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Biomedical subjects

K L Li

Publications and source records attributed to K L Li.

At least 19 recordsLinked to original sources

Simultaneous mapping of blood volume and endothelial permeability surface area product in gliomas using iterative analysis of first-pass dynamic contrast enhanced MRI data.

We describe a novel method for the calculation of endothelial permeability surface area product from dynamic contrast enhanced MRI. The technique uses iterative estimation to automatically decompose tissue residue function into intravascular and extravascular components, which are subsequently used to generate tumour blood volume, which is equal to relative cerebral blood volume calculated from T(1) weighted images and corrected for contamination by contrast agent leakage (rCBV(T1)(corrected), and endothelial permeability (k(fp)) maps. The technique was assessed in patients with cerebral glioma (n=5) by examining the reproducibility of endothelial permeability and rCBV(T1)(corrected) between two separate examinations conducted with a 2-day interval. The technique produces maps of endothelial permeability that appear to be free of any contribution from intravascular contrast agent. Maps of rCBV(T1)(corrected) show close correlation with maps of blood volume calculated from independently acquired dynamic susceptibility weighted MRI examinations, with no evidence of residual permeability effects. The results were highly reproducible with strong intra-class correlation between the two examinations for mean values and for 97.5 percentiles of endothelial permeability and rCBV(T1)(corrected). The excellent reproducibility of this technique and the ability to calculate endothelial permeability and rCBV(T1)(corrected) values from rapidly acquired data sets offer considerable advantages over conventional approaches and support the use of this methodology for therapeutic monitoring or trials of novel therapeutic agents.

Aged↗

Reproducibility of quantitative dynamic contrast-enhanced MRI in newly presenting glioma.

We have investigated the reproducibility of dynamic contrast enhanced imaging techniques in nine patients with cerebral glioma. Patients were imaged twice with a 2 day interval between scans. Maps were produced of the time taken to achieve 90% enhancement (T90), the maximal intensity change per time interval ratio (MITR), the volume transfer coefficient between plasma and the extravascular extracellular space (K(trans)) and the extravascular extracellular contrast distribution volume, v(e). Measurements of K(trans) greater than 1.2 min(-1) were used to exclude pixels where first pass perfusion effects dominated the measurement. Measures of the test-retest coefficient of variation (CoV) and intraclass correlation coefficients were used to assess reproducibility for measurements from a volume of interest containing enhancing tissue from the whole tumour. MITR showed poor reproducibility (mean CoV 17.9%, 95% confidence limits for group comparisons 20.2%). T90 showed good reproducibility (mean CoV 7.1%, 95% confidence limits for group comparisons 5.2%). Calculated values of K(trans) and v(e) also showed good reproducibility (mean CoV 7.7% and 6.2% respectively, 95% confidence limits for group comparisons 6.2% and 4.8%, respectively). We conclude that the measurements of K(trans) and v(e) derived from pharmacokinetic analysis are sufficiently reproducible to support their use as a biological markers in therapeutic trials.

Aged↗

Breath-hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first-pass leakage profile model.

We have applied a novel pharmacokinetic model of the distribution of contrast media to dynamic contrast-enhanced MRI data from patients with hepatic neoplasms. The model uses data collected during the passage of a bolus of contrast medium and allows breath-hold image acquisition. The aims of the study were to investigate the feasibility of permeability mapping using the first pass technique and breath-hold acquisitions, and to examine the reproducibility of the technique and the effect of the liver's dual vascular supply on the assumptions of the model. Imaging was performed in 14 patients with hepatic neoplasms. Dynamic data clearly demonstrated differences in the timing and shape of the contrast medium concentration-time course curve in the systemic arterial and portal venous systems. Mapping of the arrival time (T(0)) of contrast medium allowed identification of tissue supplied by the hepatic arteries and portal vein. Hepatic tumours all showed typical hepatic arterial enhancement. Repeated measurements of endothelial permeability surface area product (k(fp)) and relative blood volume (rBV), performed in five patients, showed excellent reproducibility with variance ratios (V(r)) of 0.134 and 0.113, respectively. Measurement of enhancing tumour volume was also highly reproducible (V(r) = 0.096) and this was further improved by the use of T(0) maps to identify pixels supplied by the hepatic artery (V(r) = 0.026). Estimates of k(fp) and rBV in normal hepatic tissue supplied by the portal vein were highly inaccurate and these pixels were identified by use of the T(0) parameter and excluded from the analysis. In conclusion, dynamic MRI contrast enhancement combined with a pharmacokinetic model of the distribution of contrast media in the first pass allows us to produce highly reproducible parametric maps of k(fp) and rBV from hepatic tumours that are supplied by the hepatic arterial system using breath-hold acquisitions.

