Brain MR perfusion‐weighted imaging with alternate ascending/descending directional navigation

In this study, a new arterial spin labeling technique that requires no separate spin preparation pulse was developed. Sequential two‐dimensional slices were acquired in ascending and descending orders by turns using balanced steady state free precession for pair‐wise subtraction. Simulation studies showed this new technique, alternate ascending/descending directional navigation (ALADDIN), has high sensitivity to both slow‐ (1–10 cm/sec) and fast‐moving (>10 cm/sec) blood because of the presence of multiple labeling planes proximal to imaging planes and sensitivity of balanced steady state free precession to initial magnetization differences. ALADDIN provided high‐resolution multislice perfusion‐weighted images in ～3 min. About 80–90% of signals in a slice were ascribed to spins saturated in the four prior slices. Three to five edge slices on each side of imaging group were affected by transient magnetization transfer effects and incomplete T₁ recovery between successive acquisitions. ALADDIN signals were dependent on many imaging parameters, implying room for improvement. Sagittal and coronal ALADDIN images demonstrated perfusion direction in gray matter regions was mostly from center to lateral, anterior, or posterior, whereas that in some white matter regions was reversed. ALADDIN is likely useful for many studies requiring perfusion‐weighted imaging with short scan time, insensitiveness to arterial transit time, directional information, high resolution, and/or wide coverage. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Progression of Epididymal Maldevelopment Into Hamartoma-like Neoplasia in VHL Disease

Inactivation of the von Hippel-Lindau (VHL) gene and activation of the hypoxia-inducible factor (HIF) in susceptible cells precedes formation of tumorlets and frank tumor in the epididymis of male VHL patients. We performed detailed histologic and molecular pathologic analysis of tumor-free epididymal tissues from VHL patients to obtain further insight into early epididymal tumorigenesis. Four epididymides from two VHL patients were serially sectioned to allow for three-dimensional visualization of morphologic changes. Areas of interest were genetically analyzed by tissue microdissection, immunohistochemistry for HIF and markers for mesonephric differentiation, and in situ hybridization for HIF downstream target vascular endothelial growth factor. Structural analysis of the epididymides revealed marked deviations from the regular anatomic structure resulting from impaired organogenesis. Selected efferent ductules were represented by disorganized mesonephric cells, and the maldeveloped mesonephric material was VHL-deficient by allelic deletion analysis. Furthermore, we observed maldeveloped mesonephric material near cystic structures, which were also VHL-deficient and were apparent derivatives of maldeveloped material. Finally, a subset of VHL-deficient cells was structurally integrated in regular efferent ductules; proliferation of intraductular VHL-deficient cells manifests itself as papillary growth into the ductular lumen. Furthermore, we clarify that that there is a pathogenetic continuum between microscopic tumorlets and formation of tumor. In multiple locations, three-dimensional reconstruction revealed papillary growth to extend deeply into ductular lumina, indicative of progression into early hamartoma-like neoplasia. We conclude epididymal tumorigenesis in VHL disease to occur in two distinct sequential steps: maldevelopment of VHL-deficient mesonephric cells, followed by neoplastic papillary proliferation.     

Structure-activity relationships of some 3-substituted-4-hydroxycoumarins as HIV-1 protease inhibitors

The screening of the HIV-1 protease (PR) inhibitory activity (IC-50) of various substituted 3-phenyl-4-hydroxycoumarins, 3-benzyl-4-hydroxycoumarins, 3-phenoxy-4-hydroxy-coumarins, 3-benzenesulfonyl-4-hydroxycoumarins and 3-(7-coumarinyloxy)-4-hydroxycoumarins was performed. The data indicate the importance of substituents at positions 5 and 7 of the coumarin ring on the inhibitory potency of the HIV-1-PR.     

Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience

BACKGROUND AND PURPOSE: Despite the widespread use of angioplasty, adjunct chemical therapy is often needed to treat patients with cerebral vasospasm. In this study, we examined the safety of intraarterial administration of verapamil to patients with cerebral vasospasm. We herein summarize our 2-year experience with this treatment. METHODS: We retrospectively reviewed the procedure reports, anesthesia records, clinical charts, and brain images of 29 patients who received intraarterially administered verapamil in 34 procedures for the treatment of vasospasm after subarachnoid hemorrhage from July 1998 to June 2000. The average changes in mean arterial pressure and heart rate were used to measure cardiovascular side effects. The neurologic effects were assessed by angiographic findings, the results of neurologic examinations performed before and after the procedure, and findings of CT of the head. RESULTS: The average dose of verapamil per patient was 3 +/- 0 mg or 44 +/- 5 mcg/kg. The average changes in mean arterial pressure at 10 and 20 minutes were -5 +/- 1 mm Hg and -2 +/- 1 mm Hg or -3.8 +/- 1.0% and -1.7 +/- 1.1%, respectively. No significant change of heart rate was observed at 10 minutes. The patients showed no sign of increased intracranial pressure by hemodynamic parameters, neurologic examination, or CT of the head. On 10 occasions, when the effect of verapamil infusion was assessed angiographically, there was 44 +/- 9% increase of vessel diameter in the spastic segment. Neurologic improvement was noted after five of 17 procedures when verapamil was used as the sole treatment. CONCLUSION: Low dose verapamil is safe when administered intraarterially to patients with cerebral vasospasm. Beneficial effects are achieved in some patients, prompting further study of its efficacy.     

Activation of p44/42 mitogen activated protein kinases in thrombin-induced brain tolerance

BACKGROUND: Our recent studies have shown that prior intracerebral injection of a low dose of thrombin attenuates the brain edema formation that results from either an intracerebral hematoma, an intracerebral injection of a large dose of thrombin or cerebral ischemia. The aim of the current study is to investigate whether thrombin-induced tolerance (thrombin preconditioning; TPC) is associated with activation of p44/42 mitogen activated protein (MAP) kinases. METHODS: This study contained three parts. In the first, rats received an intracerebral infusion of either saline or one unit thrombin (the TPC dose) into the right caudate nucleus. After 1, 3 and 7 days, the rats will be killed and brains used to detect p44/42 MAP kinases activation using Western blot analysis and immunohistochemistry. In the second and third parts, rats received intracerebral infusions of either vehicle, one unit thrombin (TPC) or one unit thrombin and 5 nmol PD 098059. These rats were either killed to detect kinases activation after 24 h or received a second intracerebral infusion of five-unit thrombin 7 days later with brain edema being assessed after a further 24 h. RESULTS: Western blot analysis demonstrated that p44/42 MAP kinases were activated in the ipsilateral basal ganglia after the intracerebral infusion of thrombin one unit. Cells immunoreactive for activated p44/42 MAP kinases were found in the ipsilateral basal ganglia and ipsilateral cortex. PD 098059, a MAP kinase kinase inhibitor, abolished thrombin-induced activation of p44/42 MAP kinases. TPC suppressed thrombin-induced brain edema while PD 098059 blocked this protective effect. The water contents in the ipsilateral basal ganglia 24 h after infusion of thrombin five units were 82.6+/-0.8%, 79.2+/-0.4% and 81.8+/-1.9% in the control, TPC alone and TPC plus PD 098059 groups, respectively. CONCLUSION: Thrombin can activate p44/42 MAP kinases within the brain and the protective effects of thrombin preconditioning on brain edema formation are related to this activation.     

Chloramphenicol-resistant Salmonella typhi in Saigon.

Chloramphenicol-resistant Salmonella typhi was detected in Saigon in September 1971. Subsequently, 163 strains of S typhi were isolated, 46 percent of which were resistant to choramphenicol by the agar-disk method. Sixty-two strains were studied by the broth-dilution method; 37 percent had minimal inhibitory concentrations for chloramphenicol greater than 250mug/ml, but all strains were susceptible to 0.4mug/ml of ampicillin and to a disk of a combination of trimethoprim and sulfamethoxazole (Bactrim). Persons infected with chloramphenicol-resistant strains of S typhi responded poorly to chloramphenicol alone, but ampicillin or the combination drug was effective.     

Arterialization of deep dorsal vein of penis for penile ischemia

Penile ischemia, a rare complication of diabetic end-stage renal disease, is usually treated by penectomy once conservative measures fail. We present a patient with diabetes mellitus and end-stage renal disease with penile ischemia that was successfully treated with an arteriovenous interposition bypass graft between the common femoral artery and the deep dorsal vein of the penis. Retrograde flow into the corpus spongiosum resulted in immediate pain relief and healing of the ischemic lesions.     

Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal-appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT.     

Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.