Accuracy and feasibility of contrast echocardiography for detection of perfusion defects in routine practice: comparison with wall motion and technetium-99m sestamibi single-photon emission computed tomography. The Nycomed NC100100 Investigators

OBJECTIVES: We sought to assess the feasibility and accuracy of myocardial contrast echocardiography (MCE) using standard imaging approaches for the detection of perfusion defects in patients who had a myocardial infarction (MI). BACKGROUND: Myocardial contrast echocardiography may be more versatile than perfusion scintigraphy for identifying the presence and extent of perfusion defects after MI. However, its reliability in routine practice is unclear. METHODS: Fundamental or harmonic MCE was performed with continuous or triggered imaging in 203 patients with a previous MI using bolus doses of a perfluorocarbon-filled contrast agent (NC100100). All patients underwent single-photon emission computed tomography (SPECT) after the injection of technetium-99m (Tc-99m) sestamibi at rest. Quantitative and semiquantitative SPECT, wall motion and digitized echocardiographic data were interpreted independently. The accuracy of MCE was assessed for detection of segments and patients with moderate and severe sestamibi-SPECT defects, as well as for detection of patients with extensive perfusion defects (>12% of left ventricle). RESULTS: In segments with diagnostic MCE, the segmental sensitivity ranged from 14% to 65%, and the specificity varied from 78% to 95%, depending on the dose of contrast agent. Using both segment- and patient-based analysis, the greatest accuracy and proportion of interpretable images were obtained using harmonic imaging in the triggered mode. For the detection of extensive defects, the sensitivity varied from 13% to 48%, with specificity from 63% to 100%. Harmonic imaging remained the most accurate approach. Time since MI and SPECT defect location and intensity were all determinants of the MCE response. The extent of defects on MCE was less than the extent of either abnormal wall motion or SPECT abnormalities. The combination of wall motion and MCE assessment gave the best balance of sensitivity (46% to 55%) and specificity (82% to 83%). CONCLUSIONS: Although MCE is specific, it has limited sensitivity for detection of moderate or severe perfusion defects, and it underestimates the extent of SPECT defects. The best results are obtained by integration with wall motion. More sophisticated methods of acquisition and interpretation are needed to enhance the feasibility of this technique in routine practice.     

Sources of acetyl-CoA entering the tricarboxylic acid cycle as determined by analysis of succinate 13C isotopomers

A new 13C NMR technique for measuring substrate utilization by the citric acid cycle based on an analysis of succinate 13C isotopomers is presented. The relative contribution of up to three different labeling patterns in acetyl-CoA entering the citric acid cycle may be determined under non-steady-state conditions. We present experimental data from perfused rat hearts subjected to a brief period of ischemia, where both succinate and glutamate resonances were observed in the 13C spectrum. The contributions of labeled exogenous acetate and lactate and unlabeled sources to the acetyl-CoA pool were compared using this succinate analysis and a previously published glutamate analysis [Malloy et al. (1990) Biochemistry 29, 6756-6761], and the two methods give identical results. This indicates that the succinate and glutamate isotopomers originated from a common alpha-ketoglutarate pool, verifying that glutamate is in isotopomeric equilibrium with alpha-ketoglutarate under these conditions.     

Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol): effects on the pharmacokinetics of liposomal vincristine

The cost-benefit ratio of tetravalent rhesus rotavirus vaccine (RRV-TV) in Finland for prevention of rotavirus gastroenteritis was assessed in a randomized, double-blind, placebo-controlled trial. Costs related to vaccination, side effects, and gastroenteritis were identified. Children received RRV-TV (n = 1,191) or placebo (n = 1,207) at 2, 3, and 5 months of age with other infant vaccinations. Prospective follow-up averaged 1.0 years per child. An intention-to-treat analysis was performed from the perspective of society. Nine cases of severe rotavirus gastroenteritis occurred in the RRV-TV group, versus 100 in the placebo group (P < .0001); mean cost per vaccinated child was 4 Finnish marks (FIM) in the RRV-TV group, versus 203 FIM in the placebo group. Side effects with related costs occurred after 11% and 7% of doses in the RRV-TV group and placebo group, respectively (P < .001); mean cost per child was 89 FIM vs. 75 FIM. The break-even cost (i.e., net benefit, excluding cost of vaccine) of RRV-TV in prevention of severe rotavirus gastroenteritis was 109 FIM (U.S. $19.60) per child.     

