2-[18F]-2-deoxy-D-glucose (FDG) uptake in human tumor cells is related to the expression of GLUT-1 and hexokinase II.

BACKGROUND: The uptake of 2-[18F]-2-deoxy-D-glucose ((18)F-FDG) is widely used as a marker of increased glucose metabolism to monitor progression of cancers with positron emission tomography (PET). Many tumors have been shown to overexpress facilitated glucose transporters, especially GLUT-1 and a glycolytic enzyme, hexokinase II. PURPOSE: To define whether a quantitative relationship exists between the expression levels of GLUT-1 and hexokinase II, and (18)F-FDG uptake in human cancer xenografts. MATERIAL AND METHODS: We determined the expression levels of both GLUT-1 and hexokinase II in normal cells and in five different human cancer cell lines (AGS, A431, A549, Colo 320 HSR, and HepG2) using Western blot analysis. In vitro assays of 18F-FDG uptake in cultures were performed, and subsequently representative cell lines were inoculated onto the flanks of severe combined immunodeficient (SCID) mice. To establish an orthotopic model of human hepatocellular carcinoma (HCC), cells were injected into the intraportal vein of SCID mice. (18)F-FDG uptake in vivo was assessed by subjecting mice to PET imaging. RESULTS: All cell lines were shown to express higher amounts of GLUT-1 and hexokinase II compared with fibroblast controls. Our results from in vitro (18)F-FDG uptake assays also correlated with the Western blot results. All xenografts gave highly positive results at microPET imaging, and a strong correlation (R(2)=0.88, P<0.001) was found between the maximum standardized uptake values (SUV(max)) and the expression of GLUT-1 proteins. CONCLUSION: Our data indicate that the expression levels of GLUT-1 and hexokinase II as well as in vitro assays of FDG uptake serve as good screening tests to evaluate the feasibility of cell lines to be further developed into xenograft cancer models for small-animal PET imaging.

In vitro evaluation of fibrin mat and Tegaderm wound dressing for the delivery of keratinocytes--implications of their use to treat burns.

The effectiveness of fibrin mat and Tegaderm delivery systems to maintain clonogenic keratinocytes in culture were evaluated using in vitro methods. A fibrin mat was found to provide a culture environment that is conducive for the proliferation of keratinocytes and supporting their ability to form colonies of good growth potential in vitro. This confirms that the fibrin mat is a good delivery system for cultured epithelial autograft (CEA). In our unit, fibrin-CEA is limited only for the treatment of severe burns due to the high cost of fibrin glue. However, this substrate is able to maintain the regenerative properties of the CEA which is crucial for the treatment of extensive and full thickness burns. Tegaderm, a cost-effective polyurethane wound dressing is able to support keratinocyte cell growth but at a slower rate and with fewer colonies formed compared to the fibrin system. This suggests that Tegaderm can be an alternative approach of delivering autologous cells, limited to treat chronic wounds and less extensive burns. The use of simple and relatively inexpensive bench techniques can potentially serve as a quality control to check for keratinocytes cultured and delivered to every patient in the clinical setting.

Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies.

In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18-68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5 mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15-0.84, P=0.019) compared to low-dose ATG (<4.5 mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5 mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.

3T 1H-MR spectroscopy in grading of cerebral gliomas: comparison of short and intermediate echo time sequences.

