Clinical Audit on Chronic Obstructive Pulmonary Disease (COPD) Management in Primary Care: A Quality Improvement Project from Hong Kong.

Objective: To enhance the quality of COPD management in primary care via a two-phase clinical audit in Hong Kong. Methods: COPD patients aged 40 or above and had attended any of the 73 public primary care clinics under the Hospital Authority of Hong Kong (HAHK) for follow up (FU) during the audit period were included. Performance of six evidence-based audit criteria on COPD care was reviewed in phase 1 from 1st April 2017 to 31st March 2018. Service gaps were identified and a series of quality improvement strategies were executed in the one-year implementation phase. The outcome of the service enhancement was assessed in phase 2 from 1st April 2019 to 31st March 2020. Student's t-test and the chi-square test were used to examine the statistically significant differences between the two phases. Results: Totally 10,385 COPD cases were identified in phase 1, the majority were male (87.7%) and the mean age was 75.3±9.9 years. Among the 3102 active smokers, 1788 (57.6%) were referred to receive the smoking cessation counselling and 1578 (50.9%) actually attended it. A total of 4866 cases (46.9%) received seasonal influenza vaccine (SIV) and 4227 cases (40.7%) received pneumococcal vaccine (PCV). A total of 1983 patients (19.1%) had spirometry test done before and 1327 patients (12.8%) had history of hospital admission due to acute exacerbation of COPD (AECOPD). After the proactive implementation phase, performance on all criteria was significantly improved in phase 2, with a marked increase in the SIV and PCV uptake rate and spirometry performance rate. Most importantly, a significant reduction in AECOPD rate leading to hospital admission had been achieved (9.6%, P<0.00001). Conclusion: COPD care at all public primary care clinics of HAHK had been significantly improved for all audit criteria via the systematic team approach, which, in turn, reduced the hospital admission rate and helped relieve the burden of the health care system.

Percutaneous transcatheter aortic valve replacement: first transapical implant in Asia.

Percutaneous transcatheter implantation of the aortic valve has been demonstrated as an alternative to open heart surgery in high-risk patients with symptomatic severe aortic stenosis (AS) who are not suitable for open surgery. The majority of these new devices are delivered via the transfemoral approach. However, due to the current size of delivery sheaths, the small and tortuous iliofemoral anatomy makes this approach challenging. The transapical approach provides a viable option for this patient subgroup. The first-in-Asia transcatheter aortic valve implantation via the transapical route is described. A 79-year-old Chinese woman with symptomatic severe AS and peripheral arterial disease, who was at high surgical risk, was successfully treated, and had good functional and haemodynamic results at the three-month follow-up.

Percutaneous transcatheter aortic valve replacement: first transfemoral implant in Asia.

Surgical aortic valve replacement (AVR) is the standard of care for patients with symptomatic severe aortic stenosis (AS), providing relief of symptoms and prolonging survival. However, many patients are either denied or not offered surgery due to high surgical risk or non-operability for open AVR. The technology of percutaneous aortic valve implantation emerged in 2002, and has since evolved rapidly with satisfactory results. Currently, almost all the procedures are performed predominantly in Europe and North America. The first-in-Asia percutaneous transcatheter aortic valve implantation via the transfemoral route is described. A 77-year-old man with symptomatic severe AS and at high surgical risk was successfully treated, with sustained clinical improvement and satisfactory haemodynamic results at 30-day follow-up.

IL-1beta induction of RANTES (regulated upon activation, normal T cell expressed and secreted) chemokine gene expression in endometriotic stromal cells depends on a nuclear factor-kappaB site in the proximal promoter.

A complex network of cytokines mediates immunoregulatory responses in the pathogenesis of endometriosis. RANTES (regulated upon activation, normal T cell expressed and secreted) is a chemoattractant for monocytes and T cells. Endometriotic lesions express RANTES, and its concentration in peritoneal fluid correlates with the severity of endometriosis. We investigated the influence of IL-1beta, a potent macrophage cytokine, on RANTES production in endometriotic stromal cells and determined the region of the RANTES promoter responsible for IL-1beta action. RANTES mRNA was induced 5-fold in endometriotic stromal cells, and the conditioned medium RANTES protein concentrations were 12-fold higher in IL-1beta-treated endometriotic stromal cells vs. untreated controls (P < 0.05). IL-1beta activated the full-length (-940 bp) RANTES promoter as well as a truncated 456-bp 5'-flanking construct by 2-fold. Mutagenesis of a nuclear factor-kappaB response element at -30 bp abolished the IL-1beta effect, whereas mutation of a nearby TNF response element did not affect the IL-1beta induction. An IL-1beta time-course Western assay revealed a rapid diminution of IkappaB (endogenous inhibitor of nuclear factor-kappaB) in endometriotic stromal cells. Overexpression of IkappaB in endometriotic stromal cells inhibited the IL-1beta response of the RANTES gene promoter. Transcription of RANTES mRNA is up-regulated by IL-1beta via a nuclear factor-kappaB response element in the proximal RANTES gene promoter. These results demonstrate a feed-forward regulatory loop in the pathogenesis of endometriosis by which IL-1beta produced from activated macrophages can lead to further macrophage recruitment via RANTES production in endometriotic stromal cells.

