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Biomedical subjects

J Lim

Publications and source records attributed to J Lim.

At least 19 recordsLinked to original sources

Laparoscopic feeding jejunostomy in esophagogastric cancer.

BACKGROUND: Patients with esophagogastric malignancies often require nutritional supplementation in the perioperative period, especially in the setting where neoadjuvant therapy may delay tumor resection. A simple technique is described here that can be performed at the time of staging laparoscopy and that has not been described before. RESULTS: Forty-three patients treated over a 4-year period who had a laparoscopic feeding jejunostomy placed at the time of staging laparoscopy were reviewed. Of these, 35 had preoperative chemotherapy according to a modified MRC OEO2 protocol. In the period between staging and eventual resection, 32% required immediate feeding, and in 14% of those who were thought not to need feeding it later became necessary. More patients gained weight or had a rise in albumin in the group that had jejunal feeding (p < 0.05). The mean time to surgery was 10 weeks. There were no conversions to an open procedure, nor were there any laparotomies for tube-related complications. Dislodgement was recorded in 6 patients; blockage, in 4. In most of these cases a simple bedside replacement of the tube was all that was required. Mean time in the operating room for each procedure was 44 minutes. CONCLUSIONS: Laparoscopic percutaneous feeding jejunostomy is a safe and simple technique that adds little to the morbidity and cost of managing patients with esophagogastric cancers. It facilitates optimization of nutrition in the perioperative period for these patients, especially in those receiving preoperative chemotherapy.

Adult↗

Minimally invasive Oxford medial unicompartmental knee arthroplasty. A note of caution!

We present the peak outcome results of the Oxford medial unicompartmental arthroplasty through a minimally invasive surgical incision. This prospective study included 78 Oxford medial unicompartmental knee replacements in 68 patients. At the 2 year review the patients achieved a mean Oxford Knee Score of 38.3. This was not significantly different to the 2 year results of the phase 2 Oxford knee carried out using a standard parapatellar approach when patients achieved a mean OKS of 36.0. Four unicompartmental knee replacements required revision for unexplained pain, deep infection, aseptic loosening and bearing dislocation. Minimally invasive joint replacement is attractive to both patients and surgeons, but is technically demanding with complications inherent to limited access.

Adult↗

The mitogen-activated/extracellular signal-regulated kinase kinase 1/2 inhibitor U0126 induces glial fibrillary acidic protein expression and reduces the proliferation and migration of C6 glioma cells.

The extracellular signal-regulated kinase (ERK) signaling pathway has been implicated in diverse cellular functions. ERK and its activating kinase, mitogen-activated/extracellular signal-regulated kinase kinase (MEK), are downstream of cell surface receptors known to be up-regulated in many malignant gliomas. We sought to investigate the role of ERK in glioma cell migration, proliferation and differentiation using the rat-derived C6 glioma cell line and the MEK inhibitor, U0126. Treatment of C6 cells with U0126 caused a significant concentration-dependent reduction in cell proliferation and migration and also induced expression of glial fibrillary acidic protein, a marker of astrocytic differentiation. These results suggest that the ERK pathway regulates glioma cell proliferation, migration and differentiation.

Analysis of Variance↗

N-3 fatty acids inhibit vascular calcification via the p38-mitogen-activated protein kinase and peroxisome proliferator-activated receptor-gamma pathways.

