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Biomedical subjects

J H Suh

Publications and source records attributed to J H Suh.

At least 19 recordsLinked to original sources

Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases.

Efaproxiral (Efaproxyn, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O(2)) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to efaproxiral exposure (efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction x 10 days), plus supplemental O(2) (4 l/min), either with efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (> or =483 microg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients. This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements.

Aniline Compounds↗

Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress.

alpha-Lipoic acid (LA), a naturally occurring dithiol compound, has long been known as an essential cofactor for mitochondrial bioenergetic enzymes. Aside from its enzymatic role, in vitro and in vivo studies suggest that LA also acts as a powerful micronutrient with diverse pharmacologic and antioxidant properties. Pharmacologically, LA improves glycemic control, polyneuropathies associated with diabetes mellitus, and effectively mitigates toxicities associated with heavy metal poisoning. As an antioxidant, LA directly terminates free radicals, chelates transition metal ions (e.g. iron and copper), increases cytosolic glutathione and vitamin C levels and prevents toxicities associated with their loss. These diverse actions suggest that LA acts by multiple mechanisms both physiologically and pharmacologically, many of which are only now being explored. Herein, we review the known biochemical properties of LA with particular reference to how LA may be an effective agent to ameliorate certain pathophysiologies of many chronic diseases.

Animals↗

The effects of dual blockade of the renin-angiotensin system on urinary protein and transforming growth factor-beta excretion in 2 groups of patients with IgA and diabetic nephropathy.

AIMS: The therapeutic benefits of dual blockade of the renin-angiotensin system (RAS) have been inconsistent on renal function and proteinuria. To know the contribution of the heterogeneity of study subjects to such inconsistency, we evaluated the effects of dual blockade of RAS in 2 groups of selected renal diseases, IgA and diabetic nephropathy. To avoid confounding by the blood pressure-reducing effects, angiotensin II receptor antagonists (ATRAs) were added on the patients with long-term, optimally controlled blood pressure taking ACE inhibitors. Twenty-four-hour urinary protein excretion rate and urinary TGF-beta1 level were measured as surrogate markers of renal injury. METHODS: We conducted a prospective crossover trial with 14 IgA and 18 type-2-diabetic nephropathy patients showing moderate degree of proteinuria (> or = 1.0 g/day) and renal dysfunction (creatinine clearance 25 - 75/ml/min). Four to 8 mg once-daily dose of candesartan and placebo were alternatively added on ramipril dose of 5 - 7.5 mg/day for 16 weeks. RESULTS: All baseline data except for the age factor were statistically the same between the 2 disease groups. Twenty-four-hour mean arterial blood pressures were 91.2 +/- 1.6 and 92.3 +/- 1.8 mmHg in IgA and diabetic nephropathy patients respectively at baseline (p = NS). Mean arterial pressure did not change by the addition of candesartan or placebo in both groups. The addition of candesartan (combination) reduced 24-hour urinary protein excretion rate in IgA nephropathy patients with a mean change of -12.3 +/- 4.5%, which is significantly greater compared to a mean change of -0.1 +/- 3.3% after the addition of placebo (placebo) (mean difference 12.4 +/- 5.0, 95% CI 1.2 - 23.5; p < 0.05). Urinary TGF-beta1 level was reduced considerably by the combination therapy, with a -28.9 +/- 6.0% decrease, which was significantly different to that by the placebo, with +4.3 +/- 12.4% (33.3 +/- 13.5, 3.2 - 63.3; p < 0.05). In diabetic nephropathy patients, the addition of candesartan did not reduce 24-hour urinary protein excretion rate. Mean changes of 24-hour urinary protein excretion rate were -0.8 +/- 4.7% by the combination therapy and +0.5 +/- 6.1% by placebo (mean difference 1.3 +/- 4.7, 95% CI -6.8 - 13.5; p < NS). The level of urinary TGF-beta1 was reduced by the combination therapy, with -14.3 +/- 9.5% decrease, but it did not reach statistical significance compared to placebo of +0.7 +/- 15.5% (15.0 +/- 13.5, -14.4 - 44.5; p < NS). The changes in 24-hour urinary protein excretion rate and urinary TGF-beta1 level were neither correlated with each other, nor with the change in mean arterial pressure. Significant changes in the renal function were not detected during the study period. CONCLUSION: Definite beneficial effects of dual blockade of RAS on proteinuria and TGF-beta1 excretion were found in IgA nephropathy patients, which was independent of blood pressure-reducing effect. With our 16-week trial, such benefits were not observed in type 2 diabetic nephropathy. The reduction in urinary TGF-beta1 level suggests that the combination therapy may provide additional renoprotection through the antisclerosing effects. Based on our results, for a proper interpretation the therapeutic effects of the combination therapy should be evaluated separately according to the underlying renal disease.

