De novo trisomy 16p11.2-qter: report of an infant

We report on a four-month-old girl with a de novo trisomy 16q [47,XX, +del(16)(p11.2).ish del(16)(p11.2)(wcp16+,D16Z2+,tel16q+, tel16p-)]. She had minor facial anomalies, limb anomalies, urogenital abnormalities, and severe cardiovascular defects. Autopsy confirmed left hypoplastic lung, total anomalous pulmonary venous drainage via coronary sinus, persistent left superior vena cava, patent ductus arteriosus, secundum atrial septal defect, bilateral hydronephrosis and hydroureters, uterus bicornis, and ovarian hypoplasia. Short tandem repeat polymorphism analysis indicated that the additional, structurally abnormal chromosome 16 was maternal in origin.     

Cerebral hemodynamics and metabolism in adult moyamoya disease: Comparison of angiographic collateral circulation

PURPOSE: The extent of the hemodynamic and metabolic impairments in adult patients with moyamoya disease is still controversial. The aim of the present study was to evaluate the hemodynamic and metabolic status in relation to the development of basal moyamoya vessels (BMVs). METHODS: The cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV) were measured using PET in ten patients with ischemic adult moyamoya disease (mean age, 36.6 years) and six age-matched normal controls (mean age, 33.3 years). The cerebrovascular reserve (CVR) after acetazolamide (ACZ) loading was also estimated using iodine-123 N-isopropyl-p-iodo amphetamine single photon emission computed tomography (123I-IMP SPECT). RESULTS: Based on the angiographic findings, eleven cerebral hemispheres with well-developed BMV (extensive BMV hemispheres) and nine cerebral hemispheres with diminished BMV (diminished BMV hemispheres) were identified. The main routes of collateral circulation in extensive BMV hemispheres were BMVs and leptomeningeal anastomoses. On the other hand, in diminished BMV hemispheres, transdural anastomosis was predominant, and leptomeningeal anastomoses were less developed. In cortices distal to the occluded internal carotid artery, the extensive BMV hemispheres exhibited a significantly lower CBF, CMRO2, CBF/CBV, and CVR (p < 0.05) and a significantly higher CBV and OEF than in diminished BMV hemispheres and controls (p < 0.05). Except for the CBF in the white matter, the mean hemodynamic and metabolic parameters of the diminished BMV hemispheres were not significantly different from those of the controls. CONCLUSION: The extensive development of basal moyamoya vessels is a sign of severe hemodynamic impairment in adult patients with ischemic moyamoya disease. The results may not apply to adults with hemorrhagic onset.     

PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.     

Reactivity of hydroxybenzoic acids in the hydrogen-isotope exchange reaction.

The hydrogen-isotope exchange reaction (T-for-H exchange reaction) between tritiated water vapor (HTO vapor) and 3-hydroxy-4-methoxybenzoic acid (and it's analog; 4-hydroxy-3-methoxybenzoic acid) were observed at 50 and 70 degrees C in a gas-solid system to reveal the reactivity of a functional group in an aromatic compound having two substituents in the aromatic ring. Further, it was shown that (a) the reactivity of the compounds used in this work follows the Hammett's rule, and (b) the reactivity of trisubstituted aromatic compound could be analyzed by applying the additive property of the Hammett's rule even if the compound contains a substituent at the ortho-position.     

Diagnostic performance of fluorodeoxyglucose positron emission tomography/magnetic resonance imaging fusion images of gynecological malignant tumors: comparison with positron emission tomography/computed tomography

Purpose

We compared the diagnostic accuracy of fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and PET/magnetic resonance imaging (MRI) fusion images for gynecological malignancies.

Materials and methods

A total of 31 patients with gynecological malignancies were enrolled. FDG-PET images were fused to CT, T1- and T2-weighted images (T1WI, T2WI). PET-MRI fusion was performed semiautomatically. We performed three types of evaluation to demonstrate the usefulness of PET/MRI fusion images in comparison with that of inline PET/CT as follows: depiction of the uterus and the ovarian lesions on CT or MRI mapping images (first evaluation); additional information for lesion localization with PET and mapping images (second evaluation); and the image quality of fusion on interpretation (third evaluation).

Results

For the first evaluation, the score for T2WI (4.68 ± 0.65) was significantly higher than that for CT (3.54 ± 1.02) or T1WI (3.71 ± 0.97) (P < 0.01). For the second evaluation, the scores for the localization of FDG accumulation showing that T2WI (2.74 ± 0.57) provided significantly more additional information for the identification of anatomical sites of FDG accumulation than did CT (2.06 ± 0.68) or T1WI (2.23 ± 0.61) (P < 0.01). For the third evaluation, the three-point rating scale for the patient group as a whole demonstrated that PET/T2WI (2.72 ± 0.54) localized the lesion significantly more convincingly than PET/CT (2.23 ± 0.50) or PET/T1WI (2.29 ± 0.53) (P < 0.01).

Conclusion

PET/T2WI fusion images are superior for the detection and localization of gynecological malignancies.     