Fish oil supplementation is associated with lower risk of coronary artery disease in humans, and it has been shown to reduce ectopic calcification in an animal model. However, whether N-3 fatty acids, active ingredients of fish oil, have direct effects on calcification of vascular cells is not clear. In this report, we investigated the effects of eicosapentaenoic acid and docosahexaenoic acid (DHA) on osteoblastic differentiation and mineralization of calcifying vascular cells (CVCs), a subpopulation of bovine aortic medial cells that undergo osteoblastic differentiation and form calcified matrix in vitro. Results showed that N-3 fatty acids inhibited alkaline phosphatase (ALP) activity and mineralization of vascular cells, suggesting that they directly affect osteoblastic differentiation in vascular cells. By Western blot analysis, DHA activated p38-mitogen-activated protein kinase (MAPK) but not extracellular-regulated kinase (ERK) or Akt. An inhibitor of p38-MAPK partially reversed the inhibitory effects of DHA on osteoblastic differentiation and mineralization. Transient transfection experiments showed that DHA also activated peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Both p38-MAPK activator and PPAR-gamma agonists reproduced the inhibitory effects of DHA on CVC mineralization. Pretreatment with DHA also inhibited interleukin-6-induced ALP activity and mineralization. Together, these results suggest that N-3 fatty acids directly inhibit vascular calcification, and that the inhibitory effects are mediated by the p38-MAPK and PPAR-gamma pathways.

Animals↗

Oral appliances for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea-hypopnoea (OSAH) is a syndrome characterised by recurrent episodes of partial or complete upper airway obstruction during sleep that are usually terminated by an arousal. Nasal continuous positive airway pressure (CPAP) is the primary treatment for OSAH , but many patients are unable or unwilling to comply with this treatment. Oral appliances (OA) are an alternative treatment for OSAH. OBJECTIVES: The objective was to review the effects of OA in the treatment of OSAH in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register. Searches were current as of June 2005. Reference lists of articles were also searched. SELECTION CRITERIA: Randomised trials comparing OA with control or other treatments in adults with OSAH . DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Study authors were contacted for missing information. MAIN RESULTS: Sixteen studies (745 participants) met the inclusion criteria. All the studies had some shortcomings, such as small sample size, under-reporting of methods and data, and lack of blinding. OA versus control appliances (six studies): OA reduced daytime sleepiness in two crossover trials (WMD -1.81;95%CI -2.72 to -0.90), and improved apnoea-hypopnoea index (AHI) (-10.78; 95% CI-15.53 to -6.03 parallel group data - five studies). OA versus CPAP (nine studies): OA were less effective than CPAP in reducing apnoea-hypopnoea index (parallel group studies: WMD 13 (95% CI 7.63 to 18.36), two trials; crossover studies: WMD 7.97; (95% CI 6.38 to 9.56, seven trials). However, no significant difference was observed on symptom scores. CPAP was more effective at improving minimum arterial oxygen saturation during sleep compared with OA. In two small crossover studies, participants preferred OA therapy to CPAP. OA versus corrective upper airway surgery (one study): Symptoms of daytime sleepiness were initially lower with surgery, but this difference disappeared at 12 months. AHI did not differ significantly initially, but did so after 12 months in favour of OA. AUTHORS' CONCLUSIONS: There is increasing evidence suggesting that OA improves subjective sleepiness and sleep disordered breathing compared with a control. CPAP appears to be more effective in improving sleep disordered breathing than OA. The difference in symptomatic response between these two treatments is not significant, although it is not possible to exclude an effect in favour of either therapy. Until there is more definitive evidence on the effectiveness of OA in relation to CPAP, with regard to symptoms and long-term complications, it would appear to be appropriate to recommend OA therapy to patients with mild symptomatic OSAH, and those patients who are unwilling or unable to tolerate CPAP therapy. Future research should recruit patients with more severe symptoms of sleepiness, to establish whether the response to therapy differs between subgroups in terms of quality of life, symptoms and persistence with usage. Long-term data on cardiovascular health are required.

Adult↗

Genomic amplification of MET with boundaries within fragile site FRA7G and upregulation of MET pathways in esophageal adenocarcinoma.

