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Biomedical subjects

A Chang

Publications and source records attributed to A Chang.

At least 37 records · Page 2Linked to original sources

Percutaneous arterial closure in peripheral vascular disease: a prospective randomized evaluation of the Perclose device.

BACKGROUND: Patients with peripheral vascular disease have been excluded from initial studies of percutaneous suture-mediated closure devices (SMCD) despite representing a significant proportion of those requiring endovascular intervention. We sought to determine whether these devices could be safely used in patients with peripheral vascular disease. METHODS: Patients were stratified into two groups and five subgroups on the basis of indication for arteriography, and they were prospectively randomized at the end of the procedure to receive either the SMCD or manual compression. Ankle-brachial index was determined and duplex ultrasound scanning of the accessed femoral artery was performed, before and after the procedure. Ultrasound data included peak systolic velocity, minimum intraluminal vessel diameter, and presence or absence of calcified plaque. Time to hemostasis, ambulation, and discharge were recorded, and major or minor complications were noted. RESULTS: Of 102 patients included in the study, 52 patients were randomized to receive the SMCD. There was no difference in ankle-brachial index, minimum intraluminal vessel diameter, or peak systolic velocity in the accessed vessel after closure with SMCD or manual compression. Time to hemostasis, ambulation, and discharge was significantly less in the SMCD group (P =.001). Presence of calcified plaque was not associated with complications (P =.146). In the SMCD group, hemostasis was achieved with 49 of 52 devices (94.2%). There were six complications (5.9%), two of which were major and required operative intervention. All complications were hemorrhagic and not occlusive. There was no difference in overall complication rate between SMCD (7.7%) and manual compression (4.0%) groups (P =.678). No infection was noted in any of the 102 patients. CONCLUSIONS: Suture-mediated percutaneous arterial closure can be safely performed in patients with peripheral vascular disease, even in the presence of calcified plaque. This closure technique enables shorter time to hemostasis, ambulation, and hospital discharge. There are observed differences in minor, but not major, complication rates for MC versus percutaneous arterial closure in patients with peripheral vascular disease, but these differences did not achieve statistical significance in this small series.

Aged↗

Facial anthropometry of Hong Kong Chinese babies.

OBJECTIVES: To provide a database of the craniofacial measurements of Chinese infants born in Hong Kong. DESIGN: Prospective cross-sectional study. SETTING AND SAMPLE POPULATION: A total of 2371 healthy singleton, born consecutively at the Prince of Wales Hospital and the Union Hospital from June 1998 to June 2000, were included in the study. The range of gestation was 33-42 weeks. MEASUREMENTS AND RESULTS: Measurements included facial width (FW), facial height (FH), nasal length (NL), nasal width (NW), and length of the philtrum (PhilL). The facial, nasal, nasofacial and nasozygomatic indices were derived. The data show generally higher values for males in the parameters measured. The various indices remained remarkably constant and did not vary significantly between the two genders or with gestation. When compared with previously published data for white people term babies, Chinese babies have similar NW but shorter philtrum length. CONCLUSION: The human face appears to grow in a remarkably constant fashion as defined by the various indices of facial proportions. This study establishes the first set of gestational age-specific standard of such craniofacial parameters for Chinese new-borns, potentially enabling early syndromal diagnosis. There are significant inter-racial differences in these craniofacial parameters.

Asian People↗

Craniofacial anthropometry of Hong Kong Chinese babies: the eye.

OBJECTIVES: To provide a database of the canthal measurements of Chinese infants born in Hong Kong. DESIGN: Prospective cross-sectional study. SETTING AND SAMPLE POPULATION: A total of 2,371 healthy singleton, born consecutively at the Prince of Wales Hospital and the Union Hospital from June 1998 to June 2000, were included in the study. The range of gestation was 33-42 weeks. MEASUREMENTS AND RESULTS: Canthal parameters were measured and included the outer canthal distance (OCD), intercanthal distance (ICD) and palpebral fissure length (PFL). The data generally show higher values for males in the parameters measured. The measurements were also compared with data published overseas. PFL and OCD were significantly larger in Hong Kong Chinese newborn babies, whereas ICD was smaller. CONCLUSION: This study establishes the first set of gestational age-specific standard of such craniofacial parameters for Chinese newborn babies, potentially enabling early syndromal diagnosis. There are significant inter-racial differences in these canthal parameters.

