboptimal for confirming defect reversibility.

The usefulness of stress tests performed in the nuclear medicine department: mathematical methods to assess efficacy at various angiographic endpoints.

Stress myocardial perfusion scintigraphy (SMPS) may be used to amplify or supplant information available from stress electrocardiography (ECG) in directing the clinical management of patients, including the need for coronary angiography. The apparent usefulness of SMPS may depend on referral bias, the stress mode employed and the criterion for disease. We compared markers of ischaemia on quantitative planar SMPS with 201 Tl in 503 referred patients; stress was tailored to the individual patient to include exercise (n = 154), dipyridamole (n = 118) or a combination of the two (n = 231). Four angiographic criteria of increasing severity (A-D) were targeted. The fraction of the population receiving diagnostic benefit was calculated for reversible defects (RD) or lung uptake (LU) in comparison to concurrent ST depression; abnormal baseline tracings and fixed 201Tl defects were regarded as indeterminate. Decision tree induction, a computer-learning algorithm and logistic regression were also used to assess the contribution of 13 scintigraphic and other input variables. In comparison to ST depression, RD showed incremental value in 167 (33%) patients with criterion A, decreasing to 5% with criterion D; LU showed its greatest benefit (21%) with criterion D. Both scintigraphic markers were more useful with dipyrida-mole-based tests than with exercise alone. Decision trees induced at each criterion for disease showed the predominant contribution of scintigraphic results in comparison to clinical and ECG data. In conclusion, in a referred population with a frequent requirement for pharmacological stress, the clinical utility of scintigraphy can be determined by comparison of markers of ischaemia; the results will depend, however on the angiographic criterion for disease.

Critical stenoses of the left anterior descending artery: predominant role in stress-induced pulmonary uptake of 201thallium.

OBJECTIVE: To relate the diagnostic finding of stress-induced pulmonary uptake of 201thallium to the severity and site of stenoses in specific coronary arteries. DESIGN: An ad hoc series of 525 referred cases had planar myocardial perfusion scintigraphy studies within four months of correlating invasive studies; patients who had previous revascularization procedures were excluded. MEASUREMENTS: Invasive studies were read by a cardiovascular radiologist with rating of stenoses as percentage luminal diameter, and grading of ventricular function from 1 (normal) to 5 (globally hypokinetic). Lung:myocardial ratios were quantitated independently on immediate poststress 201thallium myocardial perfusion images by a nuclear medicine physician. Multivariate regression equations were used to relate pulmonary uptake to stenoses in specific arteries and to the degree of ventricular dysfunction. RESULTS: Lung:myocardial ratios showed only a minor relationship to the number of subcritical (less than 90%) stenoses, but were considerably increased when severe (at least 90%) stenoses were present. Severe stenoses in the left anterior descending artery (LAD), particularly its proximal portion, provided the most dramatic increase in this index, modified by the contrast ventriculography score and to a lesser extent by additional stenoses at other sites. Regression analysis suggested a weighting of lesions in the LAD or left mainstem by a factor of at least 3 in comparison with the right coronary and left circumflex arteries. CONCLUSIONS: Stenoses in the LAD, particularly its proximal position, play a key role in the induction of increased pulmonary uptake of 201thallium on poststress scintigrams.

Postarteriographic femoral pseudoaneurysms: treatment with ultrasound-guided compression.

Pseudoaneurysms following femoral arterial catheterization are increasingly common and are related to factors such as catheter size, periprocedural anticoagulation, hypertension, and improper technique. Ultrasound-guided compression as a noninvasive technique for repair of these lesions was prospectively evaluated in 16 patients whose mean age was 61 years. Nine patients were on anticoagulants and six had hypertension. All patients presented with an enlarging groin hematoma, a pulsatile mass, and/or a bruit following femoral catheterization. Seventeen femoral artery pseudoaneurysms, including one with an associated arteriovenous fistula, were detected using color-flow Doppler imaging. Three pseudoaneurysms thrombosed spontaneously. The remaining 14 were managed with compressive therapy lasting from 20 to 100 minutes. No complications were encountered during the compressions and 10 false aneurysms (71%) responded completely (mean time to thrombosis of 38 minutes). Two lesions responded partially to compression and there were two failures, the latter associated with excessive anticoagulation in one patient and a well-established pseudoaneurysm in the second patient. Only one pseudoaneurysm (6%) in the series required surgical correction. Ultrasound-guided compression of acute pseudoaneurysms in the groin is a safe, inexpensive, and effective method of treatment.