Optimum tensioning position for extensor indicis to extensor pollicis longus transfer.

This study evaluates various wrist and thumb positions for tensioning the extensor indicis proprius when transferred to the extensor pollicis longus tendon to determine which positions provide optimum passive range of flexion and extension of the thumb. In five adult cadaver upper limbs, transfer of the extensor indicis proprius to the extensor pollicis longus was simulated. The limbs were fixed with the elbow in 90 degrees flexion and the forearm and wrist in neutral. Surface bone markers were digitized to determine the thumb and wrist positions in three-dimensional space and their intersegmental joint angles. Twelve combinations of thumb (the interphalangeal and metacarpophalangeal joints) and wrist positions for tensioning were tested. A fixed tension of 80 N was applied to the tendon ends for each of the tensioning positions and during the transfer to ensure that the tendon remained taut. A wrist tenodesis effect was used subsequently to assess the passive range of thumb motion as an indicator of the outcome of the transfer. The results showed that the better tensioning position was with the thumb fully extended and the wrist in neutral. In six patients in whom an extensor indicis proprius to extensor pollicis longus transfer was done, the tendons were tensioned with the thumb in full extension and the wrist in neutral. A prospective review and functional assessment at an average of 18.6 months' followup was done. No significant differences between the surgically treated and normal thumbs were seen for the Jebsen Taylor, 9-peg, and grip and pinch strength tests. The study suggests that in an extensor indicis proprius to extensor pollicis longus transfer, tensioning of the tendons with the thumb in full extension and the wrist in neutral gives good thumb flexion and extension range.

Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1beta.

Activated peritoneal macrophages are associated with endometriosis and may play a central role in its aetiology by releasing interleukin-1beta (IL-1beta) in response to refluxed endometrium. Pari passu with the establishment of endometriotic implants is the development of a vascular supply. In this study we investigated the angiogenic properties of two endometrial proteins, vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6), and assessed their production in response to IL-1beta stimulation in human stromal cells isolated from normal endometrium (NE) and endometriotic lesions (EI). Proliferation of bovine brain capillary endothelial cells (BBCE) with a [(3)H]-thymidine incorporation assay was observed when VEGF (2.1 +/- 0.2-fold; P < 0.05) or VEGF and IL-6 (1.8 +/- 0.1-fold; P < 0.05) were added in vitro, relative to saline-treated control cultures. Northern blot analysis showed induction of VEGF mRNA (2.6-fold; P < 0.05) and IL-6 mRNA (6.3-fold; P < 0.05) transcripts in EI cells, but not NE cells, exposed to IL-1beta. A similar induction was seen with VEGF and IL-6 protein secretion in the responsive EI cells. Reverse transcription-polymerase chain reaction (RT-PCR) for the IL-1 receptor type I (IL-1 RI) indicated that the differential effects of IL-1beta on NE and EI cells was associated with 2.4 +/- 0.1-fold more receptor mRNA in EI versus NE cells. We propose that the ability of IL-1beta to activate an angiogenic phenotype in EI stromal cells but not in NE cells, is mediated by the IL-1 RI.

Reconstruction of a supinated hypoplastic thumb with combined Huber transfer and derotation osteotomy: a case report.

The use of the abductor digiti minimi transfer to restore opposition in patients with hypoplasia of the thumb has been widely described in the literature. It has been found to be effective in restoring abduction, but less so in restoring the rotational component of opposition. In cases where there is concomitant supination of the thumb, abductor digiti minimi transfer alone would not result in a good pinch as the thumb pulp is rotated away from the opposing finger. We present a case of a 6-year-old girl with a hypoplastic supinated left thumb which resembled a digit. There was also hypoplasia of the index finger. The hand had poor function as a result of lack of opposition of the thumb. The thumb function was restored by combining a derotational osteotomy (80 degrees) with the abductor digiti minimi transfer originally described by Huber. Patient was able to hold small object using key pinch and she could pinch with opposition of the thumb pulp to the middle, ring and little finger pulps when reviewed 2 years post-surgery.

