Intrarectal administration of mCRAMP-encoding plasmid reverses exacerbated colitis in Cnlp(-/-) mice.

Cathelicidin is a pleiotropic host defense peptide secreted by epithelial and immune cells. Whether endogenous cathelicidin is protective against ulcerative colitis, however, is unclear. Here we sought to delineate the role of endogenous murine cathelicidin (mCRAMP) and the therapeutic efficacy of intrarectal administration of mCRAMP-encoding plasmid in ulcerative colitis using dextran sulfate sodium (DSS)-challenged cathelicidin-knockout (Cnlp(-/-)) mice as a model. Cnlp(-/-) mice had more severe symptoms and mucosal disruption than the wild-type mice in response to DSS challenge. The tissue levels of interleukin-1ß and tumor necrosis factor-α, myeloperoxidase activity and the number of apoptotic cells were increased in the colon of DSS-challenged Cnlp(-/-) mice. Moreover, mucus secretion and mucin gene expression were impaired in Cnlp(-/-) mice. All these abnormalities were reversed by the intrarectal administration of mCRAMP or mCRAMP-encoding plasmid. Taken together, endogenous cathelicidin may protect against ulcerative colitis through modulation of inflammation and mucus secretion.

Management of knee osteoarthritis presenting with tibial stress fractures.

Stress fractures of the tibia secondary to tibial deformities from osteoarthritis are rare, and may be difficult to manage. We treated two patients with stress fractures of the proximal tibial diaphyses over a period of two years. Both patients had osteoarthritis of the knee; one with genu valgus deformity and the other, genu varus deformity. The former patient also had a distal tibial fracture and had previously undergone open reduction and internal fixation. The stress fractures of both the patients had been treated conservatively by nonoperative means, but their fractures failed to unite. They then underwent a modular total knee prosthesis with a long tibial stem extension, and subsequently, their fractures united. Both patients recovered uneventfully.

Telomere lengths in human oocytes, cleavage stage embryos and blastocysts.

Telomeres are repeated sequences that protect the ends of chromosomes and harbour DNA repair proteins. Telomeres shorten during each cell division in the absence of telomerase. When telomere length becomes critically short, cell senescence occurs. Telomere length therefore reflects both cellular ageing and capacity for division. We have measured telomere length in human germinal vesicle (GV) oocytes and preimplantation embryos, by quantitative fluorescence in situ hybridization (Q-FISH), providing baseline data towards our hypothesis that telomere length is a marker of embryo quality. The numbers of fluorescent foci suggest that extensive clustering of telomeres occurs in mature GV stage oocytes, and in preimplantation embryos. When calculating average telomere length by assuming that each signal presents one telomere, the calculated telomere length decreased from the oocyte to the cleavage stages, and increased between the cleavage stages and the blastocyst (11.12 versus 8.43 versus 12.22 kb, respectively, P < 0.001). Other methods of calculation, based upon expected maximum and minimum numbers of telomeres, confirm that telomere length in blastocysts is significantly longer than cleavage stages. Individual blastomeres within an embryo showed substantial variation in calculated average telomere length. This study implies that telomere length changes according to the stage of preimplantation embryo development.

Persistent knee instability following revision total knee arthroplasty.

Instability is an important cause of failure following total knee arthroplasty (TKA). Knee stability needs to be optimal in both the coronal and sagittal planes. We describe failed revision TKA with persistent deformity and instability secondary to a deficient medial collateral ligament in a 71-year-old Chinese woman. Revision knee arthroplasty using constrained implants was performed on her with good result. During both primary and revision TKA, assessment of knee stability is critical. Constrained prosthesis would need to be considered when there is significant ligamentous deficiency.

The relationship between postoperative complications and outcomes after hip fracture surgery.

