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Biomedical subjects

J Wong

Publications and source records attributed to J Wong.

At least 397 records · Page 22Linked to original sources
PubMed1996

Exogenous endothelin-1 causes renal vasodilation in the fetal lamb.

PURPOSE: Endothelin-1 is known to be a potent vasoconstrictor. We investigated the effects and mechanisms of action of endothelin-1 and its receptors in regulating renal vascular tone in the fetal lamb. MATERIALS AND METHODS: We observed the in vivo effects of endothelin-1, an endothelin-b receptor agonist (4-alanine-endothelin-1), endothelin-a receptor antagonists (BQ-610 and BQ-123), and the inhibition of prostaglandin and nitric oxide synthesis on the response of the renal circulation to endothelin-1 in a chronic preparation in third trimester fetal lambs. RESULTS: After injection of 250 ng./kg. endothelin-1 into the descending aorta proximal to the renal arteries in 8 fetal animals, renal blood flow increased (4.4 +/- 0.7 ml. per minute per kg., p < 0.001 versus vehicle), as did mean arterial blood pressure (3.0 +/- 0.3 mm. Hg,p < 0.001 versus vehicle). Calculated renal vascular resistance decreased (-1.1 +/- 0.2 mm. Hg per minute per kg./ml., p < 0.001 versus vehicle). After injection of 1,725 ng./kg. 4-alanine-endothelin-1 in 5 animals renal blood flow increased (3.8 +/- 0.4 ml. per minute per kg., p < 0.05 versus vehicle) and mean arterial blood pressure was unchanged (1.6 +/- 1.7 mm. Hg). Calculated renal vascular resistance decreased (-0.8 +/- 0.2 mm. Hg per minute per kg./ml., p < 0.05 versus vehicle). After injection of 0.5 mg./kg. BQ-610 in 6 animals renal blood flow increased (2.3 +/- 0.7 ml. per minute per kg., p < 0.05) and mean arterial blood pressure decreased (-2.7 +/- 0.3 mm. Hg, p < 0.05 versus vehicle). Calculated renal vascular resistance decreased but this difference was not statistically significant (-0.7 +/- 0.3 mm. Hg per minute per kg./ml., p < 0.07). A dose of 1 mg./kg. BQ-123 in 2 animals decreased renal vascular resistance markedly. Infusion of a prostaglandin synthesis inhibitor (1 mg./kg. per minute meclofenamic acid) did not alter the decrease in renal vascular resistance after endothelin-1 (-0.7 +/- 0.4 mm. Hg per minute per kg./ml). In contrast, during infusion of a nitric oxide synthesis inhibitor (1.5 mg./kg. per minute N-omega-nitro-L-arginine) endothelin-1 increased renal vascular resistance (1.2 +/- 0.2 mm. Hg per minute per kg./ml., p < 0.001). CONCLUSIONS: Endothelin-1 is a vasodilator in the fetal renal circulation, which acts primarily via endothelin-b receptors. Ongoing activity of endothelin-a receptors contributes to renal vascular tone in fetal lambs. The vasodilatory effects of endothelin-1 in the fetal lamb renal circulation are mediated via the nitric oxide system and not via prostanoids.

Animals↗
PubMed1996

Does once-daily dosing of aminoglycosides affect neuromuscular function?

OBJECTIVE: Aminoglycosides have been reported to produce a curare-like neuromuscular blockade in animals at serum concentrations higher than those obtained with traditional dosing (1-2 mg/kg every 8 h) in humans. Aminoglycoside-induced neuromuscular blockade is rarely, if ever, seen in humans with traditional dosing. The recent adoption of once-daily dosing of aminoglycosides has raised concerns about increased potential for this adverse effect because higher serum concentrations are produced. The objective of this study was to determine if once-daily dosing of aminoglycosides inhibits respiratory muscle function. METHOD: Nine mechanically ventilated ICU patients on once-daily dosing of gentamicin 6 mg/kg/day were assessed for respiratory muscle strength by measuring maximum inspiratory pressure (MIP). MIP is a measurement of the maximal negative pressure generated by repeated inhalations against an occluded airway over 20 s. This was measured within 1 hour before (MIPpre) and within 1 hour after each aminoglycoside dose (MIPpost). RESULTS: Mean values for MIPpre and MIPpost were -26.7 cm H2O and -26.5 cm H2O, respectively. The mean difference between MIPpre and MIPpost was -0.2 cm H2O, which was not statistically significant (P > 0.05). CONCLUSION: The effect of gentamicin (6 mg/kg/day) on respiratory muscle function was not statistically, nor clinically significant, and weaning from mechanical ventilation does not seem to be inhibited by once-daily dosing of aminoglycosides as detectable by measurement of MIP.