Algorithms↗

Updated gestational age specific birth weight, crown-heel length, and head circumference of Chinese newborns.

OBJECTIVE: To construct gestation specific standards of birth weight, crown-heel length, and head circumference of Chinese infants. DESIGN: A prospective cross sectional population study. METHODS: The birth weight, crown-heel length, and head circumference were prospectively measured using standard equipment in newborns delivered at 24-42 weeks gestation in the maternity units of 10 public hospitals and two private hospitals in Hong Kong. The findings were used to construct gestation specific standards of these variables. The LMS method using maximum penalised likelihood was used to perform model fitting. The results were compared with those obtained from a cohort of infants born in the same locality between 1982 and 1986. RESULTS: From October 1998 to September 2000, a total of 10 032 infants were measured, representing 9.6% of the total deliveries in Hong Kong during that period. An extra 307 infants with gestation < or = 35 weeks were recruited from October 2000 to June 2001. Each of the three variables showed a normal distribution at each gestational week. Gestation specific reference standards for each variable were constructed for male and female infants separately. Comparison with the 1982-1986 cohort showed a significant secular trend to increased birth weight. The trend was small, but significant, for crown-heel length and head circumference. CONCLUSION: These growth standards will provide useful references for the care of newborns of ethnic Chinese origin. These standards, especially that for birth weight, should be updated regularly.

Birth Weight↗

Human kallikrein gene 13 (KLK13) expression by quantitative RT-PCR: an independent indicator of favourable prognosis in breast cancer.

Kallikreins are a group of serine proteases with diverse physiological functions. KLK13 (previously known as KLK-L4) is a novel kallikrein gene located on chromosome 19q13.4 and shares a high degree of homology with other kallikrein family members. Many kallikrein genes were found to be differentially expressed in various malignancies, and their regulation is controlled by steroid hormones in prostate and breast cancer cell lines. We studied the expression of KLK13 by quantitative reverse transcriptase-polymerase chain reaction in 173 patients with epithelial breast carcinoma. An optimal cutoff point equal to the 40th percentile was defined, based on the ability of KLK13 to predict disease-free survival. KLK13 values were then associated with other established prognostic factors and with disease-free survival and overall survival. Higher positivity for KLK13 expression was found in older, oestrogen receptor positive patients. In univariate analysis, KLK13 expression is a significant predictor of improved disease-free survival and overall survival (P<0.001 and P=0.009, respectively). Cox multivariate analysis indicated that KLK13 was an independent prognostic variable in the subgroups of patients with Grade I-II tumours and in patients who were oestrogen receptor and progesterone receptor positive, and node positive. Hazard ratios derived from Cox analysis, related to disease-free survival and overall survival were 0.22 (P=0.001) and 0.24 (P=0.008), respectively, for the Grade I-II group; 0.36 (P=0.008) and 0.44 (P=0.038), respectively, for the node positive group and 0.36 (P=0.008) and 0.18 (P=0.008), respectively, for the oestrogen receptor positive group. The adjusted hazard ratio for progesterone receptor positive patients for disease-free survival was 0.25 (P=0.012). For patients in the node positive and oestrogen receptor positive subgroup (n=51) the adjusted hazard ratio was 0.25 (P=0.006) and for the node positive and progesterone receptor positive subgroup (n=46) the hazard ratio was 0.24 (P=0.008). Taken together, these data suggest that higher KLK13 expression in these subgroups of breast cancer patients is associated with an approximately 55 to 80% reduction in the risk of relapse or death. We conclude that KLK13 expression, as assessed by quantitative reverse transcriptase-polymerase chain reaction, is an independent favourable prognostic marker for breast carcinoma.