INTRODUCTION: We studied the prevalence of postoperative complications in a series of consecutive patients who received surgery for hip fractures in a major public hospital in Singapore. We also studied the predictors for the occurrence of complications and the impact of these complications on patient outcomes. MATERIALS AND METHODS: A retrospective chart review of patients admitted with hip fracture, from March to November 2001, was carried out. Patients were classified as having postoperative complications if they developed any of the following conditions after surgery: dislocation of prosthesis, deep vein thrombosis, postoperative confusion, foot drop, stroke, cardiac arrhythmias or acute myocardial infarctions, urinary retention, urinary tract infection, pneumonia, wound infection and incident pressure sores. RESULTS: Of the 180 patients studied, 60 developed postoperative complications. Significant predictors of complications after logistic regression included being of female gender [odds ratio (OR), 2.79; 95% confidence interval (CI), 1.13 to 6.89] and pre-fracture mobility status (OR for independent ambulators 0.45; 95% CI, 0.23 to 0.87), but not the age of the patients. Postoperative complications significantly affected the length of stay within the acute hospital (beta coefficient, 6.42; 95% CI, 2.55 to 10.29), but were not associated with a decline in mobility status at 3 months post-fracture, eventual discharge destination or readmission within 1 year. CONCLUSION: Postoperative complications are common after surgery for hip fractures and result in significantly longer hospitalisation periods. Significant predictors for such complications include being of female gender and pre-fracture mobility. Age, in itself, does not result in a higher risk of complications and should not preclude older hip fracture patients from surgical management.

Hip fractures in nonagenarians--a study on operative and non-operative management.

Hip fractures in nonagenarians represent a special group because of their advanced age and co-morbidities. Surgery is advocated for their younger counterparts but may not appear desirable in nonagenarians. Eighty-four patients were studied over a 2-year period. There were 73 female and 11 male patients. Forty-seven patients sustained an intertrochanteric fracture of the femur. 37 suffered a neck of femur fracture. ASA score of II was the largest group with 51. At least 62 had one co-morbidity or more; 46 were considered demented with a mental test score of less than 7. The mean length of stay was 31 days. Treatment consisted of either traction or surgery. Forty-six patients were managed surgically and 38 non-surgically. Patient review was done 2 years after the fracture. The overall rate of complications was 52% for the operative and non-operative groups. Death outcome at 24 months was not significantly affected by ASA status, number of co-morbidities at admission, or between surgical and non-surgical treatment. However, there was statistical significance between death and the mini-mental test score of less than 7 (P < 0.05). Forty-three patients were still alive after 2 years; of which 27 had been treated surgically and 16 non-surgically. The overall mortality in both operative and non-operative groups is 49%. Surgery significantly increases the ability for independent ambulation (P < 0.01). Therefore the outcome of non-operative and non-operative treatment in nonagenarians with hip fractures is poor due to the high rates of mortality and morbidity.

Telomere length measurement in mouse chromosomes by a modified Q-FISH method.

Telomeres are physical ends of mammalian chromosomes that dynamically change during the lifetime of a cell or organism. In order to understand mechanisms responsible for telomere dynamics, it is necessary to develop methods for accurate telomere length measurement. The most sensitive method for measuring telomere length in mouse chromosomes is quantitative fluorescence in situ hybridization (Q-FISH). The usual protocol for Q-FISH requires plasmids with variable numbers of telomeric repeats and fluorescence beads as calibration standards. Here, we describe a Q-FISH protocol in which two mouse lymphoma cell lines with well-defined telomere lengths are used as calibration standards. Using this protocol we demonstrate that reproducible results can be obtained in a set of four different mouse cell lines. This method can be adapted so that any pair of mammalian cell lines can serve as an internal calibration standard.

Lack of spontaneous and radiation-induced chromosome breakage at interstitial telomeric sites in murine scid cells.