Adult↗

Radiosurgery for patients with brain metastases: a multi-institutional analysis, stratified by the RTOG recursive partitioning analysis method.

PURPOSE: To estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class and treated with radiosurgery (RS) plus whole brain radiotherapy (WBRT). METHODS AND MATERIALS: An analysis of the RS databases of 10 institutions identified patients with brain metastates treated with RS and WBRT. Patients were stratified into 1 of 3 RPA classes. Survival was evaluated using Kaplan-Meier estimates and proportional hazard regression analysis. A comparison of survival by class was carried out with the RTOG results in similar patients receiving WBRT alone. RESULTS: Five hundred two patients were eligible (261 men and 241 women, median age 59 years, range 26-83). The overall median survival was 10.7 months. A higher Karnofsky performance status (p = 0.0001), a controlled primary (median survival = 11.6 vs. 8.8 months, p = 0.0023), absence of extracranial metastases (median survival 13.4 vs. 9.1 months, p = 0.0001), and lower RPA class (median survival 16.1 months for class I vs. 10.3 months for class II vs. 8.7 months for class III, p = 0.000007) predicted for improved survival. Gender, age, primary site, radiosurgery technique, and institution were not prognostic. The addition of RS boosted results in median survival (16.1, 10.3, and 8.7 months for classes I, II, and III, respectively) compared with the median survival (7.1, 4.2, and 2.3 months, p <0.05) observed in the RTOG RPA analysis for patients treated with WBRT alone. CONCLUSION: In the absence of randomized data, these results suggest that RS may improve survival in patients with BM. The improvement in survival does not appear to be restricted by class for well-selected patients.

Adult↗

The sensitivity and specificity of FDG PET in distinguishing recurrent brain tumor from radionecrosis in patients treated with stereotactic radiosurgery.

Radiation necrosis and recurrent brain tumor have similar symptoms and are indistinguishable on both magnetic resonance imaging (MRI) and computed tomograph scans. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been proposed as a diagnostic alternative, particularly when co-registered with MRI. We studied 47 patients with brain tumors treated with stereotactic radiosurgery and followed with FDG PET. For all tumor types, the sensitivity of FDG PET for diagnosing tumor was 75% and the specificity was 81%. For brain metastasis without MRI co-registration, FDG PET had a sensitivity of 65% and a specificity of 80%. For brain metastasis with MRI co-registration, FDG PET had a sensitivity of 86% and specificity of 80%. MRI co-registration appears to improve the sensitivity of FDG PET, making it a useful modality to distinguish between radiation necrosis and recurrent brain metastasis.

Adolescent↗

Tumor distribution and survival in six patients with brain metastases from cervical carcinoma.