Anti-Bacterial Agents↗
PubMed1996

Transcatheter embolization of coronary artery fistula with controlled release coils.

The treatment for large congenital coronary cameral fistulas has been surgical but with advances in interventional catheterization techniques transcatheter embolization of these fistulas with coils or detachable balloons is now possible. This report describes occlusion of a congenital coronary arteriovenous fistula in a 6-year-old girl.

Child↗
PubMed1996

Assessment of left ventricular function after radiofrequency and direct current atrioventricular node ablation.

BACKGROUND: There is limited information available regarding the effect of catheter ablation of the antioventricular (AV) junction on left ventricular (LV) function. Both deterioration and improvement in LV function have been reported following direct current (DC) ablation of the AV junction. The deterioration of LV function following DC ablation of the AV junction may be due to the accompanying barotrauma, DC arcing and direct coagulation, or even the effects of chronic ventricular pacing. If this deterioration of LV function was a result of the accompanying effects of DC shock, the use of radiofrequency ablation (RF) should not result in deterioration of LV function. AIM: To study LV function before and after different methods of AV junction ablation and in patients with chronic ventricular pacing without AV junction ablation. MATERIAL: This study assessed LV function in patients following RF ablation, low energy DC ablation of the AV junction and compared the results with our previously reported finding in patients who had AV junction ablation using high energy DC shock. A group of patients undergoing permanent single chamber ventricular pacemaker implantation without AV junction ablation were selected as controls. METHODS: All patients were paced in the ventricle at 110 beats/minute during LV function assessment by radionuclide angiography. Global LV function and segmental wall motion abnormalities were assessed before, immediately following and three months after ablation. RESULTS: In the high energy DC ablation group, a fall in global LV function (50 +/- 3.0% to 43 +/- 3.0%, p = 0.02) and impairment of segmental wall motion were detected. Low energy DC ablation resulted in segmental wall motion impairment similar to high energy DC but without affecting global ejection fraction (47.0% +/- 6.7 to 45.5% +/- 3.1, p > 0.05). Neither RF ablation (44.0% +/- 3.3 to 45.3% +/- 3.5, p > 0.05), nor chronic pacing (46.7% +/- 4.9 to 47.0% +/- 2.9 p > 0.05) had any effect on global or segmental LV function. CONCLUSIONS: Low energy DC or RF ablation of the AV junction does not affect global LV ejection fraction. The deterioration of global LV function after high energy DC shock ablation appears to be related to the accompanying effects of DC energy and not to the effects of chronic ventricular pacing.

Adult↗
PubMed1996

Use of flow cytometry in the analysis of stage III squamous cell carcinoma of the oesophagus and its association with MIB-1.

AIMS: To examine the prognostic and pathobiological importance of DNA content in oesophageal squamous cell carcinomas in Hong Kong Chinese subjects; to evaluate its association with the immunohistochemical proliferative marker MIB-1. METHODS: Paraffin wax embedded tumour tissue and adjacent normal tissue (control tissue) samples from 45 resected stage III oesophageal squamous cell carcinomas were studied using flow cytometric analysis. The DNA content and the clinicopathological data of these patients were analysed together with the MIB-1 labelling index. RESULTS: DNA aneuploidy was present in 14 (31%) of the 45 cases. However, the DNA content did not correlate significantly with the age, sex, or survival of the patients, nor the length, location, differentiation and MIB-1 labelling index of the oesophageal carcinomas. The synthetic (S) phase fraction of diploid tumours bore no relation to the patients' survival or MIB-1 score. CONCLUSIONS: Flow cytometry was not as useful as the MIB-1 labelling index in predicting the biological characteristics of the tumours and the prognosis of patients with oesophageal squamous cell carcinomas. This study does not support the routine use of DNA flow cytometric analysis in oesophageal cancers.

Aged↗
PubMed1996

Measurement of extent of spread of oesophageal squamous carcinoma by serial sectioning.

