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International Academy of Pathology, Malaysian Division has initiated and run the external quality assurance program for general diagnostic histopathology since the year 2017. This article introduces the educational philosophy of this external quality assurance program and the technicalities in running such a national program. Challenges in ensuring the successful running of this program to gain wide acceptance by histopathology laboratories in Malaysia as well as experience in overcoming these challenges are detailed. This article charts the future direction of this external quality assurance program.

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BACKGROUND: The aim of this study was to investigate the effects of MSCs and MSC-expressing ANGPT1 (MSC-pANGPT1) treatment via aerosolisation in alleviating the asthma-related airway inflammation in the rabbit model. METHODS: Rabbits were sensitised and challenged with both intraperitoneal injection and inhalation of ovalbumin (Ova). MSCs and MSC-pANGPT1 cells were aerosolised into rabbit lungs using the MicroSprayer® Aerosolizer Model IA-1B 48 h after injury. The post mortem was performed 3 days following cell delivery. Histopathological assessments of the lung tissues and inflammatory response were quantitatively scored following treatments. RESULT(S): Administration of aerosolised MSCs and MSC-pANGPT1 were significantly reduced inflammation of the airways (p < 0.001), as reflected by improved of structural changes such as thickness of the basement membrane, epithelium, mucosa and sub-mucosa regions. The airway inflammation score of both treatment groups revealed a significant reduction of inflammation and granulocyte infiltration at the peribronchiale and perivascular regions (p < 0.05). Administration of aerosolised MSCs alone was resulted in significant reduction in the levels of pro-inflammatory genes (IL-4 and TGF-ß) while treatment with aerosolised MSC-pANGPT1 led to further reduction of various pro-inflammatory genes to the base-line values (IL4, TNF, MMP9 and TGF-ß). Treatment with both aerosolised MSCs and MSC-pANGPT1 cells was also alleviated the number of airway inflammatory cells in the bronchoalveolar lavage (BAL) fluid and goblet cell hyperplasia. CONCLUSION(S): Our findings suggest that treatment with MSCs alone attenuated airway inflammation and structural changes of the airway. Treatment with MSC-pANGPT1 provided an additional effect in reducing the expression levels of various pro-inflammatory genes. Both of these treatment enhancing airway repair and therefore may provide a basis for the development of an innovative approach for the treatment and prevention of airway inflammatory diseases.

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No abstract available.

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Aerosol-based cell therapy has emerged as a novel and promising therapeutic strategy for treating lung diseases. The goal of this study was to determine the safety and efficacy of aerosol-based airway epithelial cell (AEC) delivery in the setting of acute lung injury induced by tracheal brushing in rabbit. Twenty-four hours following injury, exogenous rabbit AECs were labelled with bromodeoxyuridine and aerosolized using the MicroSprayer® Aerosolizer into the injured airway. Histopathological assessments of the injury in the trachea and lungs were quantitatively scored (1 and 5 days after cell delivery). The aerosol-based AEC delivery appeared to be a safe procedure, as cellular rejection and complications in the liver and spleen were not detected. Airway injury initiated by tracheal brushing resulted in disruption of the tracheal epithelium as well as morphological damage in the lungs that is consistent with acute lung injury. Lung injury scores were reduced following 5 days after AEC delivery (AEC-treated, 0.25  ± â€…0.06 vs. untreated, 0.53  ± â€…0.05, P  < â€…0.01), and rapid clearance of haemorrhage, proteinaceous debris and hyaline membranes occurred. In the trachea, AEC delivery led to an upsurge in epithelium regeneration and repair. Re-epithelialization was significantly increased 5 days after treatment (AEC-treated, 91.07  ± â€…2.37% vs. untreated, 62.99  ± â€…7.39%, P  < â€…0.01). Our results indicate that AEC delivery helps in the regeneration and repair of the respiratory airway, including the lungs, following acute insults. These findings suggest that aerosol-based AEC delivery can be a valuable tool for future therapy to treat acute lung injury. Copyright © 2017 John Wiley & Sons, Ltd.