OBJECTIVE: The aim of this study was to investigate the patterns of brain involvement and the outcome of patients with brain metastases from cervical carcinoma. METHODS: Between January 1982 and November 1999, 1279 patients with brain metastases were treated at the Cleveland Clinic. Six of them had brain metastases from cervical carcinoma. We retrospectively reviewed the patient and tumor characteristics at the time of the primary diagnosis as well as at the time of the brain metastases diagnosis. RESULTS: Brain metastases from cervical carcinoma were rarely accompanied by systemic disease, but they were commonly accompanied by uncontrolled local-regional disease. The median interval from the appearance of the primary carcinoma to the detection of brain metastases in 5 patients was 12 months. Multiple brain lesions developed in 4 of 6 patients and consisted of multiple tumors distributed in the cerebral hemispheres (2 patients) or both the cerebral and the cerebellar hemispheres (2 patients). Only 2 patients had a single lesion confined to a cerebral hemisphere. One patient was treated with stereotactic radiosurgery alone, 3 with surgery followed by whole brain radiation therapy, 1 with whole brain radiotherapy, and 1 each with whole brain radiotherapy and stereotactic radiosurgery. Patients treated with surgery had a median survival of 8.25 months, while patients treated with whole brain radiotherapy with or without stereotactic radiosurgery had a median survival of 3.75 months. The 1 patient treated with stereotactic radiosurgery alone survived for 22.5 months. CONCLUSION: Although the number of the patients was too small to detect definitive patterns of brain metastases from cervical carcinoma, the results of our review suggest that, in contrast to previous reports, extended survival can occur with more aggressive treatment such as surgery or stereotactic radiosurgery.

Adult↗

The effect of radiation therapy on brain metastases from endometrial carcinoma: a retrospective study.

OBJECTIVE: The objective of this study was to investigate the effectiveness of radiation therapy as a treatment for brain metastases from endometrial carcinoma. METHODS: Between July 1985 and November 1999, 10 patients with brain metastases from endometrial carcinoma were treated at the Cleveland Clinic. We reviewed the patient and tumor characteristics at the time of the primary diagnosis and the brain metastases diagnosis. For the 8 patients who received radiation therapy with or without surgery, we analyzed the treatment results with regard to survival and local control of the metastases. RESULTS: Brain metastases from endometrial carcinoma were commonly accompanied by uncontrolled local-regional disease and systemic metastases. Multiple brain lesions developed in 7 of 10 patients. Two patients were treated with surgery alone and had a median survival of 2.75 months (4 and 1.5 months) after the brain metastases diagnosis. Three patients were treated with surgery and radiation therapy and lived for a median survival of 15 months (range 11.5 to 15.5 months). The 5 patients who were treated with radiation therapy without surgery had a median survival of 2.4 months (range 0.25 to 6 months). Patients with multiple brain metastases had a shorter survival than patients with a single metastasis. CONCLUSION: Overall survival after brain metastases development in patients with endometrial carcinoma was poor. Although the number of patients was small, radiation therapy alone resulted in poor survival. Combination treatment with surgery and radiation therapy may improve survival for selected patients.

Adenocarcinoma↗

Inhibition effect of initial Pb2+ concentration on Pb2+ accumulation by Saccharomyces cerevisiae and Aureobasidium pullulans.

Pb2+ accumulation by Saccharomyces cerevisiae and Aureobasidium pullulans was inhibited by the initial Pb2+ concentration. In the case of S. cerevisiae, as initial Pb2+ concentrations increased, the accumulated Pb2+ per unit cell dry weight at equilibrium and the time required to reach an equilibrium state increased at low initial Pb2+ concentration. On the contrary, the accumulated Pb2+ decreased at high initial Pb2+ concentration at all pH values. The inhibition effect of initial Pb2+ concentration was delayed by the decrease of pH. However, the maximal Pb2+ accumulation capacity of S. cerevisiae was almost constant regardless of pH values. In the case of A. pullulans, the time required to reach an equilibrium state was independent of the initial Pb2+ concentration. The maximal Pb2+ accumulation capacity of A. pullulans decreased according to the decrease of pH values. However, the initial Pb2+ concentration needed to reach maximal Pb2+ accumulation amount was almost constant.

