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Biomedical subjects

S Chan

Publications and source records attributed to S Chan.

At least 19 recordsLinked to original sources
PubMed1999

Complications associated with pegging hydroxyapatite orbital implants.

OBJECTIVE: Prior studies of hydroxyapatite orbital implant complications have primarily focused on complications of the implant itself with only occasional mention of the complications associated with the peg system. This in part may be because of a low rate of pegging and, thus, a small sample size to evaluate. Therefore, a full range of complications that can occur with pegging has not been presented. The objective of this study was to determine the complications associated with pegging and to discuss ways to manage them. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS/INTERVENTION: The authors analyzed all of the complications associated with pegging 165 of a possible 275 hydroxyapatite implants implanted by 2 surgeons over 7 years. MAIN OUTCOME MEASURES: The following data were recorded: type of surgery performed, size of implant used, type of hydroxyapatite used, peg system used, time of pegging, follow-up duration, problems encountered, and treatment. RESULTS: Sixty-two (37.5%) of the 165 patients who had pegged implants were found to have problems with their pegs. Twenty-one (33.8%) of the 62 patients with peg problems had more than 1 peg-related problem. Complications associated with pegging included discharge (37%; 23 of 62), pyogenic granulomas (30.6%; 19 of 62), peg falling out (29%; 18 of 62), poor transfer of movement (11.2%; 7 of 62), clicking (11.2%; 7 of 62), conjunctiva overgrowing peg (4.8%; 3 of 62), poor-fitting sleeve (4.8%; 3 of 62), part of sleeve shaft visible (4.8%; 3 of 62), peg drilled on an angle (4.8%; 3 of 62), hydroxyapatite visible around peg hole (3.2%; 2 of 62), peg drilled off-center (3.2%; 2 of 62), popping peg (3.2%; 2 of 62), and excess movement of peg (3.2%; 2 of 62). The most serious complication occurring in two individuals (3.2%) was implant infection requiring implant removal. CONCLUSION: There are several potential complications that can occur after pegging the hydroxyapatite implant. These problems are generally of a minor nature but often require additional patient visits that would not ordinarily have been required if the peg was not in place. The most serious peg problem is implant infection, which may necessitate implant removal. These potential peg problems should be reviewed with the patient before the procedure is performed.

Adolescent↗
PubMed1999

Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice.

Alzheimer's disease is characterized by amyloid beta-peptide deposition, synapse loss, and neuronal death, which are correlated with cognitive impairments. Mutations in the presenilin-1 gene on chromosome 14 are causally linked to many cases of early-onset inherited Alzheimer's disease. We report that synaptosomes prepared from transgenic mice harboring presenilin-1 mutations exhibit enhanced elevations of cytoplasmic calcium levels following exposure to depolarizing agents, amyloid beta-peptide, and a mitochondrial toxin compared with synaptosomes from nontransgenic mice and mice overexpressing wild-type presenilin-1. Mitochondrial dysfunction and caspase activation following exposures to amyloid beta-peptide and metabolic insults were exacerbated in synaptosomes from presenilin-1 mutant mice. Agents that buffer cytoplasmic calcium or that prevent calcium release from the endoplasmic reticulum protected synaptosomes against the adverse effect of presenilin-1 mutations on mitochondrial function. Abnormal synaptic calcium homeostasis and mitochondrial dysfunction may contribute to the pathogenic mechanism of presenilin-1 mutations.

Alzheimer Disease↗
PubMed1999

Effect of beta-blockade on baroreceptor and autonomic function in heart failure.