Synaptogenesis of mossy fibers induced by spatial water maze overtraining.

Synaptic plasticity has been proposed as a mechanism underlying learning and memory. Synaptic reorganization of hippocampal mossy fibers has been observed after experimentally induced epilepsy, and after brief high-frequency activation inducing long-term potentiation. Furthermore, it has been suggested that synaptic changes in the hippocampus may occur after spatial learning. In this study, by using a zinc-detecting histologic technique (Timm), we demonstrate a significant increase of mossy fiber terminals in the CA3 stratum oriens region induced by training rats during 3 days in a spatial Morris water maze. In contrast, animals trained for only 1 day and animals that were just allowed to swim or were overtrained in a stress-motivated inhibitory avoidance task did not show increments of mossy fiber terminals in the stratum oriens. Electron microscopy confirmed that synaptic density of mossy fiber terminals in the stratum oriens increases significantly in water maze overtrained animals compared with the swimming control animals. Taken together, these results suggest that overtraining in a spatial learning task induces mossy fiber synaptogenesis that could be involved in the mechanisms underlying long-term memory storage. Hippocampus 1999;9:631-636.

The NMDA receptor antagonist CPP impairs conditioned taste aversion and insular cortex long-term potentiation in vivo.

It has been proposed that long-term potentiation (LTP) a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC) a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl-d-aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonist CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid) disrupts the acquisition of conditioned taste aversion, as well as, the IC-LTP induction in vivo. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA dependent neocortical LTP, constitute a possible mechanism for the learning related functions performed by the IC.

In vivo long-term potentiation in the insular cortex: NMDA receptor dependence.

It has been demonstrated that the insular cortex (IC) plays an important role in the acquisition and storage of different aversive motivated learning tasks like conditioned taste aversion, spatial maze and inhibitory avoidance. It is of particular interest to investigate whether activity-dependent modification of synaptic efficacy, a presumptive mechanism for learning and memory, is present in this cortical region. Here, we address this issue by examining the induction of synaptic plasticity, long-term potentiation (LTP) in in vivo preparations. The results showed that high frequency stimulation of the basolateral amygdaloid nucleus (Bla) induced LTP in the IC. The LTP induced by tetanus was blocked by application of the N-methyl-D-aspartate (NMDA) receptor antagonists CPP and MK-801, indicating that NMDA receptors were responsible for its induction. These results suggest that in vivo tetanus induced LTP of the Bla-IC projection is a possible mechanism for the memory-related functions performed by the IC.

Human umbilical vessels and cultured umbilical vein endothelial and smooth muscle cells lack detectable protein and mRNA encoding estrogen receptors.

OBJECTIVE: To identify and characterize estrogen receptors in human umbilical vascular tissues and in cultured cells derived from the human umbilical vein. METHODS: Human umbilical vein endothelial (HUVE) and human umbilical vein smooth muscle (HUVSM) cells were isolated. Immunohistochemical, radioligand binding. Western immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR) methods were used to detect estrogen receptors in vascular tissues and in cells derived from the umbilical cord. RESULTS: Estrogen receptor protein was not detected in either umbilical vessel tissue or in isolated HUVE or HUVSM cells. Messenger RNAs for the classic estrogen receptor (alpha) and estrogen receptor beta isoforms also were undetectable by RT-PCR. CONCLUSION: These findings suggest that the effects of estradiol observed in this widely used vascular model are mediated by very low concentrations of receptors that evade standard methods of detection. Alternatively, this steroid may affect umbilical vascular cells through mechanisms that do not involve the classic genomic estrogen-receptor pathway.

Tissue distribution of estrogen receptors alpha (ER-alpha) and beta (ER-beta) mRNA in the midgestational human fetus.

We compared the expression profiles of the mRNAs of both estrogen receptors, ER-alpha and the recently cloned ER-beta, in the midgestational human fetus by semiquantitative RT-PCR. ER-alpha was most abundant in the uterus, and smaller quantities were detected in the ovary, testis, skin and gut. High amounts of ER-beta mRNA were present in fetal ovaries, testes, adrenals and spleen. In these tissues, the levels of ER-beta mRNA were higher than ER-alpha. In the uterus, however, ER-alpha mRNA was more abundant, and ER-beta mRNA was expressed only moderately. ER-beta mRNA was present at moderate to low levels in the thymus, pituitary gland, skin, lung, kidney and brain cortex. In the course of our work, using the ER-beta primers on genomic DNA, an intron of 2468 bp in length, located between nt 222 and 223 in the A/B domain of ER-beta cDNA, was detected, cloned and sequenced. The study shows that the expression profile of the two ERs is different, and ER-beta is expressed in a variety of tissues during human fetal development, suggesting different, organ-specific roles for the two receptors.