Adenocarcinoma↗

Reproducibility of T2* blood volume and vascular tortuosity maps in cerebral gliomas.

The development of anti-angiogenic therapies for tumors has led to a demand for imaging-based surrogate markers of the angiogenic process. The utility of such markers is highly dependent on their test-retest reproducibility. This paper presents a formal assessment of the reproducibility of measurements of relative blood volume (rBV), normalized rBV (rBVnorm), and vascular tortuosity as estimated by measurement of relative recirculation (rR). The study was conducted in 11 patients with glioma who were scanned on two occasions 36-56 hours apart. The observed reliability estimates were used to calculate 95% confidence limits for detection of differences between groups and for changes in individual cases. The results show that measurement of rBV or rBVnorm in consecutive studies is statistically capable of reliably detecting changes in excess of 15% in between group studies and 25% in individual patients. Measurement of vascular tortuosity using is less reproducible but is able to confidently identify changes in excess of 30% in group studies and 35% in individuals.

Blood Volume↗

[Treatment of hemangioma in oral and maxillofacial region with intralesional injection of pingyangmycin].

OBJECTIVE: To investigate the indication and long term treatment results of intralesional injection of Pingyangmycin for hemangiomas in oral and maxillofacial regions. METHODS: Between June 1986 and June 2000, 1040 patients with maxillofacial hemangiomas were treated by intralesional injection of Pingyangmycin PYM . There were 312 males and 712 females. The types of hemangiomas included capillary 436, cavernous 238, mixed 260, arterial venous malformation 8 and port wine stain 9 . The injection was performed in stages and multi sites, repeated after 14 to 21 days for 2 to 3 times as one course. RESULTS: All the patients were followed up for 1 to 14 years. The cure rates of capillary, mixed and cavernous hemangioma were 96.40%, 92.20% and 67.20%, respectively. No effect was found for arterial venous malformations. The best dose effect was attained in 1mg/cm(2). The best concentration of Pingyangmycin was 1mg/ml for capillary hemangioma and the concentration may be higher for cavernous hemangiomas. Fever occurred in 6.54% of the cases. Serious complications associated with Pingyangmycin injection, such as pulmonary fibrosis were not found. CONCLUSION: Intralesional injection of Pingyangmycin can be used as the therapy of choice for capillary, mixed and cavernous hemangiomas in oral and maxillofacial region. The advantages included a high cure rate, safety, short course, manipulation with ease and fewer side effects.

English Abstract↗

Abnormalities of the contrast re-circulation phase in cerebral tumors demonstrated using dynamic susceptibility contrast-enhanced imaging: a possible marker of vascular tortuosity.

Dynamic susceptibility contrast-enhanced magnetic resonance (MR) imaging in tumors is restricted by relaxivity effects, which may obscure any abnormality of first-pass kinetics in the re-circulation phase. The purposes of this study were a) to document the magnitude of relaxivity effects with a variety of commonly used MR susceptibility imaging techniques; and b) to determine whether the re-circulation phase of the first-pass curve in tumors differs from that in normal tissue. We have confirmed that residual relaxivity effects can be eliminated from dynamic susceptibility contrast-enhanced data by several techniques. Application of these methods to enhancing vascular tumors allows detection of abnormalities in the re-circulation phase, which would otherwise be obscured. These abnormalities are independent of relative cerebral blood volume (rCBV) and presumably represent deviations from the predicted gamma variat flow pattern seen in normal tissues. We believe that the parameter rR described here provides an indicator of the chaotic nature of neovascular angiogenesis, which may be of benefit in diagnosis and management.

Brain↗

Quantification of endothelial permeability, leakage space, and blood volume in brain tumors using combined T1 and T2* contrast-enhanced dynamic MR imaging.

This study describes a method for imaging brain tumors that combines T1-weighted (T1W) and T2*-weighted (T2*W) dynamic contrast-enhanced acquisitions. Several technical improvements have been made to produce high-quality three-dimensional mapping of endothelial permeability surface area product (k) and leakage space (vl), based on T1W data. Tumor blood volume maps are obtained from T2*W images with a complete removal of residual relaxivity effects. The method was employed in 15 patients with brain tumors (5 gliomas, 5 meningioma, and 5 acoustic schwannoma). Mean values of vl were significantly greater in acoustic schwannomas (53% +/- 9%) than in meningiomas (34% +/- 7%) or gliomas (22% +/- 4%). Mean values of vl in meningioma were significantly greater than those of gliomas. Mean values of rCBV correlated closely with k. There was also a positive correlation between k and vl for pixels with low k values. This relationship was weaker in areas of high k. The highest mean ratios of k to vl (k(ep)) were seen in two patients with glioblastoma, one patient with transitional cell meningioma, and one patient with angioblastic meningioma. Pixel-by-pixel comparison showed a strong correlation between rCBV and k in 11 of 15 patients. However, decoupling between pixel-wise rCBV and k was found in four patients who had lesions with moderate k and vl elevation but no increase of rCBV. Results from this study suggest that in assessing the angiogenic activities in brain tumors it is advisable to monitor simultaneously changes in tumor blood volume, vessel permeability, and leakage space of tumor neovasculature.