Although beta-adrenoreceptor antagonists appear to be beneficial in chronic heart failure there is little information on their effects on autonomic and baroreceptor function which may have important prognostic implications. We sought to determine first whether beta-adrenoreceptor blockade will improve baroreceptor function and vagal tone in chronic heart failure, and second whether there were any differences between standard therapy with metoprolol and the second-generation vasodilating beta-blocker celiprolol. In this double-blind randomized placebo-controlled study 50 patients with stable chronic heart failure received either celiprolol 200 mg daily, metoprolol 50 mg twice daily or placebo for 12 weeks after a 4-week dose titration period. Thirty-five healthy normal subjects were also studied. Baroreceptor gain was assessed non-invasively by cross-spectral analysis of R-R and systolic blood pressure low- and high-frequency components (the alpha angle) during controlled respiration. High-frequency power was used as a measure of vagal modulation. Satisfactory recordings for analysis were obtained in 31 patients with heart failure. The results showed that at baseline baroreceptor gain (alphaHF) was significantly depressed in patients with heart failure compared with the normal control group (4.95+/-0. 55 versus 11.73+/-1.32 ms/mmHg, P<0.0001). After 12 weeks of treatment with metoprolol baroreceptor gain improved significantly whether measured while supine (P=0.03) or standing (P=0.009), and this was associated with a significant increase in R-R HF power (P=0. 008). There were no significant changes after treatment with celiprolol or placebo. We conclude that metoprolol but not celiprolol therapy restores baroreceptor gain towards normal and increases vagal tone in chronic heart failure. The ancillary properties of celiprolol do not appear to provide any advantages over metoprolol for the restoration of autonomic and baroreceptor function in heart failure.

Adrenergic beta-Antagonists↗
PubMed1998

Visualization of CD4/CD8 T cell commitment.

A system to innocuously visualize T cell lineage commitment is described. Using a "knock-in" approach, we have generated mice expressing a beta-galactosidase reporter in place of CD4; expression of beta-galactosidase in these animals appears to be an accurate and early indicator of CD4 gene transcription. We have exploited this knock-in line to trace CD4/CD8 lineage commitment in the thymus, avoiding important pitfalls of past experimental approaches. Our results argue in favor of a selective model of thymocyte commitment, demonstrating a fundamentally symmetrical process: engagement of either class of major histocompatibility complex (MHC) molecule by a differentiating CD4(+)CD8(+) cell can give rise to T cell antigen receptor (TCR)hi thymocytes of either lineage. Key findings include (a) direct demonstration of a substantial number of CD4-committed, receptor/coreceptor-mismatched cells in MHC class II- deficient mice, a critical prediction of the selective model; (b) highly efficient rescue of such "mismatched" intermediates by forced expression of CD8 in a TCR transgenic line, and an explanation of why previous experiments of this nature were less successful-a major past criticism of the selective model; (c) direct demonstration of an analogous, though smaller, population of CD8-committed mismatched intermediates in class I-deficient animals. Finally, we found no evidence of a CD4 default pathway.

Animals↗
PubMed1998

Prospective magnetic resonance imaging identification of focal cortical dysplasia, including the non-balloon cell subtype.

The purpose of this study was to determine the role of high-resolution T2-weighted fast multiplanar inversion-recovery (FMPIR) magnetic resonance (MR) imaging in detecting and delineating microscopic focal cortical dysplasia (FCD). We performed MR scans with FMPIR on 42 patients with suspected neocortical epilepsy. Ten MR studies were read prospectively as showing FCD; these case histories, electroencephalographic studies, and neuroimaging data were reviewed. Eight of these patients subsequently underwent focal cortical resection guided by intraoperative electrocorticography. The MR findings were correlated with pathological findings in these 8 patients. For purposes of radiological-pathological correlation, the FCD lesions were divided into two classes. Radiological classification was based on the absence (type A) or presence (type B) of T2 prolongation of the subcortical white matter. Pathological grading as type I or type II was based on a previously described pathological grading system. Specific MR findings associated with FCD included focal blurring of the gray-white matter interface (n = 9), thickening of the cortical ribbon (n = 7), and T2 prolongation of the subcortical white matter (n = 4). In 3 patients, the only MR finding that suggested FCD was localized blurring of the gray-white matter junction. In 2 of these 3 patients, the MR diagnosis of FCD could be made only by FMPIR. FCD was confirmed histologically in 7 of 8 patients, with insufficient tissue for complete histopathological evaluation in 1 case. Radiological classification of FCD agreed with pathological classification in 5 of 7 cases. Correlation of MR findings with intraoperative electrocorticography results indicated that the MR study localized the epileptogenic lesion correctly in 8 of 8 cases. Scalp ictal electroencephalographic studies localized the epileptogenic lesion in 5 of 8 cases; positron emission tomographic scans were focally abnormal in 3 of 3 cases. FMPIR MR imaging permitted accurate diagnosis and localization of FCD in all patients with pathologically proved FCD. MR identification of FCD aided presurgical planning and intraoperative management of these patients.