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Danshen and Gegen are two commonly used Chinese herbal medicines for treatment of cardiovascular diseases. The aim of the present study was to elucidate the combination effects of these two herbs on cerebral vascular tone and their underlying mechanisms of actions. Basilar artery rings were obtained from rats and precontracted with U46619. Cumulative administrations of aqueous extracts of Danshen, Gegen, or the two herbs combined (DG; ratio 7:3) produced concentration-dependent relaxation of the artery rings. Statistical analysis on these findings produced a combination index (CI) of 1.041 at ED50, which indicates the two herbs produced additive vasodilator effects when used as a combined decoction. Removal of the endothelium had no effect on the vasodilator properties of Danshen, Gegen, and DG. However, their maximum effects (Imax) were significantly blunted by a KATP channel inhibitor glibenclamide, a non-selective K(+) channel inhibitor tetraethylammonium (TEA), and by a combination of K(+) channel inhibitors (glibenclamide+TEA+iberiotoxin+4-aminopyridine+barium chloride). In addition, Danshen, Gegen, and DG produced augmentation of KATP currents and inhibited Ca(2+) influx in vascular smooth muscle cells isolated from rat basilar arteries. Furthermore, these agents inhibited CaCl2-induced contraction in the artery rings. In conclusion, the present study showed that Danshen and Gegen produced additive vasodilator effects on rat cerebral basilar arteries. These effects were independent of endothelium-derived relaxant factors (EDRF), but required the opening of KATP channels and inhibition of Ca(2+) influx in the vascular smooth muscle cells. It is suspected that the cerebral vasodilator effects of Danshen and Gegen produced either on their own or in combination, can help patients with obstructive cerebrovascular diseases.

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We have compared a simple four-strand flexor tendon repair, the single cross-stitch locked repair using a double-stranded suture (dsSCL) against two other four-strand repairs: the Pennington modified Kessler with double-stranded suture (dsPMK); and the cruciate cross-stitch locked repair with single-stranded suture (Modified Sandow). Thirty fresh frozen cadaveric flexor digitorum profundus tendons were transected and repaired with one of the core repair techniques using identical suture material and reinforced with identical peripheral sutures. Bulking at the repair site and tendon-suture junctions was measured. The tendons were subjected to linear load-to-failure testing. Results showed no significant difference in ultimate tensile strength between the Modified Sandow (36.8 N) and dsSCL (32.6 N) whereas the dsPMK was significantly weaker (26.8 N). There were no significant differences in 2 mm gap force, stiffness or bulk between the three repairs. We concluded that the simpler dsSCL repair is comparable to the modified Sandow repair in tensile strength, stiffness and bulking.