Adult↗

Practice distribution in procedural skills training: a randomized controlled trial.

BACKGROUND: "Massed" and "distributed" practice are important concepts in the acquisition of fine motor skills, and may be important in training in procedural skills. METHODS: A total of 41 novice subjects were recruited and randomized to three groups to receive training on the MIST VR surgical trainer. There were 14 subjects in each of groups A and B and 13 subjects in group C. Training comprised 20 min of massed practice for group A, 20 min of distributed practice in 5 min blocks for group B, and 15 min of distributed practice in 5-min blocks for group C. Following the training period, all groups had a 5-min rest period, followed by a 5-min retention test. Comparisons were made between groups A and B, and groups A and C. RESULTS: There was a statistically significant difference between groups A and B (p = 0.023) on the retention test, with group B performing better. The increment between the groups was 19% for the overall score on MIST VR. There were also significant differences in the time taken to complete the task during the training phase (p = 0.023, training blocks 3 and 4). Graphical representation suggests no effect between groups A and C, and statistical analysis confirms that the observed difference in median score is not significant. CONCLUSION: This study demonstrates a benefit for distributed practice over massed practice in learning laparoscopic surgical skills on the MIST VR surgical trainer. This finding has potential implications for skills training in all areas of medicine.

Adult↗

Varicose veins possess greater quantities of MMP-1 than normal veins and demonstrate regional variation in MMP-1 and MMP-13.

BACKGROUND: Studies have reported that structural proteins such as elastin and collagen are decreased in varicose veins compared to normal controls. We hypothesized that the changes observed in varicose vein wall composition may be related to alterations in extracellular matrix remodeling proteins, such as the matrix metalloproteases and serine proteases. In addition we hypothesized that there may be regional variation in the expression of these enzymes within the leg. PATIENTS AND MATERIALS: One-centimeter segments of the proximal and distal greater saphenous vein (GSV) were obtained from patients undergoing ligation and stripping for venous insufficiency (vv) (n = 15) or GSV harvest in conjunction with coronary artery bypass grafting (CABG) (n = 7). All vv patients had incompetence of the GSV by color flow duplex. Vein specimens were examined for MMP-1, 3, and 13, tryptase, and GAPDH mRNA using semiquantitative RT-PCR analysis. Quantification of MMP-1 and 13 (active/latent forms) and tryptase was performed using Western blot analysis. Western blots were analyzed using scanning densitometry and standardized to normal controls and values expressed as the median densitometric index (D.I.). Nonparametric statistical methods (Wilcoxan signed rank test and Mann-Whitney U test) were used for analysis. RESULTS: We were able to amplify MMP-1, MMP-13, and tryptase mRNA from both proximal and distal segments of all greater saphenous veins studied. MMP-3 mRNA, however, was not found in either segment of any of the veins examined. A semiquantitative analysis of RT-PCR products comparing the ratio of MMP-1, MMP-13, or tryptase mRNA to GAPDH mRNA showed no difference between cases and controls nor proximal vs distal vein segments. Western blot analysis revealed larger quantities of MMP-1 in varicose veins than in nondiseased veins from CABG patients (48.0 +/- 36.7 D.I. vs 12.5 +/- 6.8 D.I., P = 0.036). Investigation into the regional variation of proteases revealed lower amounts of MMP-1 in distal than in proximal vein segments (37.9 +/- 35.0 D.I. vs 44.1 +/- 41.6 D.I., P = 0.01). Similarly, we found significantly less MMP-13 in distal segments of varicose veins than in proximal segments (152.8 +/- 130.0 D.I. vs 206.7 +/- 173.3 D.I., P = 0.006). CONCLUSIONS: This study found that MMP-1 protein is increased in varicose veins when compared to controls despite no differences in mRNA expression. In addition we found that there is regional variation of MMP-1 and MMP-13 in diseased varicose veins. Lower leg veins have significantly reduced amounts of these proteolytic enzymes when compared to veins of the upper thigh. These data suggest that posttranscriptional regulatory controls could be responsible for the observed differences.