Adsorption↗

Covered retrievable tracheobronchial hinged stent: an experimental study in dogs.

PURPOSE: To evaluate the safety and technical feasibility of the use of a covered retrievable tracheobronchial hinged stent and investigate the histopathologic airway changes after placement and removal of the stent in dogs. MATERIALS AND METHODS: The experimental stent was composed of tracheal and bronchial stents that were connected together at their ends. Each stent was woven from a single thread of 0.2-mm-diameter nitinol wire filament in a tubular configuration and covered with polyurethane solution by a dipping method. Drawstrings were attached at the upper end of the tracheal stent for stent removal. Under fluoroscopic guidance, 20 stents were placed at the lower trachea and left main bronchus in 20 dogs and were electively removed 4 weeks (n = 10) or 8 weeks (n = 10) after placement. Ten dogs were killed just after stent removal and the remaining 10 were killed 2 weeks after stent removal. RESULT: Stents were successfully placed in all dogs. Pneumonia was observed in three dogs. Stent migration occurred in seven dogs (35%). Except for two cases of stent expectoration, 18 stents were easily removed within a few minutes. There was considerable granulation tissue proliferation and inflammatory reaction in the airways of the dogs that were killed just after stent removal. The pathologic changes of the airways returned to almost-normal conditions 2 weeks after stent removal. CONCLUSION: Placement and removal of a covered retrievable tracheobronchial hinged stent seems to be feasible, and histopathologic changes of the airway related to the stents returned to normal 2 weeks after stent removal.

Animals↗

Suppression of IL-8 gene expression by radicicol is mediated through the inhibition of ERK1/2 and p38 signaling and negative regulation of NF-kappaB and AP-1.

We show that radicicol, an anti-fungal agent, inhibits interleukin-8 (IL-8) production by the human monocyte line THP-1 in response to phorbol-12-myristate-13-acetate/lipopolysaccharide (PMA/LPS). IL-8 is a potent chemokine and needs for an optimal immune response--such as inflammation by activation of neutrophils. The decrease in PMA/LPS-induced IL-8 mRNA expression was demonstrated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Since the promoter in IL-8 gene contains binding motifs for NF-KB, AP-1. and NF-IL6, which appear to be important in IL-8 induction, the effects of radicicol on the activation of these transcription factors were examined. Treatment of radicicol to THP-1 cells produced a strong inhibition of NF-KB and AP-1, while NF-IL6 was not significantly affected by radicicol. Western blot analysis showed that radicicol inhibited the phosphorylation and phosphotransferase activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38. PD98059 and SB203580, known as a specific inhibitor of MEKI and p38 kinase, respectively, inhibited IL-8 gene expression showing that both of the kinase pathways are involved in IL-8 regulation in human monocytes. Collectively, this series of experiments indicates that radicicol inhibits IL-8 gene expression by blocking ERK1/2 and p38 signaling.

Blotting, Western↗

Metastatic seeding of the stereotactic biopsy tract in glioblastoma multiforme: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: The first case was recently reported of tumor seeding by glioblastoma multiforme (GBM) after stereotactic biopsy. This occurred despite radiosurgical treatment of the lesion post-biopsy. We report the first case of metastatic seeding along the needle biopsy tract of a GBM in which the tract was within the treatment field of subsequent fractionated radiation therapy. CLINICAL PRESENTATION: A 56-year-old man presented with left-sided focal motor seizures. An MRI showed an enhancing right cingulate gyrus lesion. INTERVENTION: A stereotactic biopsy of the lesion disclosed GBM. Radiation therapy was begun 25 days after biopsy and was completed 39 days thereafter. The biopsy tract received a minimum of 60 Gy. Subsequent magnetic resonance scanning showed the lesion to have doubled in size and evidence of enhancement along the biopsy tract. At surgery, specimens obtained from the biopsy tract, as determined using surgical navigation, revealed GBM. CONCLUSION: Seeding of the biopsy tract, radioresistance and the time interval until radiotherapy are the most likely explanations for tumor growth along the biopsy tract in this case. Consideration should be given for an early start to radiotherapy among those who undergo stereotactic biopsy for GBM. Further research will allow one to determine the radiosensitivity of these tumors and determine which patients may benefit from a radiosurgical or fractionated radiotherapy boost to the biopsy tract.