Esophageal adenocarcinoma (EA) is characterized by a poor prognosis making the identification of clinically targetable proteins essential for improving patient outcome. We report the involvement of multiple alterations of the MET pathway in EA development and progression. Microarray analysis of Barrett's metaplasia, dysplasia, and EA revealed overexpression of the MET oncogene in EAs but only those with MET gene amplification. STS-amplification mapping revealed that the boundary of the MET amplicon in these EAs is defined by fragile site FRA7G. We also identified an amplicon at 11p13 that resulted in amplification and overexpression of CD44, a gene involved in MET autophosphorylation upon HGF stimulation. Tissue microarrays with phospho-MET-specific antibodies demonstrated a uniformly high abundance of MET activation in primary EA and cells metastatic to lymph nodes but to a lesser extent in a subset of metaplastic and dysplastic Barrett's samples. Increased expression of multiple genes in the MET pathway associated with invasive growth, for example, many MMPs and osteopontin, also was found in EAs. Treatment of EA-derived cell lines with geldanamycin, an inhibitor for tyrosine kinases including MET receptor kinase, reduced cell migration and induced EA cell apoptosis. The data indicate that upregulation of the MET pathway may contribute to the poor outcome of EA patients and that therapeutic agents targeting this pathway may help improve patient survival.

Adenocarcinoma↗

Intrathecal implants of microencapsulated xenogenic chromaffin cells provide a long-term source of analgesic substances.

Adrenal medullary chromaffin cells secrete several neuroactive substances including catecholamines and opioid peptides that produce analgesic effects in the central nervous system. This study was designed to investigate whether intrathecal microencapsulated chromaffin cells could release analgesic materials producing antiallodynic effects on the chronic neuropathic pain in rats induced by chronic constriction injury (CCI) of the sciatic nerve. Prior to intrathecal implantation, chromaffin cells were encapsulated with alginate and poly-L-lysine to protect them from the host immune system. Behavior tests were performed before CCI, 1 week later, and at 4, 7, 14, 21, 28 days postimplantation. At the end of study, we performed cerebrospinal fluid (CSF) collection and implant retrieval. We observed that intrathecal implantation of encapsulated xenogenic chromaffin cells reduced the mechanical and cold allodynia in a model of neuropathic pain. CSF levels of catecholamines and metenkephalin in the rats that received implants were higher than the controls. In addition, we observed chronic survival of implants. These results suggested that intrathecal microencapsulated chromaffin cells may represent a new approach to chronic neuropathic pain management.

Absorbable Implants↗

Characterization of cerebrovascular reactivity after craniectomy for acute brain injury.

Analysis of slow waves in arterial blood pressure (ABP) and intracranial pressure (ICP) has been used as an index to describe cerebrovascular pressure-reactivity. It has been previously demonstrated that the pressure-reactivity index (PRx) can be used to reflect global cerebrovascular reactivity with changes in ABP. A positive PRx signifies a positive association between ABP and ICP, indicating a non-reactive vascular bed, while a negative PRx is reflective of intact cerebral autoregulation, where ABP waves provoke inversely correlated waves in ICP. To date, there has been no characterization of pressure-reactivity following decompressive craniectomy. In this prospective observational study, 33 patients who underwent surgery for acute brain injury with mass lesions for which the bone flap was left out were studied. The PRx was calculated as a moving correlation coefficient between 30 consecutive samples of values of ICP and ABP averaged for a period of 10 s. The time profiles of mean PRx values at 6-hourly intervals were analysed and compared with that in seven patients treated by medical therapy alone. The initial mean PRx 6 h after surgery was positive, indicative of disturbed pressure-reactivity. With time, PRx trended towards a more negative value, suggestive of an improving cerebrovascular autoregulatory reserve. The mean PRx 24 h after surgery was 0.28 (+/-0.26), while the mean PRx 72 h after surgery was 0.15 (+/-0.25) (p = 0.012). In contrast, the mean PRx in patients that were not decompressed did not change significantly with time (p = 0.357). Surgery in acute brain injury for which the bone flap is left out in anticipation of raised intracranial pressure in the postoperative period leads to an improved PRx as compared with controls. Craniectomy in this situation may have a contribution to the restoration of disturbed cerebrovascular pressure-reactivity.

Adult↗

Correlating motor performance with surgical error in laparoscopic cholecystectomy.