Adult↗

Quantitative expression of the human kallikrein gene 9 (KLK9) in ovarian cancer: a new independent and favorable prognostic marker.

Many members of the human kallikrein gene family were found to be differentially expressed in various malignancies and some are useful cancer diagnostic/prognostic markers. KLK9 is a newly discovered human kallikrein gene that is expressed in several tissues including thymus, testis, spinal cord, salivary gland, ovary, and skin. Like other kallikreins, the KLK9 gene was found to be regulated by steroid hormones in cancer cell lines. Our purpose is to examine whether quantitative analysis of KLK9 expression has prognostic value in ovarian cancer. We studied the expression of KLK9 by quantitative reverse transcription-PCR in 168 consecutive ovarian tumors of different stages, grades, and histological types, and correlated the expression with clinicopathological parameters, response to chemotherapy, and patients' survival. We found that KLK9 expression was significantly higher in patients with early disease stages (I or II; P = 0.044) and in patients with optimal debulking (P = 0.019). Kaplan-Meier survival curves demonstrated that patients with KLK9-positive tumors have substantially longer progression-free and overall survival (P < 0.001 and P = 0.016, respectively). When the Cox proportional hazard regression analysis was applied to subgroups of patients, KLK9 expression was found to be a significant predictor of progression-free survival in the subgroup of patients with low-grade tumors [hazard ratio (HR), 0.13; P = 0.0015], early stage (HR, 0.099; P = 0.031); and those with optimal debulking (HR, 0.26; P = 0.012). After adjusting for other known prognostic variables, KLK9 retained its independent prognostic value in all of these subgroups of patients. A negative correlation was found between the expression levels of CA125 and KLK9 (rs, 0.350; P = 0.002). Our results indicate that KLK9 is under steroid hormone regulation in ovarian and breast cancer cell lines. Immmunohistochemically, human kallikrein protein (hK9) was localized in the cytoplasm, but not in the nuclei, of the epithelial cells of ovarian cancer tissues. We conclude that KLK9 is a potential new independent favorable prognostic marker for early stage, low-grade, optimally debulked ovarian cancer patients.

Adult↗

Expression and regulation of prostate androgen regulated transcript-1 (PART-1) and identification of differential expression in prostatic cancer.

Prostate androgen regulated transcript 1 (PART-1), is a gene predominantly expressed in the prostate gland and is regulated by androgens in human prostate cancer cell lines. Here, we report additional characteristics of PART-1 tissue expression and hormonal regulation and study its expression profile in human normal and matched prostate cancer tissues. Since PART-1 shows similarity to prostate-specific antigen (PSA) in prostate specificity and regulation, we hypothesized that it may be implicated in prostate carcinogenesis or may be a potential new biomarker. We used reverse transcriptase polymerase chain reaction (RT-PCR) to further characterize PART-1 tissue expression and hormonal regulation in the LNCaP prostate cancer cell line. RT-PCR analysis revealed that PART-1 is expressed not only in the prostate and salivary gland, but also in other tissues, including the thymus and placenta. In addition to androgen stimulation, PART-1 is also up-regulated by progestins, oestrogens and glucocorticoids. We further studied the expression of PART-1 in 27 paired (from the same patient) cancerous and non-cancerous prostatic tissues, with qualitative and quantitative RT-PCR (LightCycler technology), in order to examine whether PART-1 is overexpressed or underexpressed in cancer. Our results indicated that PART-1 is more frequently overexpressed in the cancerous prostatic tissue. We conclude that this gene is overexpressed in prostate cancer and may represent a novel prostate cancer tumour marker.

Aged↗

A mutant plasma membrane ATPase, Pma1-10, is defective in stability at the yeast cell surface.