Markers of left ventricular dysfunction induced by exercise, dipyridamole or combined stress on ECG-gated myocardial perfusion scans.

An index of left ventricular contraction can be extracted from the cavitary time-activity curve of electrocardiographic (ECG)-gated myocardial perfusion scans. To assess the induction of stress-induced myocardial depression, we compared contraction indexes derived from immediate poststress and delayed 201Tl images with indexes of ventricular dilation and lung uptake in the prediction of severe coronary artery disease (defined as two or more 90% stenoses). Stress procedures were performed in 93 patients with symptom-limited supine bicycle exercise alone, and in 227 with intravenous dipyridamole, combined where possible with exercise. The immediate and delayed contraction indexes reflected left ventricular dysfunction on ventriculography (P < 0.0001), but additionally the immediate index was reduced (P < 0.0001) in severe coronary disease. Stress-induced hypokinesis was seen frequently after each of the test modes. The relationship with angiographic findings was better defined for indexes of contraction than for lung uptake or ventricular dilation (P < 0.01). The prediction of severe coronary disease was optimized by combining the poststress contraction index and lung uptake. These data support the use of ECG-gated myocardial scans in evaluating the functional consequences of stress/imaging procedures.

Pulmonary thallium-201 uptake following dipyridamole-exercise combination compared with single modality stress testing.

Angiographic and clinical determinants of pulmonary uptake of thallium-201 were assessed in a laboratory setting where supine bicycle exercise is used for stress testing in the absence of limiting pharmacologic or physical factors, and where symptom-limited exercise is added to intravenous dipyridamole infusion in other cases. Angiographic correlation was available in 400 patients, including 130 tested with exercise, 94 in whom only handgrip or abbreviated bicycle exercise could be used after dipyridamole, and 176 in whom intravenous dipyridamole was combined with a significant level of exercise. For each test mode, lung/myocardial ratios on the immediate image were highly correlated (p less than or equal to 0.001) with a score based on the number of critical coronary artery stenoses, with grading by contrast ventriculography, and with the number of stenosed (greater than or equal to 50%) arteries; relationships (p less than 0.05) to history of myocardial infarction and to gender were also present. Multiple regression analysis showed the critical stenosis score and ventricular dysfunction to be the only significant determinants. When dipyridamole based tests were compared with exercise, curves of receiver-operating characteristics showed a tendency to better diagnostic performance. When dipyridamole is incorporated in stress testing, the value of increased lung uptake as an ancillary diagnostic sign is similar to that established for exercise.

Ischemic left ventricular dysfunction assessed on ECG-gated thallium-201 myocardial perfusion images.

Ischemic dysfunction of the left ventricle can be suggested by ancillary data derived from thallium-201 myocardial perfusion images. In this study, qualitative and quantitative assessments of global and segmental contraction derived from ECG-gated left anterior oblique images were analyzed to define more precisely transient ischemic hypokinesis. Immediate (4 mins post stress) and delayed (2 to 4 h) images were compared in 200 patients; 165 had coronary angiography and 35 had a low probability of coronary artery disease based on pretest and test outcome variables. For both immediate and delayed images, a quantitative index of left ventricular contraction (derived from the time-activity curve of the left ventricular cavity and validated in a previous study), correlated well with contrast ventriculography scores. The index derived from the immediate image also was related to the severity/extent of coronary artery lesions and to thallium-201 lung uptake. The ratio of indices (immediate/delayed) was depressed (P less than 0.001) in patients with two or three critically diseased vessels, and reflected the qualitative assessment of stress-induced dysfunction on cinematic images. These data suggest that the quantitative index derived from ECG-gated perfusion scans may be a valuable indicator of stress-induced ventricular contractile dysfunction.