Adolescent↗
PubMed1998

Incident reporting in acute pain management.

Incident reporting is an effective tool for continuous quality improvement in clinical practice. A prospective study on voluntary incident reporting in pain management was conducted at a major teaching hospital in Hong Kong. Over a 12-month period, 53 incidents were reported in 1275 patients who received pain relief treatments which were supervised by the acute pain service. The majority of the incidents were first detected by the pain team. The most common incidents involved delivery circuits, delivery pump and drug administration. A large proportion (81.4%) of the incidents were thought to be preventable. Human factors were involved in 41.9% of the patients reported, most commonly associated with unfamiliar technique/inexperience, inattention and inadequate communication. Four patients developed major morbidity of which two were attributed to inadequate analgesia, while three others had major physiological changes without morbidity. Strategies have been formulated to prevent further occurrence of these incidents. We propose that incident reporting is a potentially useful tool in identifying and preventing adverse events in postoperative pain management.

Acute Disease↗
PubMed1998

The role of bladder neck biopsy in men undergoing radical retropubic prostatectomy with preservation of the bladder neck.

PURPOSE: Radical retropubic prostatectomy is often performed with preservation of the bladder neck. We examine the incidence of benign and malignant prostatic tissue at the bladder neck margin in men undergoing radical retropubic prostatectomy with preservation of the bladder neck for clinically localized prostate cancer. MATERIALS AND METHODS: The study included 100 cases of radical retropubic prostatectomy with preservation of the bladder neck performed by a single surgeon (H. L.). A 2 mm. thick circumferential specimen was excised from the bladder neck, divided into 4 quadrants (anterior, posterior, right and left) and submitted for frozen section examination. The permanent sections from these bladder neck biopsies and the entire surgical specimens were analyzed by a single pathologist (J. M.). RESULTS: The frozen section diagnosis from the bladder neck biopsies were adenocarcinoma, benign prostatic tissue and no prostatic tissue in 3, 38 and 59 cases, respectively. The permanent section diagnosis of the bladder neck biopsies was adenocarcinoma, benign prostatic tissue and no prostatic tissue in 4, 57 and 39 cases, respectively. The sensitivity specificity, and positive and negative predictive values for examination of the surgical specimen to identify benign prostatic tissue was 67, 90, 90 and 65%, respectively. The bladder neck was re-biopsied because of the findings of adenocarcinoma and benign prostatic tissue in 3 and 8 cases, respectively. The initial bladder neck biopsy resulted in pathological down staging to pT2c in only 1 case. Repeat resection of the bladder neck in all cases with 10% or less benign prostatic tissue showed no prostatic tissue, whereas 50% of the cases with more than 10% benign prostatic tissue demonstrated residual benign prostatic tissue. Serum prostate specific antigen was undetectable immediately after radical retropubic prostatectomy in all cases with benign prostatic tissue only. CONCLUSIONS: Preservation of the bladder neck during radical retropubic prostatectomy does not significantly compromise total extirpation of the malignant process. Benign prostatic tissue at the bladder neck margin is relatively common. Examination of the surgical specimen has limited sensitivity, and negative and positive predictive values for the presence of benign prostatic tissue at the bladder neck margin. The impact of benign prostatic tissue as it relates to future malignant transformation is unknown. Submitting frozen section specimens from the bladder neck is reasonable for the younger man who may be at risk from benign prostatic tissue at the bladder neck margin.