Pma1 is a plasma membrane H(+)-ATPase whose activity at the cell surface is essential for cell viability. In this paper we describe a temperature-sensitive pma1 allele, pma1-10 (with two point mutations in the first cytoplasmic loop of Pma1), in which the newly synthesized mutant protein fails to remain stable at the cell surface at 37 degrees C. Instead, Pma1-10 appears to undergo internalization for vacuolar degradation in a manner dependent on End4, Vps27, Doa4, and Pep4. By contrast with wild-type Pma1, mutant Pma1-10 is hypophosphorylated and fails to associate with a Triton-insoluble fraction at 37 degrees C, suggesting failure to enter lipid rafts. Kinetic analysis reveals that, at the permissive temperature, newly synthesized Pma1-10 acquires Triton-insolubility before becoming stabilized. We suggest that phosphorylation and lipid raft association may play important roles in maintaining protein stability at the plasma membrane.

Cell Membrane↗

Intracellular retention of newly synthesized insulin in yeast is caused by endoproteolytic processing in the Golgi complex.

An insulin-containing fusion protein (ICFP, encoding the yeast prepro-alpha factor leader peptide fused via a lysine-arginine cleavage site to a single chain insulin) has been expressed in Saccharomyces cerevisiae where it is inefficiently secreted. Single gene disruptions have been identified that cause enhanced immunoreactive insulin secretion (eis). Five out of six eis mutants prove to be vacuolar protein sorting (vps)8, vps35, vps13, vps4, and vps36, which affect Golgi<-->endosome trafficking. Indeed, in wild-type yeast insulin is ultimately delivered to the vacuole, whereas vps mutants secrete primarily unprocessed ICFP. Disruption of KEX2, which blocks intracellular processing to insulin, quantitatively reroutes ICFP to the cell surface, whereas loss of the Vps10p sorting receptor is without effect. Secretion of unprocessed ICFP is not based on a dominant secretion signal in the alpha-leader peptide. Although insulin sorting mediated by Kex2p is saturable, Kex2p functions not as a sorting receptor but as a protease: replacement of Kex2p by truncated secretory Kex2p (which travels from Golgi to cell surface) still causes endoproteolytic processing and intracellular insulin retention. Endoproteolysis promotes a change in insulin's biophysical properties. B5His residues normally participate in multimeric insulin packing; a point mutation at this position permits ICFP processing but causes the majority of processed insulin to be secreted. The data argue that multimeric assembly consequent to endoproteolytic maturation regulates insulin sorting in the secretory pathway.

Amino Acid Sequence↗

Cloning of a new member of the human kallikrein gene family, KLK14, which is down-regulated in different malignancies.

Kallikreins (KLKs) belong to the serine protease family of proteolytic enzymes. Human pancreatic/renal KLK (KLK1) encodes for an enzyme that is involved in posttranslational processing of polypeptide precursors. The function of the other members of this gene family is currently unknown, but growing evidence suggests that many KLKs are implicated in carcinogenesis. By using the positional candidate approach, we were able to identify a new human KLK-like gene, KLK14 (also known as KLK-L6). This new gene maps to chromosome 19q13.3-q13.4 and is formed of seven exons (two untranslated and five coding exons) and six intervening introns. KLK14 was defined as a KLK gene based on structural and mapping criteria, in relation to other known KLK genes. KLK14 is expressed in a variety of tissues, but the highest levels of KLK14 are found in the central nervous system, including brain, cerebellum, and spinal cord. Our preliminary results show that KLK14 is down-regulated, at the mRNA level, in breast, testicular, prostatic, and ovarian cancer.

Amino Acid Sequence↗

Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions.