Antineoplastic Agents, Hormonal↗

Gamma knife radiosurgery in the management of patients with acromegaly: a review.

Although acromegaly is a rare disease, the need for an effective treatment that is able to induce biochemical cure is an extremely important issue. Unsuccessfully treated acromegaly is associated with increased morbidity and an age-corrected mortality so that early and aggressive therapy to normalize hormonal levels should be instituted at diagnosis. Ideally, the growth hormone-secreting adenoma should be completely resected, with preservation or subsequent restoration of pituitary function. Patients with recurrence or failure after surgery are treated with a second surgery, medical, radiation treatment, or combined modality treatment. Steotactic radiosurgery with gamma knife allows the delivery of focused radiation in a single session to the pituitary tumor that delivers a more biologically effective dose to the tumor than fractionated radiotherapy. Its use as a primary or adjuvant treatment for acromegalics may be more cost effective than medical treatment in these patients. Although it seems to be very effective in controlling growth and secretion of the growth hormone-secreting pituitary adenomas, there is a chance that some major risks from gamma knife radiosurgery might occur. This article will review the role that gamma knife radiosurgery might have in patients with acromegaly.

Acromegaly↗

Radiation prophylaxis for heterotopic ossification of the knee.

Heterotopic ossification (HO) occurs in 42% of patients who have undergone total knee arthroplasty. Bone formation usually is found in the quadriceps expansion and causes minimal to no symptoms. Specific therapy usually is unnecessary, but cases have been reported in which manipulation under anesthesia or revision arthroplasty has been required. We report a small series of 5 patients (6 knees) who have undergone surgical intervention for HO of the knee with radiotherapy given postoperatively for prophylaxis against future HO. Although this series is small, it appears that the use of prophylactic radiation may reduce recurrence after resection of symptomatic HO after total knee arthroplasty. Further investigation is required to confirm these preliminary findings.

Adult↗

Three cases of fistulae arising from gastrointestinal tract treated with endoscopic injection of Histoacryl.

Treatment of gastrointestinal fistula usually consists of conservative management and surgery as definite therapeutic measure. Histoacryl can be used to treat gastrointestinal fistula with no response to conservative management in surgically high-risk patients. We report here three cases of gastrointestinal fistula successfully treated with endoscopic injection of Histoacryl through a catheter into the internal opening and fistulous tract.

Enbucrilate↗

Identification of IgE-binding components of citrus red mite in sera of patients with citrus red mite-induced asthma.

BACKGROUND: Our previous investigations demonstrated that citrus red mite (CRM) antigen could cause IgE-mediated bronchoconstriction in exposed farmers working on citrus farms. OBJECTIVE: This study was performed to confirm IgE-binding components and major allergens within the CRM antigens. METHODS: Ten subjects who had been diagnosed as having CRM-induced asthma were enrolled. Serum-specific IgE antibodies to CRM antigens were measured by using an ELISA. To identify IgE-binding components and major allergens, SDS-PAGE, 2-dimensional PAGE, IgE-immunoblot analysis, and amino acid sequencing of major allergens were performed. RESULTS: All the asthmatic subjects had high specific IgE antibodies to CRMs. Twelve percent SDS-PAGE analysis showed more than 10 protein bands ranging from 6 to 64 kd. SDS-PAGE and IgE-immunoblot analysis with each individual serum showed 5 IgE-binding components (11, 24, 35, 40, and 64 kd), with 2 (24 and 35 kd) of them bound in more than 50% of the study subjects. Two-dimensional PAGE and IgE-immunoblot analysis demonstrated that the major allergen at 24 kd had 2 bands with different isoelectric points of 4.75 and 5.1. Thirty-five kilodaltons had one band with an isoelectric point of 4.75. All amino acid sequencing of the 2 major allergens was performed, which was not homologous with any previously characterized allergens. CONCLUSION: Five IgE-binding components and 2 major allergens (24 and 35 kd) were identified within the CRM antigen. The N-terminal amino acid sequence of the 2 major allergens (24 and 35 kd) was determined.