Adenocarcinoma↗
PubMed1998

CD4/CD8 lineage commitment: matching fate with competence.

The outcome of positive selection of T lymphocytes is that there is a close match between the lineage adopted by a particular cell (CD4+ or CD8+) and the specificity of the T-cell receptor for the class of Major Histocompatibility Complex molecule recognized. How this match is obtained has been a matter of debate. We review the evidence, from recent and older experiments, that indicates that the process follows a selective logic, rather than an instructive one.

Animals↗
PubMed1998

CADASIL in a North American family: clinical, pathologic, and radiologic findings.

OBJECTIVE: To expand the reported phenotypic range of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). BACKGROUND: Despite numerous patient reports, our knowledge of the phenotypic range of CADASIL remains incomplete. METHOD: We performed clinical, pathologic, and radiologic examinations on members of a family with CADASIL. RESULTS: The proband is a 61-year-old man with a history of migraine and depression who has experienced multiple subcortical infarctions resulting in a stepwise decline. Neuropsychological testing documented a dementia syndrome with frontal lobe features and neurologic examination noted a left hemiparesis and a right-sided palmomental reflex. Brain biopsy with light microscopy revealed a nonatherosclerotic small-vessel angiopathy with periodic acid-Schiff positive granular changes in the media and white matter gliosis, with unremarkable cortex. Genetic testing confirmed a Notch3 mutation. The proband's first cousin has a history of depression, one seizure possibly resulting from an acute stroke, and a learning disorder. Neuropsychological testing demonstrated deficits in executive function and neurologic examination noted persistent extraneous adventitial movements, poor coordination, and primitive reflexes. Skin biopsy with electron microscopy demonstrated granular osmiophilic material within the basement membrane of vascular smooth muscle cells, which is considered to be pathognomonic of CADASIL. The proband's older son and younger son have histories of migraine and depression, respectively, and both also had learning disorders. MRI revealed diffuse white matter disease extending into the temporal lobes, and lacunar infarctions in these four nonhypertensive patients. Other family members have experienced migraine, recurrent stroke, dementia, and depression. CONCLUSIONS: CADASIL is a genetic basis for vascular dementia that may be manifest earlier in life than previously reported.

Adult↗
PubMed1998

Effects of combined endurance and strength training on left ventricular morphology in male and female rowers.

The effects of 10 weeks of combined endurance and strength training on left ventricular (LV) morphology, muscular strength, maximal oxygen consumption (VO2max) and rowing performance were assessed. Twenty-five subjects (eight males, mean age 23.0 +/- 6.1 years, and 17 females, 22.7 +/- 5.0 years) were tested at baseline and after five and 10 weeks of training. Combined training was associated with significant improvements in VO2max, rowing performance and muscular strength after 10 weeks of training. A significant increase in LV diastolic dimension was found in males after 10 weeks of training; however, no significant alteration was found for any other measured echocardiographic variable. Therefore, with the exception of LV diastolic dimension in males, 10 weeks of combined endurance and strength training appears to be an insufficient stimulus to elicit significant alterations in LV morphology despite changes in VO2max, muscular strength or rowing performance.

Female↗
PubMed1998

Somatic gene therapy. Present situation and future perspective.