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ETHNOPHARMACOLOGICAL RELEVANCE: Gegen (root of Pueraria lobata) is used in traditional Chinese medicine for treatment of cardiovascular diseases. In this study, the relaxant actions of three of its isoflavonoids; puerarin, daidzein, and daidzin, were investigated on rat-isolated cerebral basilar artery. MATERIALS AND METHODS: Rat basilar artery rings were precontracted with 100 nM U46619. Involvement of endothelium-dependent mechanisms was investigated by mechanical removal of the endothelium and inhibitors of nitric oxide synthase (NOS) and cyclooxygenase (COX) enzymes. Adenylyl cyclase- and guanylyl cyclase-dependent pathways were investigated using their respective inhibitors 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536) and 1H-[1,2,4]oxadiazolo [4,3-[alpha]]-quinoxalin-1-one (ODQ). K(+) channels were investigated by pretreatment of the artery rings with various K(+) channel inhibitors, and Ca(2+) channels were investigated in artery rings incubated with Ca(2+)-free buffer and primed with 100 nM U46619 for 5 min prior to adding CaCl(2) to elicit contraction. RESULTS: Puerarin, daidzein, and daidzin produced concentration-dependent relaxation of the artery rings with concentration that produced 50% inhibition (IC(50)) of 304 ± 49 µM, 20 ± 7 µM, and 140 ± 21 µM, respectively. Removal of the endothelium produced no change on their vasorelaxant responses except the maximum response (I(max)) to puerarin was inhibited by 28%. The NOS inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 100 µM) also produced 45% inhibition on the puerarin-induced vasorelaxant response, but not the COX inhibitor flurbiprofen (10 µM). SQ22536 (100 µM) and ODQ (100µM) did not affect the vasodilator responses to puerarin, daidzein and daidzin, but glibenclamide (1µM), tetraethylammonium (TEA, 100mM) or a combination of K(+) channel inhibitors (100nM iberiotoxin+1mM 4-aminopyridine+100 µM barium chloride+1 µM glibenclamide+100mM TEA) reduced their I(max). The contractile response to CaCl(2) was attenuated by 61% and 34% in the presence of daidzein and daidzin, respectively, whereas, puerarin did not significantly affect the contraction. CONCLUSIONS: The vasorelaxant action of daidzein and daidzin involved opening of K(+) channels and inhibition of Ca(2+) influx in the vascular smooth muscle cells. There is no evidence supporting involvement of endothelium-derived relaxing factors (EDRFs) in their actions. In contrast, puerarin produced vasodilatation via an endothelium-dependent mechanism involving nitric oxide production and an endothelium-independent pathway mediated by the opening of K(+) channels. The cerebral vasodilator activities of all these three isoflavonoids may be beneficial to patients with obstructive cerebrovascular diseases.

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While doctor-engineer collaborations are imperative for the advancement of medical technology to improve patient care, these partnerships are often fraught with poorly understood barriers, including differences in knowledge base, conflicts over authorship and difficulty in applying deterministic solutions to biological data. As there is scarce literature on the dynamics of doctor-engineer collaborations, this essay discusses these hurdles and proposes practical ways to overcome, or at least attenuate them.

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AIM OF THE STUDY: Danshen (root of Salvia miltiorrhiza) and gegen (root of Pueraria lobata) are two herbs used in traditional Chinese medicine, most commonly for their putative cardioprotective and anti-atherosclerotic effects. In this study, the actions of a danshen and gegen formulation (DG; ratio 7:3) were investigated on rat-isolated cerebral basilar artery. MATERIALS AND METHODS: Rat basilar artery rings were precontracted with 100 nM U46619. Involvement of endothelium-dependent mechanisms was investigated by mechanical removal of the endothelium; K(+) channels were investigated by pretreatment of the artery rings with various K(+) channel inhibitors, and Ca(2+) channels were investigated in artery rings incubated with Ca(2+)-free buffer and primed with 100 nM U46619 for 5 min prior to adding CaCl(2) to elicit contraction. RESULTS: DG produced concentration-dependent relaxation of the artery rings with an IC(50) of 895±121 µg/ml. Mechanical removal of the endothelium or pretreatment with the BK(Ca) channel inhibitor iberiotoxin (100 nM), the K(V) channel inhibitor 4-aminopyridine (1 mM), or the K(IR) channel inhibitor barium chloride (100 µM), all had no effect on the DG-induced response (P>0.05 for all). However, pretreatment with the K(ATP) channel inhibitor glibenclamide (1 µM), the non-selective K(+) channel inhibitor tetraethylammonium (TEA, 100 mM), or a combination of all the K(+) channel inhibitors (iberiotoxin+4-aminopyrindine+barium chloride+glibenclamide+TEA) produced significant inhibition on the DG-induced response (P<0.01 for all); its maximum vasorelaxant effect (Imax) was reduced by 37, 24, and 30%, respectively. Preincubation of the artery rings with DG for 10 min produced concentration-dependent (1, 3 and 7 mg/ml) and total inhibition on the CaCl(2)-induced vasoconstriction. CONCLUSIONS: These findings suggest the vasorelaxant effect of DG on rat basilar artery is independent of endothelium-derived mediators, whereas, inhibition of Ca(2+) influx in the vascular smooth muscle cells is important, and a minor component is mediated by the opening of K(ATP) channels. DG could be a useful cerebroprotective agent in some patients with occlusive cerebrovascular disease.