Adult↗

Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid.

Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. To determine the extent of age-related myocardial oxidative stress, oxidant production, antioxidant status, and oxidative DNA damage were measured in hearts of young (2 months) and old (28 months) male Fischer 344 rats. Cardiac myocytes isolated from old rats showed a nearly threefold increase in the rate of oxidant production compared to young rats, as measured by the rates of 2,7-dichlorofluorescin diacetate oxidation. Determination of myocardial antioxidant status revealed a significant twofold decline in the levels of ascorbic acid (P = 0.03), but not alpha-tocopherol. A significant age-related increase (P = 0.05) in steady-state levels of oxidative DNA damage was observed, as monitored by 8-oxo-2'-deoxyguanosine levels. To investigate whether dietary supplementation with (R)-alpha-lipoic acid (LA) was effective at reducing oxidative stress, young and old rats were fed an AIN-93M diet with or without 0.2% (w/w) LA for 2 wk before death. Cardiac myocytes from old, LA-supplemented rats exhibited a markedly lower rate of oxidant production that was no longer significantly different from that in cells from unsupplemented, young rats. Lipoic acid supplementation also restored myocardial ascorbic acid levels and reduced oxidative DNA damage. Our data indicate that the aging rat heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation.

Aging↗

Prospective study of hepatic, renal, and haematological surveillance in hazardous materials firefighters.

OBJECTIVES: To evaluate possible health effects related to work with hazardous materials as measured by end organ effect markers in a large cohort over about 2 years, and in a subcohort over 5 years. METHODS: Hepatic, renal, and haematological variables were analysed from 1996-98 in hazardous materials firefighters including 288 hazardous materials technicians (81%) and 68 support workers (19%). The same end organ effect markers in a subcohort of the technicians were also analysed (n=35) from 1993-98. Support workers were considered as controls because they are also firefighters, but had a low potential exposure to hazardous materials. RESULTS: During the study period, no serious injuries or exposures were reported. For the end organ effect markers studied, no significant differences were found between technicians and support workers at either year 1 or year 3. After adjustment for a change in laboratory, no significant longitudinal changes were found within groups for any of the markers except for creatinine which decreased for both technicians (p<0.001) and controls (p<0.01). CONCLUSIONS: Health effects related to work are infrequent among hazardous materials technicians. Haematological, hepatic, and renal testing is not required on an annual basis and has limited use in detecting health effects in hazardous materials technicians.

Adult↗

Viable myocardium in reperfused acute myocardial infarction: rest and stress first-pass mr imaging.

Feasibility of identifying viable myocardium in rest and stress magnetic resonance imaging (MRI) was evaluated using 3 hr occlusion and 30 min reperfusion model of left anterior descending (LAD) coronary artery in 12 felines. At rest MRI, viable myocardium confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC)-staining showed rapid signal intensity (SI) rise followed by gradual decline not significantly different from normal myocardium that the two hyperperfused regions were distinguishable only from the hypoperfused nonviable myocardium. At stress MRI, hyperemia induced perfusion change was most pronounced in normal myocardium with earlier and greater peak enhancement followed by brisk 'washout' phase while minimally augmented enhancement in viable myocardium was still in 'washin' phase. From these findings, it was concluded that viable myocardium is identified in rest and stress MRI as redistributing hypo- perfusion compared to persistent hyper-perfusion of the normal myocardium and the persistent hypo-perfusion of the nonviable myocardium.

Animals↗