OBJECTIVES: (1) To examine the prevalence and extent of intramural metastasis in squamous cell carcinomas of the oesophagus so as to delineate the resection margins for these tumours; (2) to devise an appropriate method for measurement of these lesions which takes into account of the contraction of the specimens after resection. METHODS: Oesophagectomy specimens were prospectively collected from 96 patients (87 males, nine females) with primary oesophageal squamous cell carcinoma over a two year period. The sizes of the tumours were measured in situ, after resection and after application of muscle relaxant (to regain their in situ length). The specimens were then serially sectioned for histological examination. RESULTS: The sizes of the tumours measured after application of muscle relaxant roughly corresponded to those measured in situ. Intramural metastasis was observed in 26% of the cases. Sixty four per cent (16 cases) of these were on the oral side, 72% (18 cases) on the gastric side, and 25% (nine cases) on both sides of the tumours. The most distant extent of intramural metastasis from the primary tumour was from 0.5 cm to 7.7 cm (mean = 3.4 cm) on the oral side, and 0.5 to 9.5 cm (mean 4 cm) on the gastric aspect of the tumour. Intramural metastasis was seen only in patients in whom the primary cancer had deep muscle infiltration. Multiple neoplastic lesions could be detected in 33% of the patients. Both intramural metastasis and multiple neoplastic lesions were associated with extensive lymph node infiltration. However, they had different histological features and extent of infiltration. CONCLUSIONS: Intramural metastasis was frequently observed in oesophageal squamous cell carcinoma. This implies that excision with wide margins should be considered for local control of the disease.

Adult↗
PubMed1996

Altered endothelium-dependent responses in lambs with pulmonary hypertension and increased pulmonary blood flow.

To investigate early endothelial function associated with increased pulmonary blood flow, vascular shunts were placed between the ascending aorta and main pulmonary artery in 18 late-gestation fetal sheep. Four weeks after delivery, the lambs were instrumented to measure vascular pressures and blood flows, and blood was collected to measure plasma concentrations of guanosine 3',5'-cyclic monophosphate [cGMP, the second messenger to nitric oxide (NO)-mediated vasodilation] and L-arginine (the precursor for NO synthesis). The responses to the endothelium-dependent vasodilators acetylcholine (ACh, 1.0 microgram/kg) and ATP (0.1 mg.kg-1.min-1), the endothelium-independent vasodilators M & B-22948 (a cGMP-specific phosphodiesterase inhibitor, 2.5 mg/kg) and inhaled NO (40 ppm), and N omega-nitro-L-arginine (an inhibitor of NO synthase, 5 mg/kg) were then compared with responses in 12 age-matched controls. Vasodilator responses in control lambs were determined during pulmonary hypertension induced by U-46619 (a thromboxane A2 mimic). Shunted lambs displayed a selective impairment of endothelium-dependent pulmonary vasodilation, an augmented pulmonary vasoconstricting response to NO synthase inhibition, increased plasma cGMP concentrations, and decreased L-arginine concentrations. Taken together, these data suggest that lambs with pulmonary hypertension and increased pulmonary blood flow have early aberrations in endothelial function, as manifested by increased basal NO activity, that cannot be further increased by agonist-induced endothelium-dependent vasodilators.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

Endothelin receptor blockade does not alter the increase in pulmonary blood flow due to oxygen ventilation in fetal lambs.

At birth, pulmonary vasodilation occurs during rhythmic distension of the lungs with oxygen. Both mechanical and humoral factors are involved, including the release of vasoactive substances such as prostacyclin and endothelium-derived nitric oxide (EDNO). However, the exact mechanisms remain unclear. Because endothelin-1 (ET-1) produces potent pulmonary vasodilation in the fetus via EDNO release and ET-1 concentrations are increased at birth, we considered that ET-1 activity may participate in the pulmonary vasodilation that occurs with O2 ventilation. Therefore, we studied and compared the changes in pulmonary hemodynamics associated with in utero O2 ventilation with and without ET-1 receptor blockade induced by an infusion of Ro 47-0203 (Bosentan, a nonselective ET receptor antagonist), in 13 late-gestation fetal lambs. In all fetal lambs, prostaglandin synthesis was prevented by an infusion of meclofenamate, and ductus arteriosus constriction was prevented by prior formalin infiltration. The infusion of Ro 47-0203 blocked the decrease in pulmonary vascular resistance induced by injections of either ET-1 (-0.985 versus +0.012 mm Hg/mL/min/100 g of lung, p < 0.05) or 4-Ala-ET-1 (an ETb receptor agonist) (-0.717 versus -0.052 mm Hg/mL/min/100 g of lung, p < 0.05). However, ET receptor blockade did not change the increase in pulmonary blood flow or decrease in pulmonary vascular resistance associated with in utero O2 ventilation. This study suggests that endogenous ET-1 activity does not play an important role in the vasodilatory response to ventilation with O2 in utero.