Adult↗

Improved 3D quantitative mapping of blood volume and endothelial permeability in brain tumors.

We describe a new method to allow simultaneous mapping of endothelial permeability and blood volume in intracranial lesions. The technique is based on a tumor leakage profile during the first pass (fp) of contrast bolus calculated from the time-dependent plasma-contrast concentration function (PCCF) in three-dimensional (3D) T1-weighted dynamic studies. The performance of the method has been evaluated by comparing results with those obtained from more conventional methods in patients with primary brain neoplasms. The new permeability maps (k(fp)) are visually compatible with those calculated using a conventional multicompartment model (k(tran)). Quantitatively, the new maps are free from overestimation of k(tran) due to first-pass effects. The new blood volume maps, which segment out the contamination of contrast leakage, agree closely with maps derived from susceptibility studies. The new method is fast, robust, and easy to perform. The method is suitable for use in clinical environments and is likely to be of benefit where longitudinal assessment of treatment response is required.

Brain Neoplasms↗

Altered heel-pad mechanical properties in patients with Type 2 diabetes mellitus.

AIMS: To compare the heel-pad mechanical properties in patients with Type 2 diabetes mellitus with forefoot ulceration, without forefoot ulceration and age-matched healthy subjects. METHODS: Heel-pad mechanical properties in 40 heels of 20 healthy subjects (group I) age-matched with the other groups, 42 heels of 21 diabetic patients without forefoot ulceration (group II), and 14 heels of 12 diabetic patients with active forefoot ulceration (group III) were assessed using a self-constructed loading-unloading device and a 10-MHz linear-array ultrasound transducer. RESULTS: There were no differences in the unloaded heel-pad thickness, compressibility index and elastic modulus between the three groups. When compared with group I subjects (mean +/- SD, 27.9 +/- 6.1%), a significant increase (P < 0.001) was found in both group II (36.1 +/- 8.7%) and group III patients (43.2 +/- 6.6%) for the energy dissipation ratio. This ratio was also significantly different (P = 0.003) between groups II and III. CONCLUSIONS: The higher impact energy dissipated in the heel-pad may put patients with Type 2 diabetes at higher risk for developing foot ulceration.

Adult↗

Parametric mapping of scaled fitting error in dynamic susceptibility contrast enhanced MR perfusion imaging.

The purpose of this study was to examine the benefits of routine generation of a parametric image of scaled curve fitting errors in the analysis of dynamic susceptibility contrast enhanced MR perfusion imaging. We describe the scaled fitting error (SFE), which reflects the magnitude of potential errors in the estimation of perfusion parameters from dynamic susceptibility contrast enhanced studies. The SFE is the root-mean-square error between the observed values in the time course of change of effective transverse relaxation rate (delta R2* (t)) in tissue and the theoretical values derived by gamma variate curve fitting, scaled with a simple function related to the area under the fitted gamma variate curve. The SFE was tested using Monte Carlo simulation and by observations in normal volunteers and patients. This demonstrated that the SFE was linearly related to uncertainties in calculation of the values of relative cerebral blood volume (rCBV) and relative mean transit time (rMTT). High spatial resolution SFE maps were obtained in all volunteers and patients. In normal brain, SFE was consistently higher in white matter than in grey matter. In 54/85 patients with neurodegenerative or vascular brain disease, SFE maps showed focal areas with high values owing to poor signal to noise ratio in delta R2*(t). Increased SFE was also found in 11/54 brain tumours owing to loss of conformance of delta R2*(t) to the gamma variate function. SFE mapping is simple to implement and the computational overhead is negligible. It is concluded that parametric maps of SFE allow visual and quantitative comparison of fitting errors with the theoretical gamma variate model between anatomical regions and provide a quality control device to rapidly assess the reliability of the associated rCBV and rMTT estimations.

Adult↗

Factors related to the survival of papillary and follicular thyroid carcinoma patients with distant metastases.