Interstitial telomeric sites (ITSs) in chromosomes from DNA repair-proficient mammalian cells are sensitive to both spontaneous and radiation-induced chromosome breakage. Exact mechanisms of this chromosome breakage sensitivity are not known. To investigate factors that predispose ITSs to chromosome breakage we used murine scid cells. These cells lack functional DNA-PKcs, an enzyme involved in the repair of DNA double-strand breaks. Interestingly, our results revealed lack of both spontaneous and radiation-induced chromosome breakage at ITSs found in scid chromosomes. Therefore, it is possible that increased sensitivity of ITSs to chromosome breakage is associated with the functional DNA double-strand break repair machinery. To investigate if this is the case we used scid cells in which DNA-PKcs deficiency was corrected. Our results revealed complete disappearance of ITSs in scid cells with functional DNA-PKcs, presumably through chromosome breakage at ITSs, but their unchanged frequency in positive and negative control cells. Therefore, our results indicate that the functional DNA double-strand break machinery is required for elevated sensitivity of ITSs to chromosome breakage. Interestingly, we observed significant differences in mitotic chromosome condensation between scid cells and their counterparts with restored DNA-PKcs activity suggesting that lack of functional DNA-PKcs may cause a defect in chromatin organization. Increased condensation of mitotic chromosomes in the scid background was also confirmed in vivo. Therefore, our results indicate a previously unanticipated role of DNA-PKcs in chromatin organisation, which could contribute to the lack of ITS sensitivity to chromosome breakage in murine scid cells.

A case of anterior interosseous nerve syndrome after peripherally inserted central catheter (PICC) line insertion.

Palsies involving the anterior interosseous nerve comprise less than 1% of all upper extremity nerve palsies. Patients often present initially with acute pain in the proximal forearm, lasting several hours to days. The pain subsides, to be followed by paresis or total paralysis of the pronator quadratus, flexor pollicis longus and the radial half of the flexor profundus, either individually or together. Patients with a complete lesion will have a characteristic pinch deformity. We report a case of anterior interosseous syndrome in a 42-year-old male. The patient was admitted initially for chronic osteomyelitis of the left calcaneum. He had a peripherally inserted central catheter (PICC) line inserted into a brachial vein for the administration of intravenous antibiotics, and developed anterior interosseous nerve palsy as a complication of this procedure. The catheter was subsequently removed and a new line was placed on the other side, and his neurological deficit has been improving since. This case highlights the potential hazards of venupuncture or arterial puncture of the brachial vein or artery respectively, even under controlled conditions with the benefit of ultrasound guidance. It also serves as a reminder to look out for the complications of these common procedures, and to be able to react appropriately when they arise.

History of the Singapore Orthopaedic Association.

Since emerging from the shadows of General Surgery, the specialty of Orthopaedic Surgery in Singapore has grown from strength to strength. The year 2002 commemorates 50 years of orthopaedic specialty practice in Singapore. It also celebrates the 34th birthday of the Singapore Orthopaedic Association and coincides with the 25th Annual Scientific Meeting. The Singapore Orthopaedic Association, from its humble beginnings, has grown into a credible organisation that aims to fulfill the academic aspirations of its members as well as serve as a bridge to other related organisations abroad. Apart from its academic activities, it also aims to broaden the bond of friendship with other orthopaedic organisations.

Long but dysfunctional telomeres correlate with chromosomal radiosensitivity in a mouse AML cell line.

PURPOSE: To compare the chromosomal radiosensitivity of C3H mouse acute myeloid leukaemia (AML) cell lines 7926 and 8709 and to investigate the mechanistic basis of the radiosensitivity observed in 7926. MATERIALS AND METHODS: Yields of chromosome aberrations following X-irradiation were determined in Giemsa-stained metaphases. Cell cycle phase distributions were determined by BrdU incorporation and microscopy, apoptosis was assessed by caspase assays. Telomerase activity (TRAP assay), telomere length (Q-FISH and Southern blotting) and telomere function (Robertsonian-like fusion formation) were also examined. The expression levels of telomerase components, telomerase regulators and DNA PKcs were determined on Northern blots. RESULTS: A total of 4.5-7.6-fold elevated chromosome aberration yields were found in 7926 by comparison with 8709 3-24h after 0.5 and 1 Gy X-ray exposure. This difference could not be accounted for by differences in chromatid break-rejoining rates, cell cycle phase distribution or the induction of apoptosis. Telomeres and telomerase were dysfunctional in 7926. However, average telomere length was approximately two-fold greater than in 8709. CONCLUSION: Defective telomere function in 7926 correlates with chromosomal radiosensitivity. This implicates telomere function in addition to telomere length as a determinant of chromosomal radiosensitivity.