BACKGROUND AND PURPOSE: Echo time (TE) can have a large influence on the spectra in proton MR spectroscopy ((1)H-MR spectroscopy). The purpose of this study was to comparatively assess the diagnostic value of 3T single-voxel (1)H-MR spectroscopy with short or intermediate TEs in grading cerebral gliomas. METHODS: Single voxel (1)H-MR spectroscopy was performed at 3T in 35 patients with cerebral glioma. The spectra were obtained with both short (35 ms) and intermediate TEs (144 ms). Metabolite ratios of choline (Cho)/creatine (Cr), Cho/N-acetylaspartate (NAA), lipid and lactate (LL)/Cr and myo-inositol (mIns)/Cr were calculated and compared between short and intermediate TEs in each grade. After receiver operating characteristic curve analysis, diagnostic accuracy for each TE in differentiating high-grade glioma from low-grade glioma was compared. RESULTS: At short TE, Cho/Cr and Cho/NAA ratios were significantly lower, and LL/Cr and mIns/Cr were significantly higher, compared with those at intermediate TE, regardless of tumor grade. Lactate inversion at intermediate TE was found in only 2 patients. At both TEs, there were significant differences in Cho/Cr and LL/Cr ratios between low- and high-grade gliomas. Diagnostic accuracy was slightly higher at short TE alone or combined with intermediate TE than intermediate TE alone (85.7% versus 82.9%). CONCLUSION: Metabolite ratios were significantly different between short and intermediate TE. Cho/Cr and LL/Cr ratios at either TE were similarly useful in differentiating high-grade gliomas from low-grade gliomas. If only a single spectroscopic sequence can be acquired, short TE seems preferable because of poor lactate inversion at intermediate TE on 3T single-voxel (1)H-MR spectroscopy.

Reversed discrepancy between CT and diffusion-weighted MR imaging in acute ischemic stroke.

PURPOSE: We sought to determine whether an early CT ischemic lesion showing parenchymal hypoattenuation might be undetectable on diffusion-weighted imaging (DWI) in acute cerebral ischemia. MATERIALS AND METHODS: We retrospectively evaluated CT and MR images of 70 consecutive patients with acute middle cerebral artery (MCA) infarction. All patients underwent CT and MR imaging within 6 hours of symptom onset. We determined the presence of reversed discrepancy (RD), defined as an early ischemic lesion showing parenchymal hypoattenuation on CT but no hyperintensity on DWI. CT Hounsfield units (HU), apparent diffusion coefficients (ADCs), and perfusion parameters were calculated for RD lesions. RESULTS: RD was found in 9 (12.9%) patients and at basal ganglia (89%). The mean HU of RD lesion was lower than that of normal tissue (DeltaHU, 2.33 +/- 0.74, P < .001). RD lesions showed no significant decrease of ADC (ADC ratio, 0.97 +/- 0.07, P = .059) and cerebral blood flow (relative CBF, 0.87 +/- 0.20, P > 0.05). Delayed DWI hyperintensity occurred in 8 (88.8%) RD lesions, and all lesions progressed to infarction. In 6 (66%) of 9 patients with RD, Alberto Stroke Program Early CT scores of ischemic lesions were lower on CT than those on DWI. CONCLUSION: RD was uncommonly found mainly in basal ganglia, and all RD lesions progressed to infarction at follow-up. Early CT ischemic lesion showing parenchymal hypoattenuation may be undetectable on DWI, and DWI may underestimate extent of severe ischemic tissue in patients with acute MCA infarction.

In vivo single-voxel proton MR spectroscopy in intracranial cystic masses.

PURPOSE: Our objective was to evaluate the proton MR spectroscopic pattern of the cystic contents of various intracranial masses and to report characteristic spectral patterns that may be helpful in the differential diagnosis of these lesions. METHODS: We evaluated 40 proton MR spectra obtained from cystic contents of various intracranial cystic masses in 39 patients, including gliomas (n = 14), metastases (n = 3), abscesses (n = 8), cysticercosis (n = 4), epidermoids (n = 3), and others (n = 7). Proton MR spectroscopy was performed on a 1.5-T MR unit using a point-resolved spectroscopic sequence with a 2 x 2 x 2 cm3 volume of interest. Assignment of the resonance peaks was based on previous studies. RESULTS: Adequate proton MR spectroscopic data were obtained in 35 cases (88%). In most gliomas and metastases, only a lactate resonance was observed. There was a trend toward a higher lactate peak in high-grade gliomas. A few tumors, including malignant gliomas and metastases, showed lipid signal combined with lactate signal. In abscesses, there were various combinations of lactate, acetate, succinate, amino acids (including valine, alanine, and/or leucine), and/or unassigned resonances. In cysticercosis, resonances of lactate, succinate, alanine, acetate, and/or unassigned resonances were observed. Three epidermoid cysts showed only lactate signal. There were no identifiable resonances from the arachnoid and porencephalic cysts. CONCLUSION: Only lactate is commonly observed in a variety of intracranial cystic masses, except for abscess and cysticercosis, in which resonances of acetate, succinate, amino acids, and/or unassigned metabolites can be seen in addition to a lactate peak.