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This cadaveric study evaluates the margin of safety and technical efficacy of mini open carpal tunnel release performed using Knifelight (Stryker Instruments) through a transverse 1 cm wrist incision. A single investigator released 32 wrists in 17 cadavers. The wrists were then explored to assess the completeness of release and damage to vital structures including the superficial palmar arch, palmar cutaneous branch and recurrent branch of the median nerve. All the releases were complete and no injury to the median nerve and other structures were observed. The mean distance of the recurrent motor branch to the ligamentous divisions was 5.7 +/- 2.4 mm, superficial palmar arch was 8.7 +/- 3.1 mm and palmar cutaneous branch to the ligamentous division was 7.2 +/- 2.4 mm. The mean length of the transverse carpal ligament was 29.3 +/- 3.7 mm. Guyon's canal was preserved in all cases.

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OBJECTIVE: Sensory symptoms within the median nerve distribution are a primary clinical diagnostic criterion for the diagnosis of carpal tunnel syndrome (CTS). However, the distribution of the sensory symptoms in CTS varies from patient to patient. This study identifies the clinical and electrophysiological findings that correlate with the distribution of sensory symptoms in an Asian population with CTS. METHODS: In a prospective study of 105 patients with electrophysiologically confirmed CTS, clinical and educational data were correlated with sensory symptom distribution. RESULTS: Median nerve distribution was strongly associated with more severe nerve conduction abnormality, male gender, and relief by movement. Patients with a complete median sensory distribution had more electrophysiological abnormality than those with an incomplete median distribution. Extra-median distribution was associated with the least nerve conduction abnormality. Educational qualification, age, symptom duration and body mass index were not associated with the pattern of sensory symptoms. CONCLUSIONS: In carpal tunnel syndrome, sensory symptom distribution is strongly dependant on the degree of electrophysiological median nerve damage. Median nerve sensory distribution is associated with severe nerve damage. SIGNIFICANCE: This study provides clinicians with a simple clinical rule for assigning the degree of median nerve damage in patients with CTS based on sensory distribution patterns.

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OBJECTIVE: Despite the increase in colorectal cancer (CRC) incidence among Chinese in Asia, there are no data on predictors of CRC screening uptake in this population. This study investigated how knowledge and perceptions about CRC correlated with screening behavior in Singaporean-Chinese. METHODS: A community-based cross-sectional study was carried out on Singaporean-Chinese at least 50 years old in Queenstown Estate, Singapore between 1/1/2006 and 1/2/2006. A questionnaire administered via face-to-face interviews elicited knowledge, perceptions and screening behavior of subjects. RESULTS: The response rate was 72.4%, with 514 completed responses. Expense was the commonest perceived barrier to screening (56.6% agreed), unlike for other populations. Social influence is important, with 67.5% agreeing to the statement "I would go for CRC screening if my family wanted me to". After excluding confounders, Chinese who had been for fecal occult blood test (FOBT) screening had higher knowledge score (p<0.001), lower perceived severity (p<0.01), were more likely to have been influenced by their family/friends to go for screening (p=0.04) and to have attended screening tests for other diseases (p<0.001). CONCLUSION: FOBT screening uptake is associated with specific areas of knowledge and perception among Singaporean-Chinese. To increase screening uptake within Chinese populations, clinicians should consider these factors in their approach to patients.