Predictors of outcome of floating knee injuries in adults: 89 patients followed for 2-12 years.

Of the 98 floating knee injuries that were consecutively treated from 1987 to 1997, 89 patients were available for analysis. There were 80 males and 9 females, ranging from 15 to 70 years old. Average follow-up was 5 (2-12) years. Injury severity scores ranged from 18 to 45. 21 fractures were intra-articular. 55 fractures were open. Substantial comminuted and segmental fractures occurred in 57 cases and 35 cases, respectively. Multivariate analysis showed that increasing age was associated with delays in bony union and full weight bearing ability. An increase in the number of pack years smoked at the time of injury predicted the likelihood of knee stiffness, delays in bony union and full weight bearing ability. Higher injury severity scores were associated with delayed full weight bearing ability. The presence of open fractures predicted the likelihood of knee stiffness and delayed full weight bearing ability. Comminuted fractures were associated with malunion, and segmental fractures with delayed bony union. Using the outcome of floating knee injuries as fair or poor, according to Karlström and Olerud's criteria, we constructed a preoperative prognostic scoring scale which showed a sensitivity of 0.72 and a specificity of 0.90.

The pattern of ambulance arrivals in the emergency department of an acute care hospital in Singapore.

OBJECTIVES: (1) To determine the pattern of ambulance arrivals in the emergency department (ED) and (2) to review resource allocation based on these data. METHODS: All (13 697) ambulance arrivals in 1996 to the ED of Tan Tock Seng Hospital were studied and where relevant compared with the walk in and total arrivals of the same year. The following data were obtained from computer records: (a) patients' demographic data; (b) number of ambulance arrivals by hour; (c) the classification of the ambulance arrivals by emergency or non-emergency, trauma or non-trauma; (d) cause of injury for trauma cases; (e) discharge status. RESULTS: The ambulance arrivals in 1996 constituted 12.4% of the patient load for this department. There was no difference in modes of patient arrival to the ED by sex and ethnic group. However, there was significant evidence to show that more patients age > 60 came by ambulance than those age < 12 (p << 0.01). Some 98.5% of the ambulance arrivals were emergencies; 40.7% of the ambulance arrivals were attributable to trauma versus 27.3% of the walk in arrivals. The majority of the trauma cases brought in by ambulance were because of road traffic accidents (15.3%) or home accidents (7.4%). The peak in ambulance arrivals was between 2100-2300 hours compared with 1000-1200 for the walk in arrivals. More than half of the ambulance arrivals were admitted. CONCLUSION: In planning resource allocation and in the development of contingency plans, the resource use of ambulance patients and the pattern of their arrivals should be taken into account.

Timing of microcirculatory injury from ischemia reperfusion.

The low flow state that results from ischemia and reperfusion injury is a potentially reversible process that is important in numerous clinical situations. However, the point in time during the course of reperfusion where tissue injury becomes irreversible is unknown. This experiment evaluated the continuum of tissue damage in skeletal muscle after ischemic insult by quantifying the number of flowing capillaries and percentage muscle necrosis in a male Wistar rat skeletal muscle model. A gracilis muscle flap was raised on the vascular pedicle of 39 male Wistar rats and examined at 832x using intravital videomicroscopy. The numbers of flowing capillaries in five consecutive high-power fields were counted for baseline values. The flap was then subjected to 4 hours of global ischemia (except in sham animals, n = 7) by placing a microvascular clamp on the pedicle artery and vein. Upon reperfusion, flowing capillaries were counted in the same five high-power fields at intervals of 5, 15, 30, and 60 minutes, then at 2 to 8 (1-hour intervals), 24, and 48 hours. The gracilis muscle was then harvested at these intervals during reperfusion and assessed for viability. Compared with baseline, flowing capillaries from the ischemia and reperfusion group (mean +/- SEM) decreased significantly in the first 8 hours of reperfusion (7.7 +/- 0.2 to 3.2 +/- 0.3, p < 0.001) with minimal change noted from 8 to 48 hours. Percentage muscle necrosis increased progressively in ischemia and reperfusion preparations from 1 to 7 hours of reperfusion (16.5 +/- 2.6 percent to 38.9 +/- 1.2 percent, p < 0.001). No significant change in muscle necrosis in the ischemia and reperfusion group was noted between 7 and 48 hours. Sham preparations showed no change in the number of flowing capillaries through 3 hours of reperfusion, with a slight decrease at 24 hours. This rat gracilis microcirculation skeletal muscle model demonstrates a heterogeneous reperfusion injury. The decrease in flowing capillaries correlated with the increase in percentage necrosis and appeared to stabilize at the 7- to 8-hour interval. This finding may have important implications for the timing of interventions aimed at minimizing tissue damage from ischemia-reperfusion.