Lateralizing ability of single-voxel proton mr spectroscopy in hippocampal sclerosis: comparison with mr imaging and positron emission tomography.

BACKGROUND AND PURPOSE: Proton MR spectroscopy (MRS) is still in the early stages in the evaluation of epilepsy, and comparisons with MR imaging and positron emission tomography (PET) in the same patients have rarely been documented. The purpose of this study was to evaluate the lateralizing ability of single-voxel MRS in comparison with MR imaging and PET in patients with hippocampal sclerosis. METHODS: Thirty-three patients with intractable temporal lobe epilepsy whose MR imaging diagnosis was unilateral hippocampal sclerosis and who underwent anterior temporal lobectomy and had good postsurgical outcome over 1-year follow-up were included in the study. MR spectra were obtained from the hippocampus bilaterally, using the point-resolved spectroscopy sequence. Metabolite ratios of NAA/Cho and NAA/Cr were calculated from the relative peak height measurements. An NAA/Cho ratio of 0.8 or less and an NAA/Cr ratio of 1.0 or less were regarded as abnormal. The MRS results were compared retrospectively with those of MR imaging and PET as to the ability to lateralize the epileptogenic focus. RESULTS: The sensitivity of MRS and PET (concordance with MR imaging) was 85% each in the lateralization of the ipsilateral lesion side. Bilateral abnormalities were seen in 30% of the patients. False-lateralization rates for MRS and PET were 3% and 6%, respectively. The concordance rate of MRS and PET was 73%, when comparing the results of the ipsilateral lesion side. CONCLUSION: MRS may be used as an adjunct tool in the evaluation of hippocampal sclerosis, like PET, although its sensitivity has to be improved and the clinical significance of bilateral abnormality is still to be determined.

Diffusion-weighted imaging in Wallerian degeneration.

We report two patients displaying hyperintensities on diffusion-weighted imaging (DWI) in the area of Wallerian degeneration (WD) at 12 days after stroke. High signal intensities were more conspicuous on DWI than on T2-weighted images. Both patients showed decreased diffusion anisotropy resulting in elevated apparent diffusion coefficient in the area of WD. These patients illustrate that DWI may be useful in the detection of the early stage of WD.

Effects of central application of naloxone on the skin temperature response in morphine-dependent rats.

This study was designed to identify if the surge in tail skin temperature (TST) observed following systemic administration of naloxone to morphine-dependent rats is mediated by a specific brain locus. Female rats were fitted with cannula located either in the preoptic area-anterior hypothalamus, locus coeruleus, or the frontal cortex. TST was monitored every 5 min for 60 min following central administration of naloxone (1-40 micrograms/0.4 microliters), in morphine-dependent rats. Regardless of the central site of naloxone injection, TST was significantly increased 4-5 degrees C. A threshold dose of 20 micrograms/0.4 microliters (10 micrograms/0.2 microliters, bilaterally) of naloxone was identified to produce this surge in TST in all three brain regions. These results suggest that morphine dependency sensitizes several brain regions to administration of naloxone such that the narcotic antagonist produces a similar change in TST as is observed following its systemic administration. These data further support the use of our morphine-dependent rat model to study the central mechanisms of the menopausal hot flush, and provide additional evidence that the flush response is centrally mediated.

In vivo proton magnetic resonance spectroscopy of central neurocytomas.

OBJECTIVE: The authors report on the metabolic features of central neurocytomas observed during in vivo single-voxel proton magnetic resonance spectroscopy. METHODS: Volume-selective single-voxel proton magnetic resonance spectroscopy was performed with a 1.5-T unit using a point-resolved spectroscopy sequence (TR/TE = 2000 ms/135 and 270 ms) to obtain spectra of a single 8-cc voxel. The subjects were five patients in the Department of Neurosurgery of Seoul National University Hospital whose central neurocytomas had been diagnosed histologically. The peak intensities of compounds containing choline (Cho), N-acetylaspartate, creatine/phosphocreatine, and lactate were analyzed. RESULTS: The ratios of Cho to creatine/phosphocreatine and Cho to N-acetylaspartate were significantly higher than ratios in normal brains. A lactate signal was present, and an unidentified signal was also observed at 3.55 ppm, which might have been produced by inositol or glycine. CONCLUSION: A combination of the signal at 3.55 ppm and a prominent Cho peak seems to be a characteristic feature of central neurocytomas. Volume-selective single-voxel proton magnetic resonance spectroscopy could provide additional information to aid in diagnosing this condition.