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that causes motor, sensory, and cognitive deficits. The present study characterized demyelinated lesions in the cerebral cortex of MS patients. One hundred twelve cortical lesions were identified in 110 tissue blocks from 50 MS patients. Three patterns of cortical demyelination were identified: Type I lesions were contiguous with subcortical white matter lesions; Type II lesions were small, confined to the cortex, and often perivascular; Type III lesions extended from the pial surface to cortical layer 3 or 4. Inflammation and neuronal pathology were studied in tissue from 8 and 7 patients, respectively. Compared to white matter lesions, cortical lesions contained 13 times fewer CD3-positive lymphocytes (195 vs 2,596/mm3 of tissue) and 6 times fewer CD68-positive microglia/macrophages (11,948 vs 67,956/mm3 of tissue). Transected neurites (both axons and dendrites) occurred at a density of 4,119/mm3 in active cortical lesions, 1,107/mm3 in chronic active cortical lesions, 25/mm3 in chronic inactive cortical lesions, 8/mm3 in myelinated MS cortex, and 1/mm3 in control cortex. In active and chronic active cortical lesions, activated microglia closely apposed and ensheathed apical dendrites, neurites, and neuronal perikarya. In addition, apoptotic neurons were increased significantly in demyelinated cortex compared to myelinated cortex. These data support the hypothesis that demyelination, axonal transection, dendritic transection, and apoptotic loss of neurons in the cerebral cortex contribute to neurological dysfunction in MS patients.

Adolescent↗

Cytologically benign endometrial cells in the papanicolaou smears of postmenopausal women.

OBJECTIVE: The objective of this study was to determine the clinical significance of the presence of benign endometrial cells in the Pap smears of postmenopausal women. METHODS: A retrospective analysis of the clinical outcome of 297 postmenopausal women containing benign endometrial cells in their Pap smears was performed. All patients had subsequent endometrial biopsies or routine follow-up for 1-5 years. In addition, Pap smears of 253 of the patients were reviewed with particular reference to the morphology and type of the endometrial cells. Immunohistochemical staining with CD68 was performed in 15 selected cases to determine the origin of the stromal cells. RESULTS: One hundred thirty-two (44%) women had endometrial biopsies while the remaining 165 (56%) were followed up by routine gynecologic examinations and repeat Pap smears. Endometrial lesions were detected in 14 patients of whom only 3 had significant lesions (2 atypical hyperplasias and 1 adenocarcinoma). Review of the Pap smears revealed benign superficial endometrial stromal cells in most cases (73%). Stromal cells showed CD68 positivity indicating a histiocytic origin. Glandular cells were present in 27%, either alone or in association with stromal cells. Statistical analysis revealed that the presence of endometrial glandular cells in Pap smears was associated with five times the likelihood of significant endometrial disease than found in women with normal Pap smears, although sensitivity and positive predictive value were very low (7.14 and 2.94%, respectively). Superficial endometrial stromal cells were not useful in predicting endometrial pathology. CONCLUSION: Significant endometrial lesions were present in 1% of postmenopausal women containing morphologically benign endometrial cells in the Pap smears. In the majority, the endometrial cells were of the superficial stromal type, which were demonstrated immunohistochemically to be histiocytes. The presence of endometrial glandular cells correlated significantly with endometrial pathology. Such an association was not observed in cases with stromal cells only.

Aged↗

Genetic interactions between the ESS1 prolyl-isomerase and the RSP5 ubiquitin ligase reveal opposing effects on RNA polymerase II function.

Transcription of protein-coding genes by RNA polymerase II (pol II) is a highly coordinated process that requires the stepwise association of distinct protein complexes with the C-terminal domain (CTD) of Rpbl, the largest subunit of RNA pol II. Interaction of these complexes with the CTD might be subject to regulation by proteins such as Ess1 and Rsp5. Ess1, a prolyl-isomerase, binds the CTD and is thought to play a positive role in pol II transcription by generating conformational isomers of the CTD. Rsp5, a ubiquitin ligase, binds the CTD and is thought to play a negative role in transcription by mediating Rpbl ubiquitination and degradation. In this paper, we demonstrate that ESS1 and RSP5 interact genetically and that these interactions occur via RPBI. We show that over-expression of RSP5 enhances the growth defect of ess1ts cells and this effect is reversed by introducing extra copies of RPB1. Over-expression of RSP5 also mimics the sensitivity of ess1ts mutant cells to the toxicity of plasmids carrying dominant-negative CTD mutations, whereas mutations in RSP5 suppress this effect. Using a modified two-hybrid assay, we also demonstrate that Essl and Rsp5 compete directly for binding to the CTD. The results suggest a model in which Essl and Rsp5 act opposingly on pol II function to control the level of pol II available for transcription.