Emergency department organisation for disasters: a review of emergency department disaster plans in public hospitals of Singapore.

Disaster management plans of emergency departments (EDs) in four major public hospitals were reviewed. A comparison was made between these plans, and they were analyzed to gain an understanding of the differing objectives and doctrines behind the practices. These were summarized into five major management concepts, which are considered to be critical to the success of a disaster plan: 1) staff mobilization systems (cascading vs batch mobilization); 2) staff deployment systems; 3) team organization (surgeons vs residents); 4) area management (the role of the area manager); 5) casualty volume management (accommodation vs expansion vs extension concepts). The concepts derived should serve as a useful guide to the development of an ED disaster plan and potentially influence how new ED facilities could be planned.

Surgical results of intercondylar fractures of the adult femur.

INTRODUCTION: Although surgical treatment of intercondylar fractures of the adult femur gives satisfactory results in the majority of cases, there are complications reported with operative management. We aim to analyse the surgical results of these cases performed in our institution and compare them to other reported series. MATERIALS AND METHODS: A total of 16 patients with intercondylar fractures of the femur were operatively treated from 1989 to 1997. The ages of these patients ranged from 24 to 77 years, with a mean age of 42 years. Average length of follow-up was 28 months. The fractures were classified according to AO classification. Twenty-five per cent of the fractures were significantly comminuted. They were internally fixed with various implants such as cancellous screw fixation, dynamic condylar screw plate, condylar blade plate and condylar buttress plate. RESULTS: Average time to full weight bearing was 12 weeks. Results of treatment were assessed according to the criteria described by Shelbourne. Eighty-three per cent of minimally comminuted fractures had a good result, but only 50% of significantly comminuted fractures did well. CONCLUSIONS: We recommend the use of anterior midline approach and condylar buttress plate for very comminuted fractures. Infection, if detected early and treated aggressively could avoid a poor outcome. Elderly patients should benefit from internal fixation and earlier mobilisation.

The Ottawa Ankle Rules in Asia: validating a clinical decision rule for requesting X-rays in twisting ankle and foot injuries.

This was a study to determine if the Ottawa Ankle Rules (OAR) for requesting x-ray studies in twisting ankle and foot injuries are applicable in our Asian population. Four hundred ninety-four consecutive eligible patients presenting to the emergency department with twisting injuries about the ankle were examined by emergency physicians for clinical criteria requiring ankle and foot x-ray studies according to the OAR. Four hundred eighty-eight of these patients underwent x-ray studies that were interpreted by a radiologist. The sensitivity and specificity of the OAR for predicting the presence of fracture were calculated to be 0.9 and 0.34, respectively. When the rules were modified to cast a wider screening net, sensitivity improved to 0.99. We conclude that the OAR are not applicable to our population because of inadequate sensitivity, but when modified become acceptable and can reduce the number of x-ray studies requested by 28%.

L-selectin and leukocyte function in skeletal muscle reperfusion injury.