Animals↗
PubMed1996

Measuring quality of life in different cultures: translation of the Functional Living Index for Cancer (FLIC) into Chinese and Malay in Singapore.

Quality-of-life assessment has become an accepted method of evaluation in clinical medicine. The technique is based on a patient's self-assessment of physical, psychological, and social function, as well as the effects of distressing physical symptoms. The most important aspect of quality-of-life assessment is that it brings into focus a patient-centred view of health outcome, which is broader than the physiologic measures which predominate in Western medicine. Strategies for the development and use of assessment questionnaires have evolved over the past 15 years, and numerous questionnaires have been created. Most originate in Western societies, with English as the most common language of development. Adapting such questionnaires for use in other language and cultural settings is an imprecise practice. Language translation and equivalent cultural meaning must both be addressed. This paper reports on the language translation process and results for the Functional Living Index for Cancer (FLIC) as translated into Chinese and Malay in Singapore. We employed a step-wise process beginning with translation/back translation, followed by structured pilot field trials and population sampling. Taped versions of the questionnaire were devised to meet illiteracy problems in the sample population. Paired comparisons of the Chinese and Malay versions of individual questions with their English counterparts show good correlations and similar means most of the time. Factor analysis on a population sample of 246 (112 Chinese, 35 Malay and 98 English speaking) with cancers of minimal, extensive or palliative extent is convergent with that obtained on a North American population. However, a separate analysis of the Chinese questionnaires showed some differences in factor pattern. Specific language and cultural translation difficulties are discussed. Of note is the predicted significant decrease in total FLIC scores with extent of disease within each of the language preference populations, which provides some evidence for the validity for each language version in the Singapore culture(s). Thus, the FLIC translations into Malay and Chinese in Singapore can be considered for use in local trials, subject to ongoing evaluation.

Activities of Daily Living↗
PubMed1996

Four cases of developmental foregut cysts.

Four patients with developmental foregut cysts were seen in the Singapore General Hospital between 1991 and 1994. Three had bronchogenic cysts while one had features consistent with both enteric and bronchogenic origin. Among those patients with bronchogenic cysts, only one was symptomatic, having presented with cough and dysphagia. Two other patients presented incidentally on chest radiographs done for pre-National Service enlistment while one patient was picked up when a repeat chest radiograph was done following a course of antibiotics. The diagnosis of our first patient with the symptomatic bronchogenic cyst was based on barium swallow and a computerised tomographic scan of the thorax. Two patients were diagnosed on histology following open thoracotomy and surgical resection of the cysts to have a bronchogenic and a cyst of mixed origin as described above respectively. The last patient who underwent video-assisted thoracoscopic surgery with resection of the cyst was confirmed histologically to have a bronchogenic cyst.

Adult↗
PubMed1995

Dosimetric evaluation of the conformation of the multileaf collimator to irregularly shaped fields.