Similarities between morphine withdrawal in the rat and the menopausal hot flush.

Skin temperature, cardiovascular and neuroendocrine responses to morphine withdrawal in the rat were evaluated in an effort to develop a potential animal model for the menopausal hot flush in women. Morphine dependency was produced by s.c. implantation of pellets containing morphine alkaloid. In response to precipitous, naloxone-induced withdrawal, rats showed surges in tail skin temperature (TST) which were similar in magnitude (4.8 to 7.2 degrees C) and duration (60 to 90 min.) to peripheral skin temperature increases reported during menopausal hot flushes. Additionally, a brief period of accelerated heart rate (59%) and a 9-fold hypersecretion of luteinizing hormone (LH) preceded the TST response to morphine withdrawal. These cardiovascular and neuroendocrine responses are observed to precede or coincide with the menopausal hot flush. Additionally, protracted morphine withdrawal subsequent to abstention, resulted in TST instability characterized by spontaneous, high amplitude TST fluctuations. Thus, the alteration in skin temperature, heart rate and LH secretion during precipitated morphine withdrawal in the rat are similar in magnitude, duration and in their temporal relationship to those observed during the hot flush. These data suggest a possible opioid etiology in this vasomotor disturbance. Acute withdrawal in the morphine addicted rats may serve as an animal model by which to study the neural mechanism underlying the menopausal hot flush.

Diffusion-weighted MR imaging in biopsy-proven Creutzfeldt-Jakob disease.

OBJECTIVE: To compare conventional and diffusion-weighted MR imaging in terms of their depiction of the abnormalities occurring in Creutzfeldt-Jakob disease. MATERIALS AND METHODS: We retrospectively analyzed the findings of conventional (T2-weighted and fluid-attenuated inversion recovery) and diffusion-weighted MR imaging in four patients with biopsy-proven Creutzfeldt-Jakob disease. The signal intensity of the lesion was classified by visual assessment as markedly high, slightly high, or isointense, relative to normal brain parenchyma. RESULTS: Both conventional and diffusion-weighted MR images demonstrated bilateral high signal intensity in the basal ganglia in all four patients. Cortical lesions were observed on diffusion-weighted MR images in all four, and on fluid-attenuated inversion recovery MR images in one, but in no patient on T2-weighted images. Conventional MR images showed slightly high signal intensity in all lesions, while diffusion-weighted images showed markedly high signal intensity in most. CONCLUSION: Diffusion-weighted MR imaging is more sensitive than its conventional counterpart in the depiction of Creutzfeldt-Jakob disease, and permits better detection of the lesion in both the cerebral cortices and basal ganglia.

Usefulness of single voxel proton MR spectroscopy in the evaluation of hippocampal sclerosis.

OBJECTIVE: The purpose of our study was to determine the ability of H-1 MR spectroscopy (MRS) to lateralize the lesion in patients with hippocampal sclerosis. MATERIALS AND METHODS: Twenty healthy volunteers and 25 patients with intractable temporal lobe epilepsy whose MR imaging diagnosis was unilateral hippocampal sclerosis were included. This diagnosis was based on the presence of unilateral atrophy and/or high T2 signal intensity of the hippocampus. Singlevoxel H-1 MRS was carried out on a 1.5-T unit using PRESS sequence (TE, 136 msec). Spectra were obtained from hippocampal areas bilaterally with volumes of interest (VOIs) of 6.0 cm(3) and 2.25 cm(3) in healthy volunteers, and of either 6.0 cm(3) (n = 14) or 2.25 cm(3) (n = 11) in patients. Metabolite ratios of NAA/Cho and NAA/Cr were calculated from relative peak height measurements. The capability of MRS to lateralize the lesion and to detect bilateral abnormalities was compared with MR imaging diagnosis as a standard of reference. RESULTS: In healthy volunteers, NAA/Cho and NAA/Cr ratios were greater than 0.8 and 1.0, respectively. In patients, the mean values of these ratios were significantly lower on the lesion side than on the contralateral side, and lower than those of healthy volunteers (p <.05). The overall correct lateralization rate of MRS was 72% (18/25); this rate was lower with a VOI of 6.0 cm(3) than of 2.25 cm(3) (64% versus 82%, p <.05). Bilateral abnormalities on MRS were found in 24% (6/25) of cases. CONCLUSION: Although its rate of correct lateralization is low, single-voxel H-1 MRS is a useful and promising diagnostic tool in the evaluation of hippocampal sclerosis, particularly for the detection of bilateral abnormalities. To improve the diagnostic accuracy of H-1 MRS, further investigation, including the use of a smaller VOI and measurement of the absolute amount of metabolites, are needed.