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PURPOSE: To compare the results of Achilles tendon repair using a standard open procedure or a minimally invasive technique using a double-ended needle, and to determine whether the latter technique reduces the incidence of sural nerve injury and soft-tissue complications. METHODS: Between the period February 1995 and September 2000 inclusive, 68 consecutive patients with acute Achilles tendon rupture underwent surgical repair in our hospitals. A standard open repair was performed on 43 patients (mean age 36 years and range 17-74 years, 30 males), while 25 patients (mean age 34 years and range 19-68 years, 17 males) elected to undergo the minimally invasive procedure involving a double-ended needle. Postoperative protocols were identical for the 2 groups. Patients were assessed for re-rupture, calf muscle strength, calf atrophy, wound healing, and ability to return to pre-injury activity. The mean follow-up period was 65.5 (range, 34-90) months. RESULTS: One late re-rupture and one sural nerve injury occurred in the standard open repair group. No rerupture or sural nerve injury occurred in those having minimally invasive surgery, they also reported fewer complications related to wound healing and a shorter hospital stay. Calf atrophy was also significantly less in this group (p<0.05). CONCLUSION: This double-ended needle repair technique is simple and reproducible. The needle is easy to make using a standard mini Steinmann pin with minimal cost. Combined with appropriate rehabilitation, the technique achieves good results and is associated with a low morbidity and complications.

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The conventional upper arm tourniquet used for hand and wrist operations may cause significant discomfort to patient when the procedure is performed under local anaesthesia. Forearm tourniquet causes less muscle ischeamia and pain. The discomfort experienced while using a forearm and upper arm tourniquet was assessed in 96 healthy subjects. Tourniquet placed on both sides was inflated sequentially to 250mmhg for five minutes on different hand. The discomfort level was assessed using a small visual analogue scale and complications were recorded. In the upper arm tourniquet, 24.9% had mild, 60.5% had moderate and 14.6% had severe pain whereas with forearm tourniquet, 99% had mild pain and only 1% had moderate pain. Seventy-nine percent of the subjects tested with forearm tourniquet had no discomfort at all. The average discomfort level for upper arm and forearm tourniquet was 4.72 and 0.39 respectively, which is statistically significant. Complications that were observed only in upper arm tourniquet included prolonged tingling, burning sensation and discomfort and stiffness of the upper limb. We concluded that forearm tourniquet was safe and well tolerated and should be used more often when indicated.

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Bone defect following en bloc resection of primary bone tumor around the knee can be reconstructed by allograft or prothesis or combination of both. Resection-arthrodesis is an alternative option for young vigorous patients facing circumstances of financial constrain or limited supply of allograft. This study was undertaken to determine the outcome and complications associated with resection-arthrodesis of 22 primary bone tumors (13 giant cell tumors and 9 osteosarcomas) around the knee treated between 1990 and 2003 at the University Malaya Medical Center. The mean follow-up was 6 years (range 1-13 years). hree patients with osteosarcoma died of lung metastasis, 3 required above knee amputation and 2 defaulted follow-up. Local complications of the procedure include infection in 8 cases (36.4%), non-union 7 (31.8%) and mal-union. Of 14 patients who returned for final evaluation, 79.8% had satisfactory outcomes according to the Musculoskeletal Tumor Society grading system. In conclusion, resection-arthrodesis of the knee is a viable treatment option for selected patients with primary bone tumor around the knee, and good functional outcome can be expected in the presence of short-term local complications.

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PURPOSE: To review cases of giant cell tumour of bone or osteoclastoma managed at the University Malaya Medical Center, University of Malaya, Kuala Lumpur, from January 1990 to December 1999. METHODS: Medical records of all patients with musculoskeletal tumours were reviewed. Demographic data, clinical presentation, surgical management, and clinical outcomes were reviewed retrospectively. RESULTS: Most of the 31 patients who were treated for giant cell tumour of bone presented late on the basis of the duration of their symptoms and radiological features. Five of the patients had been referred for local recurrences. 26 patients were treated for primary tumours: 18 needed wide excision, 7 curettage, and one amputation. The joint could not be preserved and arthrodesis was performed for 11 patients. Three (12%) of the 26 patients had local recurrence during a mean follow-up of 60 months, including one (6%) who had recurrence after wide excision and 2 (29%) after curettage. Pulmonary metastasis was noted in 4 cases, 2 of which were confirmed histologically. CONCLUSION: Even in an advanced stage of disease, good clinical outcomes can be achieved with adequate excision and appropriate reconstruction. For lesions around the knee, autologous rotational grafting is a good alternative method of reconstruction.

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