Dipyridamole combined with symptom-limited exercise for myocardial perfusion scintigraphy: image characteristics and clinical role.

Although dipyridamole can be used with myocardial scintigraphy to demonstrate reversible perfusion defects, combining exercise with the pharmacologic tool could improve image quality and information yield. The incidence of perfusion defects and the quality of thallium 201 images were reviewed in a series of 820 patients who had been assigned to a specific stress-test mode. Supine bicycle exercise alone was used (group I) where no pharmacologic or physical factors (e.g., beta-blockers, arthritis) limited performance; otherwise, intravenous dipyridamole was followed by symptom-limited exercise (group II). Angiographic correlation was available in 57 patients in group I, and in 158 in group II; of these, 109 performed significant exercise (greater than or equal to 3 min at increasing workloads) following dipyridamole (group IIA), whereas in 49 (group IIB) the exercise phase following dipyridamole was truncated. All test-mode groups were similar with respect to the incidence of ST segment depression during testing, patient throughput, and the sensitivity of perfusion defects. Chest pain and reversible defects were induced more frequently in group II than in group I. In group IIA, splanchnic background activity was lower (P less than 0.001) than in group IIB, and the false-positive rate tended to be lower. Thus, combining exercise with dipyridamole in patients with non-cardiac limitations to exercise enabled the achievement of optimal results for perfusion scintigraphy.

Quantitative analysis of myocardial ischaemia on end-diastolic thallium 201 perfusion images.

ECG gating of images with thallium 201 (201Tl) may improve the representation of myocardial perfusion by allowing isolation of the end-diastolic (ED) portion of the cardiac cycle. To characterize this phenomenon, circumferential distribution profiles for ED and conventional total-cycle images (TC) with 201Tl were analysed after summing ECG gated acquisitions; redistribution was defined as net washing of 201Tl for specific myocardial segments visualized on the left anterior oblique images. Scintigraphic data were compared with the presence of coronary stenoses in 150 patients. ED images had relatively less activity in the inferoseptal and inferoapical region than TC profiles. The ED mode of washout analysis provided more frequent confirmation of visually suggested redistribution than did the TC mode (84% incidence of net wash in for ED, 69% for TC). ED analysis showed a higher incidence of net 201Tl wash in in relation to critical circumflex and left anterior descending artery lesions, but yielded a similar overall performance to TC analysis in distinguishing patients with diseased coronary arteries from normal subjects. Thus, in selected cases, analysis of ED images could assist in confirming 201Tl redistribution.

Estimation of left ventricular function on ECG-gated thallium-201 myocardial perfusion images.

ECG-gated thallium-201 perfusion images (GT) may provide information concerning left ventricular contraction. To assess the objectivity of this information, qualitative and quantitative evaluations of left anterior oblique GT images were performed in 600 patients and compared with contrast ventriculography (n = 180) and gated blood pool scintigraphy (n = 60). Cinematic playback of GT allowed qualitative rating of ventricular performance in 98% of studies. Abnormal GT (focal or global hypokinesis) was found in 41% of cases and could be related to myocardial infarction, nonischemic cardiomyopathy or left bundle branch block. Blinded readings showed reasonable interobserver agreement and correlation with blood pool scintigraphy regarding segmental and overall left ventricular function; decreased tracer uptake in an abnormally perfused segment presented only occasional difficulty. A quantitative index was derived by relating the increment in left ventricular cavity activity during contraction to myocardial count density; results were expressed as a planar ejection fraction (PEF). PEF correlated well with ejection fraction on blood pool scintigraphy (r = 0.83, P less than 0.001) and with contractility scores derived from ventriculography (P less than 0.001) and seemed suited for identification of hypokinetic ventricles. Thus, GT allows objective estimation of left ventricular function as an addendum to myocardial perfusion imaging.