Management of squamous cell carcinoma in a patient with dominant-type epidermolysis bullosa dystrophica: a surgical challenge.

Epidermolysis bullosa dystrophica is a rare congenital skin disease inherited either as a recessive or dominant form, the latter form being less common and much less severe. Squamous cell carcinoma is a rare complication in the dominant form of the disease, only three such cases being reported before, making this case the fourth known case. Although the squamous cell carcinoma is well-differentiated by histopathology, it has a poor prognosis owing to its invasiveness, distant metastases, and multicentricity. Its management also poses a great challenge to the surgeon and personnel involved in patient care. A complete outline of the total management of such a case is described with some interesting observations not mentioned previously in the literature. All the previous three patients are deceased, and this is the only known surviving patient.

Primary cutaneous cryptococcosis as the presenting manifestation of AIDS.

Presented is a case of primary cutaneous cryptococcosis, presenting as a papular facial lesion with subsequent ulceration, as the initial manifestation of AIDS. This unusual condition must be considered in the workup of unexplained or therapeutically unresponsive skin lesions. If it is diagnosed in an ostensibly "healthy" individual, evaluation for evidence of immunosuppression, and its underlying cause, must be undertaken.

Ultasonic debridement: a new approach in the treatment of burn wounds.

In an experimental group of 40 rats, the ultrasonic cleaner proved safe and effective in reducing the bacterial count of infected full-thickness burn wounds, with a markedly improved mortality rate and degree of healing.

Carotid-cavernous sinus fistula occurring after a rhinoplasty. Case report.

We report a case of carotid-cavernous sinus fistula which developed after elective nasal surgery. As the carotid-cavernous sinus fistula is a rare but major complication of craniofacial injury, surgeons who operate in this area should by aware of the entity.

Familial subungual keratoacanthoma in association with ectodermal dysplasia.

Described is the first report of familial SUKA, occurring in two of three sisters with ectodermal dysplasia, a rare, hereditary disorder involving ectodermally derived organ systems. Although rare, SUKA should be considered when assessing rapidly growing nailbed lesions. Differentiation from subungual squamous cell carcinoma is essential. Tumor excision and curettage and close postoperative follow-up are recommended, with conservative amputation reserved for tumor recurrences. If the diagnosis of SUKA is confirmed in a female, an association with ectodermal dysplasia should be sought.

Simplified anatomic method of double-eyelid operation: septodermal fixation technique.

Conventionally, it has been argued that the aponeurosis meets the orbital septum below the upper tarsal border in Orientals. However, we have shown that the aponeurosis fused with the orbital septum above the upper tarsal border in 502 patients, which contradicts the classic concept. In 457 patients there were distinct layers of fascia anterior to the orbital septum that originate from the septum and insert onto the pretarsal aponeurotic expansion. In Oriental eyelids, the preaponeurotic fat and orbital septum hang below the fusion line of the septum and aponeurosis. The hanging portion of the septum was dissected from the aponeurosis, plicated, and sutured to the dermis of the pretarsal flap. We performed the septodermal fixation technique in 512 patients over 3 years starting in March of 1992. Complications and changes of the folds were analyzed. The technique produced much less edema and discomfort and created more natural fold lines than any other technique. Patients were very lightly satisfied with the shape of the folds that we were able to design and adjust precisely with this method.