BACKGROUND: Analysis of motor performance in minimally invasive surgery (MIS) is a new field with applications in surgical training, surgical simulators, and robotics. Force/torque and derivatives of tool tip position (velocity, acceleration, and jerk) are examples of measures of motor performance (MMPs). Few studies have measured MMPs or have correlated MMPs with surgical performance during MIS on humans. The objectives of this study were to determine the feasibility of a novel multimodal system to quantify MMPs in laparoscopic cholecystectomy and to attempt to correlate MMPs with the magnitude of error as a measure of surgical performance. METHODS: Novice and expert surgeons performed laparoscopic cholecystectomies in two groups of three patients each. MMPs were obtained using a combination of optical and electromagnetic tool tip tracking and a force/torque sensor on a modified Maryland dissector. Error scores for laparoscopic cholecystectomy were calculated using a previously validated system. Novice and expert measurements were compared, and correlations were made between error scores and MMPs. RESULTS: Error scores were similar between novices and experts. Novice surgeons had a significantly greater mean velocity (566 +/- 83 vs 85 +/- 32 mm/s, p = 0.006) and acceleration (2,600 +/- 760 vs 440 +/- 174 mm/s2, p = 0.050) compared to expert surgeons. Force (16.5 +/- 4.6 vs 18.3 +/- 6.0 N, p = 0.829), position (121 +/- 25 vs 135 +/- 72 mm, p = 0.863), and jerk (19,600 +/- 7,410 vs 2,430 +/- 367 mm/s3, p = 0.138) were similar between groups. A positive correlation was found in novice surgeons between error score and jerk (Pearson correlation, 0.999; p = 0.035). CONCLUSIONS: It is feasible to quantify MMPs in laparoscopic cholecystectomy. Novice and expert surgeons can be differentiated by MMPs; moreover, there may be a positive correlation between jerk and error score in novice surgeons.

Adult↗

Surgery for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea/hypopnoea syndrome(OSAHS) is the periodic reduction or cessation of airflow during sleep. The syndrome is associated with loud snoring, disrupted sleep and observed apnoeas. Surgery for obstructive sleep apnoea/hypopnoea syndrome aims to alleviate symptoms of daytime sleepiness, improve quality of life, and reduce the signs of sleep apnoea recorded by polysomnography. OBJECTIVES: The objective of this review was to assess the effects of any type of surgery for the treatment of the symptoms of obstructive sleep apnoea/hypopnoea syndrome in adults. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register and reference lists of articles. We contacted experts in the field, research dissemination bodies and other Cochrane Review Groups. Searches were current as of July 2005. SELECTION CRITERIA: Randomised trials comparing any surgical intervention for obstructive sleep apnoea/hypopnoea syndrome with other surgical or non-surgical interventions or no intervention. DATA COLLECTION AND ANALYSIS: Two reviewers assessed electronic literature search results for possibly relevant studies. Characteristics and data from studies meeting the inclusion criteria were extracted and entered into RevMan 4.2. MAIN RESULTS: In the 2005 update for this review eight studies (412 participants) of mixed quality met the inclusion criteria. Data from seven studies were eligible for assessment in the review. No data could be pooled. Uvulopalatopharyngoplasty (UPPP) versus conservative management (one trial): An un validated symptom score showed intermittent significant differences over a 12-month follow-up period. No differences in Polysomnography (PSG) outcomes were reported. Laser-assisted uvulopalatoplasty (LAUP) versus conservative management/placebo (two trials): One study recruited mixed a population, and separate data could not be obtained for this trial. In the other study no significant differences in Epworth scores or quality of life reported. A significant difference in favour of LAUP was reported in terms of apnoea hypopnoea index (AHI) and frequency and intensity of snoring. UPPP versus oral appliance (OA) (one trial): AHI was significantly lower with OA therapy than with UPPP. No significant differences were observed in quality of life. UPPP versus lateral pharyngoplasty (lateral PP) (one trial): No significant difference in Epworth scores, but a greater reduction in AHI with lateral PP was reported. Tongue advancement (mandibular osteotomy) + PPP versus tongue suspension + PPP (one trial): There was a significant reduction in symptoms in both groups, but no significant difference between the two surgery types. Complications reported with all surgical techniques included nasal regurgitation, pain and bleeding. These did not persist in the long term. An additional study assessed the effects of four different techniques. No data were available on between group comparisons. Multilevel temperature-controlled radiofrequency tissue ablation (TCRFTA) versus sham placebo and CPAP (one trial): There was an improvement in primary and secondary outcomes of TCRFTA over sham placebo and but no difference in symptomatic improvement when compared with CPAP. AUTHORS' CONCLUSIONS: There are now a small number of trials assessing different surgical techniques with inactive and active control treatments. The studies assembled in the review do not provide evidence to support the use of surgery in sleep apnoea/hypopnoea syndrome, as overall significant benefit has not been demonstrated. The participants recruited to the studies had mixed levels of AHI, but tended to suffer from moderate daytime sleepiness where this was measured. Short-term outcomes are unlikely to consistently identify suitable candidates for surgery. Long-term follow-up of patients who undergo surgical correction of upper airway obstruction is required. This would help to determine whether surgery is a curative intervention, or whether there is a tendency for the signs and symptoms of sleep apnoea to re-assert themselves, prompting patients to seek further treatment for sleep apnoea.