There is limited clinical information comparing presentations and results of treatment of papillary and follicular thyroid carcinoma patients with distant metastases. We retrospectively analyzed data of 1,257 thyroid cancer patients who received their treatment and follow-up at Chang Gung Memorial Hospital. We found 992 patients with papillary carcinoma and 205 patients with follicular thyroid carcinoma. Of these, 68 patients with papillary thyroid carcinoma (6.9%) had distant metastases at the time of diagnosis or during the follow-up period. Of the follicular thyroid carcinoma patients, 69 (33.7%) had distant metastases. Of the 68 patients with papillary carcinoma, only 33 were categorized as stage IV at the time of diagnosis. Nine of the patients were categorized as clinical stage I carcinoma, 10 as stage II, and 16 as stage III. Sixteen patients (23.5%) died during the study period, all but 2 of thyroid cancer. Twelve of the 68 patients were disease-free after treatment. Of the 69 patients with follicular thyroid carcinoma, 58 were categorized as stage IV at the time of diagnosis. Six of the patients were categorized as clinical stage I carcinoma, 2 as stage II, and 3 as stage III at the time of diagnosis; all of these patients deteriorated to stage IV during the follow-up period. Of the 42 patients with follicular thyroid carcinoma involving bone, 24 presented with bone metastases during the initial diagnosis. After treatment, 25 of 69 patients with follicular carcinoma died of follicular carcinoma. Only 3 patients were disease-free after the treatment. In patients with follicular carcinoma, only tumor size was an important prognostic factor. In this study, 8 patients categorized as clinical stages I to III at the time of operation had thyroglobulin (Tg) levels less than 5 ng/mL and developed distant metastases during the follow-up period. In conclusion, at diagnosis a large group of Asian patients with metastatic well-differentiated thyroid cancer was more likely to have follicular than papillary histology, and that, as expected, metastases from follicular cancer were present earlier and more frequently, were more likely to involve bone, were more likely to be associated with mortality, and were linked to tumor size but not gender. Also unlike some other reports, treatment producing a low Tg did not always produce a good outcome. More aggressive surgical procedures may be able to improve outcomes.

Adenocarcinoma, Follicular↗

[Effects of "qing kai ling" injection on experimental cerebral hematoma in rabbits].

OBJECTIVE: To observe the effect of "Qingkailing" (QKL) on cerebral hematoma. METHODS: The experimental cerebral hematoma models were produced by injecting autogenous clot in the rabbit. The influences of QKL on blood gas, brain index, contents of water, sodium, potassium, calcium, magnesium in brain tissues and changes of cerebrovascular permeability, histomorphology at the third day, seventh day, fourteenth day after cerebral hematoma were observed. RESULTS: In the pathological group brain index and contents of water, sodium, calcium of brain tissue, ventilation of lung were increased progressively, cerebrovascular permeability were raised obviously, especially in the side of hematoma (right brain). After the forming of cerebral hematoma cerebral edema was reduced, brain index, contents of water, sodium, calcium in brain tissue and cerebrovascular permeability, hyperventilation were all less than pathological group and close to the control group. CONCLUSION: QKL was advantageous in the treatment of encephal edema induced by experimental cerebral hematoma.

Animals↗

The effect of ketoprofen creams on periodontal disease in rhesus monkeys.

Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The biochemical data demonstrated early and significant suppression of GCF-LTB4 by both ketoprofen formulations at 1 month, which preceded the significant suppression of GCF-PGE2 at 2 and 3 months in the ligature model (p < 0.003) and at 2 to 6 months in the spontaneous model (p < 0.02). We conclude that ketoprofen at 1% level in suitable topical vehicles can effectively inhibit GCF-LTB4 and GCF-PGE2 and positively alter alveolar bone activity in the ligature-induced model of periodontitis in the monkey.

Administration, Topical↗

The effect of ketoconazole in pre-operative treatment in Cushing's syndrome: three cases report.

Ketoconazole is an orally active imidazole derivative that is an effective therapeutic drug in the treatment of mycotic infection. The development of gynecomastia in male patients treated with ketoconazole has led to investigation of its potent inhibitory effect on adrenal steroidogenesis. In this study, we present our preliminary experience using high dose ketoconazole, which was used safely as a palliative treatment in 3 patients with Cushing's syndrome prior to surgery. The 24-hour urinary free cortisol excretion was decreased by more than 52% in 1 to 2 days and fell to within normal limits of less than 120 micrograms by the 1st day, 2nd day or 15th day in these 3 patients. Cushing's syndrome was either adrenocorticotropin-dependent or -independent during treatment. In case 3, the plasma adrenocorticotropin level was unchanged during treatment in the first week, despite marked reductions in plasma and 24-hour urinary free cortisol levels. The most significant improvement of clinical symptoms was that the patients could sleep much more comfortably at night following the suppression of hypercortisolism by ketoconazole. Monitoring of liver function and addition of dexamethasone are recommended to prevent the possibility of reversible adverse effects such as severe hepatic injury and adrenal insufficiency or even crisis.