The ultimate goal in the management of inherited as well as acquired diseases is a rational therapy with the aim to eliminate the underlying biochemical defects, rather than a symptomatic treatment. Among other approaches somatic gene therapy is a promising candidate to meet these objectives and appears to have the potential to revolutionize modern medicine. Gene therapy is characterized by the transfer of genetic information to a patient through the use of recombinant DNA technology. Several strategies for the treatment of monogenetic disorders as well as chronical diseases like cancer and AIDS have been used in various somatic gene therapy projects. So far, 329 clinical studies (phases I, I/II and II) with over 2500 patients have been initiated worldwide since 1989. No significant toxicity and adverse side effects have been observed. To allow efficient transfer of the therapeutic genes, a variety of gene delivery techniques have been developed based on viral and non-viral vector systems. For the success of this technology it is vital to achieve regulated and sustained expression of foreign genes in specific target tissues. This will be crucial for the widespread application of somatic gene therapy. So far none for the gene delivery systems is able to meet the requirements of safety, efficiency and specificity demonstrating that vector research will be an important focus in the development of optimized transfer methods. From a regulatory point of view pharmaceutical DNA-products can be regarded as drugs and are therefore subject to the same regulations. Human gene therapy must, however, be limited to manipulations affecting somatic, differentiated cells to prevent the transferred gene from being transmitted to the individual's descendants. Applications for the purpose of 'enhancement' and not for the treatment of diseases are also not acceptable. Under these prerequisites, somatic gene therapy does not raise any new ethical concerns and can be interpreted as a special form of an organ transplantation. A comparison of the different regulatory situations of gene therapy in Europe and the United States demonstrates that for the European countries a uniform regulation is desired. Today somatic gene therapy is still in its infancy. It will continue to be scientifically and technically challenging until simple and effective procedures will have been developed. Demonstration of its clinical efficacy especially in the long term will have to be the next step. Looking at the history of biotechnology and the success of the biotechnology industry that is now providing safe and efficient products from recombinant DNA-technology there is little doubt that gene therapy will become a successful treatment for various indications in the next decade. The purpose of this article is to review the current status of the development in somatic gene therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Technical and clinical aspects of spectrometric analysis of trace elements in clinical samples.

The capabilities of ICP-MS far exceed the slow, single-element analysis of GFAAS for determination of multiple trace elements. Additionally, its sensitivity is superior to that of DCP, ICP, and FAAS. The analytic procedure for ICP-MS is relatively straightforward and bypasses the need for digestion in many cases. It enables the physician to identify the target trace element(s) in intoxication cases, nutritional deficiency, or disease, thus eliminating the treatment delays experienced with sequential testing methods. This technology has its limitations as well. The ICP-MS cannot be used in the positive ion mode to analyze with sufficient sensitivity highly electronegative elements such as fluorine, because F+ is unstable and forms only by very high ionization energy. The ICP mass spectrometers used in most commercial laboratories utilize the quadrupole mass selector, which is limited by low resolution and, thus, by the various interferences previously discussed. For example, when an argon plasma is used, selenium (m/e 80) and chromium (m/e 52) in serum, plasma, and blood specimens are subject to polyatomic and molecular ion interferences. Low-resolution ICP mass spectrometers can therefore be used to analyze many trace elements, but they are not universal analyzers. High-resolution ICP-MS can resolve these interferences, but with greater expense. With the advent of more research and development of new techniques, some of these difficulties may be overcome, making this technique even more versatile. Contamination during sample collection and analysis causes falsely elevated results. Attention and care must be given to avoid contamination. Proper collection devices containing negligible amounts of trace elements should be used. Labware, preferably plastic and not glass, must be decontaminated prior to use by acid-washing and rinsed with [table: see text] de-ionized water. A complete description of sample collection and contamination has been written by Aitio and Jarvisalo as well as by Chan and Gerson. Lutz et al observed the ranges in blood shown in Table 4. We have adopted the ranges listed in Table 5 in urines of healthy, ambulatory, and community-dwelling individuals through a limited in-house study and review of literature. In conclusion, differentiation of trace element abnormalities (primary intoxication or disease versus secondary underlying disease) can be made only by utilizing results from trace element analyses in clinical specimens, medical history, and careful observation of symptoms. Repeat analysis on a second specimen collection is recommended when contamination is suspected.

Body Fluids↗