Adult↗

Linear correlation between stable intracranial pressure decrease and regional cerebral oxygenation improvement following mannitol administration in severe acute head injury patients.

OBJECTIVES: We investigated the relationship between stable decrease in intracranial pressure (ICP) following mannitol administration and variations in regional oxygenation (PtiO2) in severe traumatic brain injured (STBI) patients. METHODS: Fourteen STBI patients (Glasgow Coma Scale score < or = 8) admitted to the neurointensive care unit during a 12-month period were studied. Multiparameter data, including parenchymal tissue oxygen (PtiO2) and carbon dioxide tension, cerebral perfusion pressure, mean arterial pressure; temperature, pH and pressure reactivity index were measured. Point values from 53 mannitol administrations were extracted every five seconds and divided into five consecutive 30-minute epochs. Mean values and trends were identified. Postadministration epoch with maximum decrease in ICP was selected along with the means of the corresponding variables. These data were compared with baseline to derive the delta values. Mean deltaICP was then compared with deltaPtiO2 in each patient using linear correlation. FINDINGS: In patients with ICP0 > 20 mmHg (group A), PtiO2 increased in 69.6% of samples, whereas in group B (ICP0 < 20 mmHg), PtiO2 increased in only 50% of the samples. There was a significant negative correlation between mean deltaICP and deltaPtiO2 in both groups; Group A: r = -0.79 (P = 0.01); Group B: r = -0.92 (P = 0.01). CONCLUSIONS: There is a strong negative correlation between stable decrease in ICP following mannitol administration and improvement in regional oxygenation around the peri-contusional area. The data suggest a potentially favourable interaction between mannitol therapy and cerebral internal milieu in STBI patients.

Acute Disease↗

Changes in cerebral hemodynamics and cerebral oxygenation during surgical evacuation for hypertensive intracerebral putaminal hemorrhage.

OBJECTIVES: The aim of this study was to evaluate the changes in cerebral hemodynamics, tissue oxygenation and blood flow before and after surgery for spontaneous intracerebral hematomas. METHODS: Eleven patients who underwent surgical decompression of spontaneous putaminal hematoma were studied. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygen (PtiO2), and carbon dioxide tensions (PtiCO2), brain pH and regional cerebral blood flow (rCBF) were recorded prior to removing the bone flap and then on skin closure on completion of the operation. RESULTS: Following surgical decompression, mean ICP decreased significantly (P < 0.05); mean CPP, PtiO2, brain pH and rCBF improved although the changes were not significant. CONCLUSION: Surgical decompression for spontaneous intracerebral hematomas leads to significant reductions in ICP. This is accompanied by improvements in CPP, PtiO2 and rCBF in the penumbra.

Aged↗