PURPOSE: The goal of this study was to evaluate the dosimetric characteristics of geometric MLC prescription strategies and compare them to those of conventional shielding block. METHODS AND MATERIALS: Circular fields, square fields, and 12 irregular fields for patients with cancer of the head and neck, lung, and pelvis were included in this study. All fields were shaped using the MLC and conventional blocks. A geometric criterion was defined as the amount of area discrepancy between the MLC and the prescription outline. The "least area discrepancy" (LAD) of the MLC conformation was searched by selecting the collimator angle, meanwhile keeping a preselected position along the width of the leaf into the prescribed field. Five LAD conventions were studied. These included the LAD-0, LAD-1/3, LAD-1/2, and LAD-2/3 that inserted the leaves at the 0, 1/3, 1/2, and 2/3 of the leaf end into the prescription field, respectively. In addition, the LAD optimization was applied to the transecting (TRN) approach for leaf conformation that prescribed an equal area of overblocking and underblocking under each leaf. Film dosimetry was performed in a 20 cm polystyrene phantom at 10 cm depth 100 cm from source to axis distance (SAD) for both 6 and 18 MV photons with each of the above MLC conformations and conventional blocks. The field penumbra width, defined as the mean of the separation between the 20% and 80% isodose lines along the normal of the prescription field edge, was calculated using both the MLC and conventional block film dosimetry and compared. In a similar way, the d20 is defined as the mean separation between the 20% isodose line and the prescription field edge, and the d80 is defined as the mean separation between the 80% isodose line and the prescription field edge. RESULTS: The field penumbra width for all MLC conventions was approximately 2 mm larger than that of the conventional block. However, there was a larger variation of the separation distribution in the penumbra region of the irregular fields for the MLC, which had a standard deviation of 1 mm (a factor of 5 larger than the conventional block). The dosimetry for the circular fields showed that the LAD-TRN, LAD-1/2, and LAD-1/3 approximated the conventional blocking well in terms of d20 and d80; however, no single convention produced the best conformation for both measures. The dosimetric result of the patient treatment fields was similar for all sites. The LAD-1/3, LAD-1/2, and LAD-TRN strategies conformed to within 1 to 1.5 mm of the d80 of the conventional block for both 6 MV and 18 MV, respectively. The LAD-1/2 and LAD-TRN conformations were virtually identical, although it is proven analytically that the LAD-1/2 convention has the least overall area discrepancy of all conventions. CONCLUSIONS: The five MLC conformation conventions resulted in similar dosimetric penumbrae for all field shapes studied. The LAD-1/3, LAD-TRN, and LAD-1/2 produced the more favorable approximation to conventional block. The field penumbra width, although useful for evaluating irregular field shapes, could not describe the large local variations in the penumbra along the field edge for the MLC. These local variations could be of clinical concern when they appear near vital organs. However, the variation in a local region can potentially be reduced by minimizing the jaggedness of the leaf steps in that local region. The dosimetric results were useful as guidelines for the clinicians in the evaluation and adjustment of MLC leaf positions.

Head and Neck Neoplasms↗
PubMed1995

The cumulative verification image analysis tool for offline evaluation of portal images.

PURPOSE: Daily portal images acquired using electronic portal imaging devices contain important information about the setup variation of the individual patient. The data can be used to evaluate the treatment and to derive correction for the individual patient. The large volume of images also require software tools for efficient analysis. This article describes the approach of cumulative verification image analysis (CVIA) specifically designed as an offline tool to extract quantitative information from daily portal images. METHODS AND MATERIALS: The user interface, image and graphics display, and algorithms of the CVIA tool have been implemented in ANSCI C using the X Window graphics standards. The tool consists of three major components: (a) definition of treatment geometry and anatomical information; (b) registration of portal images with a reference image to determine setup variation; and (c) quantitative analysis of all setup variation measurements. The CVIA tool is not automated. User interaction is required and preferred. Successful alignment of anatomies on portal images at present remains mostly dependent on clinical judgment. Predefined templates of block shapes and anatomies are used for image registration to enhance efficiency, taking advantage of the fact that much of the tool's operation is repeated in the analysis of daily portal images. RESULTS: The CVIA tool is portable and has been implemented on workstations with different operating systems. Analysis of 20 sequential daily portal images can be completed in less than 1 h. The temporal information is used to characterize setup variation in terms of its systematic, random and time-dependent components. The cumulative information is used to derive block overlap isofrequency distributions (BOIDs), which quantify the effective coverage of the prescribed treatment area throughout the course of treatment. Finally, a set of software utilities is available to facilitate feedback of the information for treatment plan recalculation and to test various decision strategies for treatment adjustment. CONCLUSIONS: The CVIA tool provides comprehensive analysis of daily images acquired with electronic portal imaging devices. Its offline approach allows characterization of the nature of setup variation for the individual patient that would have been difficult to deduce using only a few daily or weekly portal images. Distribution of the tool will help establish an important database of setup variation from many clinics. The information derived from CVIA can also serve as the foundation to integrate treatment verification, treatment planning, and treatment delivery.

Computer Peripherals↗
PubMed1995

Effects of treatment setup variation on beam's eye view dosimetry for radiation therapy using the multileaf collimator vs. the cerrobend block.