Immunolocalization and regulation of the chemokine RANTES in human endometrial and endometriosis tissues and cells.

Retrograde menstruation is postulated as the initiating event in the histogenesis of endometriosis; however, subsequent steps in the pathogenesis of this common disorder remain poorly characterized. The ip accumulation of activated leukocytes and the infiltration of endometriosis lesions by macrophages and T cells are cytological markers of the inflammatory nature of this syndrome. The apparent recruitment of these leukocytes prompted us to search for chemokine expression by endometriosis cells. We reported previously that pelvic fluid RANTES (regulated upon activation, normal T cell expressed and secreted) concentrations correlated with the stage of endometriosis. In the current study, RANTES messenger ribonucleic acid (mRNA) was identified in normal endometrium and endometriosis lesions, and techniques were developed to localize RANTES protein within these tissues. Using isolated endometrial and endometriosis cell cultures, we demonstrated that RANTES mRNA and protein can be induced by the proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma in endometrial stromal, but not in epithelial or adenocarcinoma cells. Immunocytochemical studies confirmed the biochemical findings. Metabolic labeling experiments verified that nascent RANTES secreted by cytokine-stimulated endometriosis stromal cells was the mature, 8-kDa protein predicted by the mRNA encoding this chemokine. The results indicate that RANTES is a normal constituent of the eutopic endometrium. We propose that secretion of RANTES by ectopic endometriosis implants provides a mechanism for peritoneal leukocyte recruitment.

Human endothelial cell morphology and autacoid expression.

Human umbilical vein endothelial (HUVE) cells plated on plastic or gelatin-coated dishes grow as a "cobblestone" monolayer. By contrast, endothelial cells cultured on a complex matrix (e.g., Matrigel) form three-dimensional, capillary-like structures. In the current study, we verified the capillary phenotype of the latter structures and asked whether the morphological changes induced by extracellular matrix also affect human endothelial gene expression and function in vitro. Concentrations of cellular fibronectin, prostacyclin, and endothelin-1 were measured in the conditioned media by enzyme-linked immunosorbent and radioimmunoassays. Steady-state concentrations of HUVE mRNA were estimated by reverse transcription-polymerase chain reaction and quantified by Northern analyses to assess fibronectin and endothelin-1 gene expression. We found that the subjacent extracellular matrix affects the morphology, proliferation, and differentiation of HUVE cells in vitro. Cells cultured on gelatin were more mitotically active, expressed significantly less cellular fibronectin, made similar amounts of prostacyclin, and secreted significantly more endothelin-1 compared with the same cells grown on a Matrigel substrate.

Extraplacental human fetal tissues express mRNA transcripts encoding the human chorionic gonadotropin-beta subunit protein.

The glycoprotein hormone human chorionic gonadotropin (hCG) is synthesized in large quantities by the developing placenta, reaching peak concentrations in maternal blood during the late first trimester and early midtrimester of pregnancy. In general it is believed that the alpha-subunit of this dimeric hormone is expressed in pituitary gonadotropes, thyrotropes, and trophoblasts, while the beta-subunit is expressed exclusively by trophoblasts. Studies from our laboratory and other laboratories have shown that some midtrimester human fetal tissues, in addition to the placenta, can synthesize proteins that appear to be very similar to the beta-subunit of hCG. To define precisely the nature of this putative hCG-beta-subunit in extraplacental fetal tissues, we have examined the mRNA from a variety of human fetal and adult tissues using nucleic acid hybridization and reverse transcription-polymerase chain reaction (PCR) methods. Our results demonstrate that midtrimester fetal kidney and adrenal tissues contain hCG-beta mRNA transcripts at concentrations comparable to that of placenta, while fetal lung, brain, muscle, and adult adrenal contain only trace to undetectable levels of hCG-beta mRNA. By restriction endonuclease mapping of PCR fragments from fetal tissue cDNAs, we show that the hCG-beta transcript expressed in midtrimester human fetal organs is a bone fide copy of hCG-beta gene No. 5 of the beta-subunit gene family located on chromosome 19.