Determination of molecular species composition of C80 or longer-chain alpha-mycolic acids in Mycobacterium spp. by gas chromatography-mass spectrometry and mass chromatography

The molecular species composition of alpha-mycolic acids ranging from C68 to C86 in 13 rapidly growing and 12 slowly growing mycobacterial species was determined by gas chromatography, gas chromatography-mass spectrometry, and mass chromatography. In gas chromatographic analysis, the molecular species of alpha-mycolic acids were well separated as trimethylsilyl ether derivatives of the methyl esters, according to their total carbon numbers. The total carbon and double-bond numbers of mycolic acids at each peak on gas chromatograms were determined from the [M]+, [M - 15]+, and [M - 90]+ ions on the mass spectrum, and straight and branched chain structures were identified by the mass fragment ions [A]+, due to C2--C3 cleavage [R-CH-O-Si(CH3)3]+, and [B]+, due to C3--C4 cleavage [(CH3)3-Si-O-CH-CH(R')-COOCH3]+. The concentration of odd- and even-carbon-numbered mycolic acids, which often overlap each other on gas chromatograms, and the composition of three homologous mycolic acids with different alpha units (C22:0, C24:0, and C26:0) were clearly determined by mass chromatography monitoring [M - 15]+ ions and [B - 29]+ ions, respectively. The molecular species composition of alpha-mycolic acids and their average carbon numbers (av. cn.) as a simple expression of the composition were calculated from the mass chromatograms. Each mycobacterial species examined was demonstrated to possess a characteristic profile of alpha-mycolic acid composition, and based on this the species were classified approximately into eight groups: C68 to C76 (av. cn. 72), dienoic, possessing a C20 alkyl branch at the 2 position (C22 alpha-unit) for Mycobacterium diernhoferi and Mycobacterium sp. strain 3707, a chromogenic rapid grower; C72 to C78 (av. cn. 75), dienoic with both C22 and C24 alpha units, containing a small or a large amount of odd-carbon-numbered molecules, for M. vaccae, M. rhodesiae, and M. phlei (chromogenic rapid growers); C72 to C80 (av. cn. 75 to 77), dienoic with C24 alpha-unit, containing a moderate or a large amount of odd-carbon-numbered molecules, for M. smegmatis, M. chitae, M. chelonae (M. chelonei), and M. fortuitum (nonchromogenic rapid growers); C78 to C82 (av. cn. 80), even-carbon-numbered dienoic with C24 alpha unit for M. agri and M. thermoresistible (rapid growers); C75 to C81 (av. cn. 77 to 79), odd-carbon-numbered dienoic with C24 alpha unit for M. nonchromogenicum complex (M. nonchromogenicum, M. terrae, and "M. novum") (slow growers); (vi) C76 to C84 (av. cn. 79 to 81), even-carbon-numbered dienoic with C24 alpha unit for MAIS complex including M. scrofulaceum, M. avium, and M. intracellulare (slow growers); (vii) C72 to C80 (av. cn. 77 to 79), even-carbon-numbered dienoic with C24 alpha unit for M. szulgai, M. gordonae, and M. kansasii (chromogenic slow growers); and (viii) C76 to C86 (av. cn. 79 to 81), even-carbon-numbered dienoic with C26 alpha unit M. bovis Ravenol and BCG and M. tuberculosis H37Rv. This study demonstrated that gas chromatography-mass spectrometric analysis of the molecular species composition of alpha-mycolic acid can give rapid, important, and very precise information for the identification of pathogenic and nonpathogenic mycobacterial species.     

Attenuated forearm vasodilative response to intra-arterial atrial natriuretic peptide in patients with heart failure

It has been shown that renal responses to atrial natriuretic peptide (ANP) are markedly attenuated in patients with heart failure. This study aimed to determine if vasodilative response to ANP is altered in patients with heart failure. In patients with heart failure (n = 7) and age-matched normal subjects (n = 7), forearm blood flow was measured using a strain-gauge plethysmograph during intra-arterial infusion of alpha-human ANP (50, 100, 200, and 400 ng/min) or nitroglycerin (100, 200, 400, and 600 ng/min). Forearm vasodilatation evoked with intra-arterial alpha-human ANP in patients with heart failure was considerably less (p less than 0.01) than that in normal subjects. In contrast, nitroglycerin produced comparable forearm vasodilatation in the two groups. Plasma ANP and cyclic guanosine monophosphate (GMP) levels at rest were higher in patients with heart failure than in normal subjects (p less than 0.05 for both), but the increases in plasma ANP and cyclic GMP in the venous effluents during intra-arterial ANP infusion did not differ between the two groups. These results indicate that the direct vasodilative effect of ANP on forearm vessels was attenuated in patients with heart failure as compared with that in normal subjects. The mechanisms responsible for this alteration are not clear but might involve mechanisms other than down-regulation of the ANP receptors because the increases in venous plasma cyclic GMP caused by intra-arterial ANP were comparable between patients with heart failure and normal subjects.     

Factors causing prolonged hypoperfusion after transient ischemic attack

Even during the symptom-free stages, patients with a TIA often experience cerebral blood flow disturbances. In order to evaluate the factors which cause this abnormality, we studied the cerebral blood flow disturbance, anatomy and clinical status in 21 patients after TIAs. The results of^99mTc-hexamethyl-propylene-amine oxime SPECT were compared with CT, cerebral angiogram, cerebrovascular risk factors and clinical findings to determine which factor is most responsible for the hypoperfusion of brain after TIA. The overall sensitivity rates in detecting a lesion were 67% in SPECT and 19% in CT. The hypoperfused area tended to be large in patients who had intracranial, severe stenotic, multiple, or hemodynamically significant arterial lesions on the ipsilateral side. No such relationships were found between other examinations. We conclude that hypoperfusion after TIA essentially reflects a continuous cerebral blood flow disturbance that can be attributed to atherosclerosis of the cerebral arteries, with subsequent embolic and/or hemodynamic cerebral ischemia, although there may be a variety of processes.