PURPOSE: The purpose of this study is to quantify and compare retrospectively the effects of treatment setup variation on beam's eye view (BEV) dosimetry for radiation therapy using a multileaf collimator (MLC) vs. cerrobend block. METHODS AND MATERIALS: A study was performed on a group of 18 patients with cancer of the head and neck, lung, and pelvis who were treated with irregularly shaped fields. The BEV dosimetry of the fields shaped with cerrobend blocks and the MLC was measured with films at the depth of dose prescription in a solid water phantom. A "one-half-leaf" insertion convention was used to shape the MLC. In addition, an average of 15 sequential daily port films was taken per patient during the course of radiotherapy. The port films were aligned with the prescription film for each patient. Systematic error and random error of treatment setup for each patient were calculated. The effects of setup variation were incorporated by convolving the patient portal imaging data with the corresponding BEV film dosimetry. Two parameters were used to quantify the BEV dosimetry. First, the field penumbra width was calculated, which represented the average of the normal separations between 20 and 80% isodose lines along the prescription outline. Second, the ratio of areas covered by the 90 and 20% isodose lines, A90/20, was determined. The BEV dosimetry was then characterized with and without the effects of treatment setup variation. In addition, the difference in BEV dosimetry between the cerrobend block and the MLC was used to estimate the corresponding changes in tumor control probability (TCP). These changes were also compared to the changes in TCP for the treatment with or without the effects of random setup variation. RESULTS: With or without daily setup variation, the use of cerrobend block was more favorable than the MLC in terms of the field penumbra width and A90/20 for all treatment sites. In the absence of daily variation, the MLC field penumbra width was on average 1.3 mm larger than that of the cerrobend block, and 0.9 mm larger in the presence of daily setup variation. Similarly, the ratio A90/20 of the cerrobend block was on average 0.03 larger than that of MLC without daily setup variation, and 0.02 with daily setup variation. The difference in field penumbra width and A90/20 between the MLC and the cerrobend block was slightly reduced due to the effects of daily setup variation. For both the cerrobend block and the MLC, daily setup variation produced a significant increase in the field penumbra width, 2.3 mm for the cerrobend block and 1.9 mm for the MLC, and a decrease in the A90/20, 0.06 for the former and 0.05 for the latter. The change due to the daily setup variation was about a factor of 2 larger than the changes due to replacing the cerrobend block with the MLC. Using the TCP model, the change in TCP due to the daily setup variation was more than a factor of 3 larger than the change in TCP due to replacing the cerrobend block with the MLC. It was noted that the average changes in the penumbra, the A90/20 and the TCP calculated for the patient population did not adequately describe the changes for the individual patient. CONCLUSION: Our results do not show significant dosimetric differences between the MLC and the cerrobend block in conventional radiation treatment, whether or not daily setup variation was taken into consideration. The effects of daily setup variation alone produced a larger dosimetric change. The same results were obtained when the data were applied to calculate changes in TCP. For optimal radiation therapy, efforts should be concentrated on reducing daily setup variation. Our results also demonstrate the importance of frequent evaluation of MLC treatment using electronic portal imaging devices.

Equipment Design↗
PubMed1995

A role for nucleosome assembly in both silencing and activation of the Xenopus TR beta A gene by the thyroid hormone receptor.

We have assembled the thyroid hormone-inducible promoter of the Xenopus thyroid hormone receptor (TR)beta A gene into chromatin using replication-coupled and -independent assembly pathways in vivo. We establish that heterodimers of TR and 9-cis retinoic acid receptors (RXR) can bind to their recognition sites within chromatin both in vivo and in vitro and alternately repress or activate transcription dependent on the absence or presence of thyroid hormone. Maximal transcriptional repression requires the presence of unliganded TR/RXR heterodimers during replication-coupled chromatin assembly. We demonstrate an increase in transcription directed by the TR beta A promoter of over two orders of magnitude in vivo, following the addition of thyroid hormone. This increase in transcription involves the relief of the repressed state that is established by the unliganded TR/RXR heterodimer during replication-coupled chromatin assembly. The association of thyroid hormone with the chromatin-bound TR/RXR heterodimer leads to the disruption of local chromatin structure in a transcription-independent process. Thus, chromatin structure has multiple roles in the regulation of TR beta A gene expression in vivo: The TR/RXR heterodimer recognizes the response element within chromatin, TR/RXR makes use of the chromatin assembly process to silence transcription more efficiently, and TR/RXR directs the disruption of local chromatin structure in response to thyroid hormone.

Animals↗
PubMed1995

Pamidronate treatment of the neurologic sequelae of pagetic spinal stenosis.

Spinal stenosis is a serious complication of Paget's disease of bone. Surgical decompression has a high complication rate and is not always effective. Medical therapy with bisphosphonates is established treatment in other forms of Paget's disease. To our knowledge, this is the first report of the use of intravenous pamidronate disodium as the sole treatment of lower limb weakness attributable to pagetic spinal stenosis. Our patient has been restored to independent living and has maintained his remission, with repeated treatment, for more than 5 years.

Aged↗