Lateral cephalometric analysis of asymptomatic volunteers and symptomatic patients with and without bilateral temporomandibular joint disk displacement

Anecdotal evidence links silicone gel breast implants with the development of autoimmune connective tissue disease in women. To investigate whether silicone gel is capable of directly inducing and/or enhancing the development of autoimmune disease, female BALB/cAnPt (BALB/c) and New Zealand Black (NZB) mice were injected subcutaneously with silicone gel, pristane, a nonmetabolizable substance that can cause plasmacytomas in BALB/c and NZB mice, or saline and monitored for the development of glomerulonephritis and autoantibody production. NZB, but not BALB/c, mice spontaneously develop autoantibodies and an autoimmune hemolytic anemia by 12 months of age. Over a period of 10 months, biweekly screening for proteinuria revealed increases in urinary protein in NZB mice that received multiple injections of either silicone gel or pristane. In contrast, urinary protein was unaffected in identically treated BALB/c mice. Although, silicone gel had no effect on serum titers of antierythrocyte antibodies in NZB mice, the hematocrits were significantly decreased. Moreover, silicone gel both increased the concentration of IgM anti-type I collagen antibodies and skewed the immunofluorescent staining pattern of serum autoantibodies on HEp-2 cells. In contrast, silicone gel failed to induce the production of anti-erythrocyte or antinuclear antibodies in BALB/c mice and induced only slight increases in IgG anti-type I collagen antibodies. These results suggest that silicone gel can exacerbate the development of autoimmune disease in autoimmune NZB mice, but fails to induce disease in normal BALB/c mice. This is consistent with several epidemiological studies failing to demonstrate an increase in the incidence of autoimmune disease in women with breast implants. However, because silicone gel was able to exacerbate autoimmune disease in NZB mice, it may play a similar role in the development of autoimmune disease in a small percentage of women who are genetically susceptible to such diseases.     

Short-wavelength automated perimetry and retinal nerve fiber layer evaluation in suspected cases of glaucoma

OBJECTIVES: To determine if short-wavelength automated perimetry (SWAP) provides evidence that indicates early functional losses in ocular hypertensive subjects and to establish a direct comparison with early structural abnormalities in the retinal nerve fiber layer (RNFL). METHODS: A total of 160 eyes belonging to 83 patients with ocular hypertension (intraocular pressure >21 mm Hg and normal results on standard automated perimetry evaluation), on which a SWAP and RNFL study were performed, were examined. One hundred twenty-eight age-matched subjects without ocular hypertension were evaluated to establish the 95% and 99% confidence intervals at each of the 76 exploration points of the SWAP test. RESULTS: The RNFL study results were normal in 83 cases (51.8%) and pathologic in 77 cases (48.1%). The SWAP results were pathologic in 57 cases (35.6%). Significant differences (P<.001) were observed when comparing the distribution of normal and pathologic SWAP results among the types of defects in the RNFL (focal wedge, diffuse atrophy, and mixed atrophy). CONCLUSIONS: Short-wavelength automated perimetry is a useful test for the early detection of visual field losses. It is more sensitive than standard automated perimetry and provides a high association with RNFL assessment, which has proved capable of detecting signs of glaucomatous damage several years before the onset of the typical visual field defects.     

Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion

Leptin is a protein that is produced primarily in fat tissue and is thought to be a lipostatic feedback signal for the regulation of body fat stores. The purpose of this study was to determine the behavioral specificity of i.c.v.-administered mouse leptin in rats and to assess the effects on meal patterns. Using a modified two-bottle paradigm we examined the putative aversive response to i.c.v. doses of 1, 5, 7, 10, and 30 microg of mouse leptin. Artificial CSF and intraperitoneal lithium chloride served as negative and positive controls, respectively. Saccharin consumption in all leptin treatments was not significantly different from the negative control. Following a recovery period, rats from the same group were used to assess the effects of a 30-microg i.c.v. dose on cumulative food intake and meal patterns using a computer-based system for acquisition of feeding data. Leptin (i.c.v.) significantly increased intermeal interval and decreased meal size. We, therefore, conclude that mouse leptin, at doses up to 30 microg i.c.v., is not aversive in the rat, and that leptin has a multiphasic effect on meal patterns.     

Hereditary form of parkinsonism--dementia

In four generations of a family, 13 members were afflicted with an autosomal dominant disorder characterized by young age at onset, early weight loss, and rapidly progressive dopa-responsive parkinsonism, followed later by dementia and, in some, by hypotension. Intellectual dysfunction began with subjective memory loss and objective visuospatial dysfunction and was followed later by decline of frontal lobe cognitive and memory functions. Neuropathological examination in 4 autopsied cases showed neuronal loss in the substantia nigra and locus ceruleus and widespread Lewy bodies, many of them in the cerebral cortex; those in the hypothalamus and locus ceruleus were often of bizarre shapes. Other findings were vacuolation of the temporal cortex, unusual neuronal loss and gliosis in the hippocampus (CA 2/3), and neuronal loss in the nucleus basalis. There were no neuritic plaques, neurofibrillary tangles, or amyloid deposits. Positron emission tomography in 3 patients showed decreased striatal uptake of fluorodopa. Neurochemical analysis of an autopsied brain showed a pronounced decrease in choline acetyltransferase activity in the frontal and temporal cortices and hippocampus and a severe depletion of striatal dopamine with a pattern not typical of classic Parkinson's disease.     

Complete and partial XY sex reversal associated with terminal deletion of 10q: report of 2 cases and literature review

We describe 2 karyotypically male infants with terminal deletion of 10q and mental retardation, multiple phenotypic anomalies and abnormal genitalia. One [karyotype 46,XY, del(10)(q26.1)] had female external genitalia; the other [karyotype 46,XY,-10,+der(10)t (10;16)(q26.2;q21)] had an intersex phenotype. Of 8 males previously reported with terminal 10q deletion as the major or only cytogenetic abnormality, 2 had an intersex phenotype, and the others all had combinations of cryptorchidism, micropenis, and hypospadias. Terminal 10q deletions appear to be strongly associated with abnormal male genital development, and should be specifically searched for in the cytogenetic workup of such cases.     

Electromagnetic fields influence NGF activity and levels following sciatic nerve transection

Activated neutrophils play an important role in reperfusion injury following hepatic ischemia. Neutrophil elastase is a powerful proteolytic enzyme. We investigated the possibility that ONO-5046. Na, which is a new recombinant-specific neutrophil elastase inhibitor, can reduce ischemia and reperfusion injury in the canine liver. Adult mongrel dogs (n = 19) were used in this experimental study. Seventy-five percent of the liver was resected after 60 min of vascular occlusion. The animals were divided into two groups. The ONO group (n = 8) was given ONO-5046. Na dissolved in saline starting 30 min prior to clamping the hepatic inflow and continuing for 4 h after reperfusion at a rate of 10 mg/kg/h. The nontreatment group (n = 11) received a saline solution for the same period. ALT and LDH levels were significantly lower (P < 0.05) in the ONO group than in the nontreatment group after reperfusion. Purine nucleoside phosphorylase and hyaluronic acid levels, which are markers of endothelial damage, were significantly lower (P < 0.05) in the ONO group than in the nontreatment group after reperfusion. Histologically, widely spread hepatocyte necrosis was found in dogs in the nontreatment group that died prematurely. Neutrophil infiltration of the sinusoids was less evident in the ONO group than in the nontreatment group. Neutrophil elastase inhibitor may prevent injuries of both endothelial and parenchymal cells in extended hepatectomy with vascular occlusion.