Binding, Competitive↗

Functional results two years after laparoscopic rectopexy.

BACKGROUND: Rectopexy is one of the accepted treatment options for full-thickness rectal prolapse, but the details of the technique remain controversial. This unit has adopted a laparoscopic approach as an alternative to open surgery, and has used three techniques: mesh, suture, and resection. This retrospective study compares the long-term outcome. METHODS: From 1993 to 1995, 14 patients underwent a laparoscopic posterior mesh rectopexy. From 1996 to 1999, 34 patients underwent laparoscopic suture rectopexy with (n = 18) or without sigmoid resection (n = 16). RESULTS: There was no postoperative mortality, and morbidity was similar in the three groups, ranging from 11 to 19%. The mean follow-up was 47, 24, and 20 months for mesh, suture, and resection rectopexy, respectively. During follow-up, 1 patient in each group developed mucosal prolapse. There was no difference between the three groups for incontinence rate, which improved in more than 75% of patients who had impaired continence preoperatively. Postoperative constipation was observed in 2 patients (11%) after resection rectopexy, in 10 (62%) after suture rectopexy (P < 0.01 versus resection), and in 9 (64%) after mesh rectopexy (P < 0.01 versus resection). CONCLUSIONS: Our results show that the addition of sigmoid resection to laparoscopic rectopexy is safe and could contribute to reduce the risk of severe constipation after operation. Laparoscopic mesh rectopexy confers no advantage over the sutured technique, which we now use as our fixation method of choice.

Aged↗

Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients.

OBJECTIVE: Comparison of polysomnography (PSG)-derived sleep parameters (total sleep time, sleep efficiency, and number of awakenings) to those derived from actigraphy and subjective questionnaires. BACKGROUND: Actigraphy is commonly used to assist sleep specialists in the diagnosis of various sleep and circadian-rhythm disorders. However, few validation studies incorporate large sample sizes, typical sleep clinic patients, or comparisons with subjective reports of sleep parameters. METHODS: Clinical series with 100 consecutive sleep-disordered patients (69 men, 31 women, mean age of 49+/-14.7 years) at a tertiary sleep disorders center. Sensitivity, specificity, and accuracy measures were obtained from epoch-by-epoch comparison of PSG and actigraphic data. Subjective sleep parameter data were derived from questionnaires given to subjects in the morning following their recording night. RESULTS: We found that total sleep time and sleep efficiency did not significantly differ between PSG data and the combined data obtained from actigraphy and subjective reports. Using a high-threshold (low-wake-sensitivity) actigraphic algorithm, the number of awakenings was not significantly different from those detected by PSG. CONCLUSIONS: We recommend the use of subjective data as an adjunct to actigraphic data in estimating total sleep time and sleep efficiency in sleep-disordered patients, especially those with disorders of excessive somnolence.

Journal Article↗

Transport of opioids from the brain to the periphery by P-glycoprotein: peripheral actions of central drugs.

Many peptides and transmitters found within the brain also have peripheral sites of action. We now demonstrate that the brain releases functionally active neurotransmitters/neuromodulators directly from the brain into the blood through a saturable P-glycoprotein (Pgp) transport system. Downregulating Pgp1 expression with antisense reduced the brain-to-blood transport of morphine, beta-endorphin and other opioids. Lowering Pgp expression significantly enhanced systemic morphine analgesia and prevented tolerance, but diminished the analgesic activity of centrally administered morphine, implying that supraspinal analgesia resulted from a combination of central and peripheral mechanisms activated by morphine transported from the brain to the blood. Similarly, mice with a disruption of the Mdr1a gene were more sensitive to systemic morphine and less sensitive to morphine given centrally. This ability of the Pgp transport system to pump functionally active compounds from the brain to periphery defines a potentially important mechanism for the central nervous system to modulate peripheral systems.

ATP Binding Cassette Transporter, Subfamily B↗