Adrenocorticotropic Hormone↗

Outcome of Graves' thyrotoxicosis after antithyroid drug treatment.

To investigate the outcome of Graves' thyrotoxicosis after antithyroid drug management, data from 81 patients, treated in Chang Gung Memorial Hospital at Taipei and Linkou from October 1981 to March 1990, were analyzed. The gender ratio of female to male was 59:22. The mean age of onset was 33.1 +/- 10.5(15-60) year-old. All the patients were treated with antithyroid drug (Thionamide group) for a duration of 11 to 63 months (mean +/- SD = 28.1 +/- 9.8 months). Forty of 81 patients (49.4%) were remained remission after up to 2 years of follow-up. Those patients relapse usually occurred within 2 years after discontinuation of treatment (34/41), and only one exceptional case relapsed after 3 years. Three conditions affected the relapse rate. Patients with larger goiter (grade II-III) and shorter duration of treatment (< 23 months) had a higher relapse rate than those-with smaller goiter (grade O-I) [29/46 vs. 12/35; chi 2 = 6.576, p = 0.010; p = 0.015 in stepwise logistic regression (LR)] and longer duration of treatment (> or = 23 months) (15/20 vs. 26/61; chi 2 = 6.316, p = 0.012; p = 0.020 in LR). Patients with higher pre-treated serum triiodothyronine (T3) level (T3 > or = 300 ng/dl) had a higher relapse rate than those with lower T3 level (T3 < 300 ng/dl) in univariate analysis (30/50 vs. 11/31, chi 2 = 4.601, p = 0.032), but no significant difference by LR (P = 0.094). Other clinical parameters including age, sex, past history, family history, thyroxine (T4) level, T3/T4 ratio, thyroid autoantibodies, staging of ophthalmopathy, responsiveness to thyrotropin-releasing hormone stimulation test at the end of treatment, and whether combined treatment with thyroxine had no significant difference between the relapse and remission groups. These data suggest: (a) patients with larger goiter (grade II-III had higher relapse rate; (b) most of the recurrent thyrotoxicosis patients relapsed within two years after drug withdrawal; (c) continuing treatment for more than twenty-three months produces better outcome; (d) patients with Graves' thyrotoxicosis should be followed up for at least three years after withdrawal of antithyroid drug.

Adolescent↗

Sequential liver and bone biochemical changes in hyperthyroidism: prospective controlled follow-up study.

OBJECTIVE: To reexamine the prevalence and sequential changes of liver and bone biochemical abnormalities in patients with hyperthyroidism. METHODS: A consecutive series of 95 patients with hyperthyroidism and 66 controls with euthyroid goiter seen during same period were studied. The patients were treated with propylthiouracil (PTU) 300 mg/day for 2 months, followed by 100-150 mg/day for 3 months and a subsequent maintenance dose of 100 mg/day. Serum aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin, ALP isoenzymes, and hepatitis markers were studied before therapy and at 2 and 5 months after PTU therapy was begun. RESULTS: Seventy-two [75.8%, confidence interval (CI) 67.2-84.4%] of the 95 patients had at least one biochemical abnormality. AST, ALT, ALP, GGT, and bilirubin were elevated in 27.4%, 36.8%, 64.2%, 16.8%, and 5.3%, respectively. Of the 34 patients with ALT elevation, 62% showed gradual normalization of ALT, whereas 38% (CI 21.9-54.5%) showed transient, asymptomatic, but significant (p < 0.025) further elevation of ALT during PTU therapy. Overt hepatitis developed in one patient. None of these changes was due to hepatitis A, B, C, or delta virus infection or autoimmune hepatitis. Changes of serum GGT parallel those of ALT. In contrast, serum ALP (primarily bone isoenzyme) rose significantly (p < 0.01) as T4 and T3 levels declined at 2 months after therapy. CONCLUSIONS: The results suggest that hyperthyroidism is often associated with abnormal biochemical tests, particularly ALP elevation, and thus may pose diagnostic confusion. The increase of bone isoenzyme accounts for the elevations in total ALP level before and during therapy. Serum ALT and GGT abnormalities usually subside during PTU therapy, but transient asymptomatic PTU hepatotoxicity occurs in one-third of the patients. Discontinuation of PTU is not required unless overt hepatitis develops.

Adolescent↗