HYPOTHESIS: Treatment with anti-L-selectin monoclonal antibody will reduce venular neutrophil-endothelial rolling (flux and velocity) and adhesion associated with ischemia reperfusion injury in rat skeletal muscle. DESIGN: Prospective, randomized experimental trials. SETTING: Basic science research laboratory. MATERIALS: Male Wistar rats weighing 109 +/- 5 g (mean +/- SEM). INTERVENTIONS: Gracilis pedicle muscle flaps were elevated and microcirculation was observed by intravital microscopy. Two groups were evaluated: (1) the control group, which received 4 hours of global ischemia, and (2) the experimental group, which received 4 hours of global ischemia, plus treatment with anti-L-selectin monoclonal antibody 30 minutes before reperfusion. MAIN OUTCOME MEASURES: The number of rolling and adherent leukocytes in postcapillary venules were counted in the 2 groups at baseline and at 1 through 5, 10, 15, 20, 30, 45, and 60 minutes of reperfusion. RESULTS: Treatment with the monoclonal antibody to L-selectin significantly reduced the number of rolling leukocytes (flux) at 2 through 5, 20, 30, 45, and 60 minutes of reperfusion compared with controls (P<.05). Use of the monoclonal antibody significantly reduced the number of adherent neutrophils at 5, 10, 15, 20, 30, 45, and 60 minutes of reperfusion (P<.05). There was no significant difference in leukocyte velocity. CONCLUSION: L-Selectin plays a significant role in leukocyte rolling and adherence to venular endothelium in rat skeletal muscle ischemia reperfusion injury.

Extent and appropriateness of emergency department services usage by foreign workers in Singapore.

The objective of this study was to determine the extent and appropriateness of emergency department services usage by foreign workers. A prospective questionnaire survey of foreign workers who attended the Emergency Department (ED) of Tan Tock Seng Hospital was conducted from 30 December 1996 to 29 January 1997. A foreign worker was defined as a non-citizen, non-permanent resident working in Singapore, excluding students and tourists. Demographic and clinical data were collected. During the study period, 7409 patients above the age of 15 attended the ED of which 1174 (15.8%) were foreign workers. Forty-seven per cent of these foreign workers could not speak English, of whom 48.2% did not come with any English-speaking companion. Most of their ED visits were on weekdays and during office hours. Of the foreign workers, 43.1% were classified as non-emergency by ED doctors compared to 6.7% of other ED patients (P < 0.01). Trauma-related complaints accounted for 43.4% while febrile and minor infectious illnesses accounted for 26.7% of foreign workers' complaints. Admissions from ED into the hospital were 17.1% for foreign workers and 28.3% (P < 0.01) for other patients. Language barrier and lack of information on types of health care services available could have led to the high proportion of inappropriate use of ED services by foreign workers. Most of their complaints were minor injuries and illnesses which could be managed by non-ED health care providers. Care provided across a language barrier raises ethical and medico-legal questions. A multi-agency approach involving the Manpower and Health Ministries, employer and foreign worker representatives is needed to eliminate language barrier and help these workers to use health care services appropriately.

Transscaphoid perilunate fracture/dislocations--results of surgical treatment.

Sixteen cases of dorsal transscaphoid perilunate fracture/dislocations in 15 patients were treated by open reduction and internal fixation of the scaphoid with a Herbert screw and/or Kirschner wires. All patients were male, with a mean age of 31 years. The average follow-up period was 3 years. These perilunate dislocations were transscaphoid in 13 cases, and transstyloid and transscaphoid in 3 cases. There was one case of median nerve deficit preoperatively. Open reduction was performed through a volar approach in all cases. Herbert screw fixation of the scaphoid was performed on 13 cases, of which supplemental Kirschner wires were used in 2 cases. Three cases had fixation with Kirschner wires only. There were 2 cases of non-union which required bone grafting on follow-up. A clinical evaluation scoring system assessing pain, occupational ability, range of motion and grip strength was used. Based on this, there were 10 excellent to good (62.5%) and 6 fair results. For the majority of our patients, surgical outcome is characterised by acceptable relief of pain, functional motion and grip strength.