Biomedical subjects
Publications and source records attributed to T Ho.
Intramedullary schwannomas are rare spinal cord tumours. Correct preoperative diagnosis is essential for proper surgical planning and complete resection. We present a case of cervical intramedullary schwannoma followed by discussion on its preoperative magnetic resonance imaging features and review of the literature.
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AIM: To compare the inter-method agreement in intraocular pressure (IOP) measurements made with four different tonometric methods. METHODS: IOP was measured with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT) in a randomised order in one eye of each of 105 patients with ocular hypertension or glaucoma. Three measurements were made with each method, and by each of two independent GAT observers. GAT interobserver and tonometer inter-method agreement was assessed by the Bland-Altman method. The outcome measures were 95% limits of agreement for IOP measurements between GAT observers and between tonometric methods, and 95% confidence intervals for intra-session repeated measurements. RESULTS: The mean differences (bias) in IOP measurements were 0.4 mm Hg between GAT observers, and 0.6 mm Hg, 0.1 mm Hg, and 0.7 mm Hg between GAT and Tono-Pen, OBF, and NCT, respectively. The 95% limits of agreement were smallest (bias +/-2.6 mm Hg) between GAT observers, and larger for agreement between the GAT and the Tono-Pen, OBF, and NCT (bias +/-6.7, +/-5.5, and +/-4.8 mm Hg, respectively). The OBF and NCT significantly underestimated GAT measurements at lower IOP and overestimated these at higher IOP. The repeatability coefficients for intra-session repeated measurement for each method were +/-2.2 mm Hg and +/-2.5 mm Hg for the GAT, +/-4.3 mm Hg for the Tono-Pen, +/-3.7 mm Hg for the OBF, and +/-3.2 mm Hg for the NCT. CONCLUSIONS: There was good interobserver agreement with the GAT and moderate agreement between the NCT and GAT. The differences between the GAT and OBF and between the GAT and Tono-Pen probably preclude the OBF and Tono-Pen from routine clinical use as objective methods to measure IOP in normal adult eyes.
AIMS: To evaluate the influence of central corneal thickness (CCT) on intraocular pressure (IOP) measurements made with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT). METHODS: CCT was recorded for either eye (randomly selected) of each of 105 untreated patients with ocular hypertension and glaucoma attending the glaucoma research unit at Moorfields Eye Hospital. For each of the selected eyes, IOP was measured with the GAT (two observers), Tono-Pen, OBF, and NCT in a randomised order. The relation of measured IOP and of inter-tonometer differences with CCT and subject age was explored by linear regression analysis. RESULTS: A significant association between measured IOP and CCT was found with each instrument. The change in measured IOP for a 10 mum increase in CCT was 0.28, 0.31, 0.38, and 0.46 for the GAT, Tono-Pen, OBF, and NCT, respectively (all p< or = 0.05). There was a significant association between the NCT/GAT differences and CCT, with a tendency of NCT to overestimate GAT in eyes with thicker corneas. There was a significant association between GAT/Tono-Pen and OBF/Tono-Pen differences and age, with a tendency of GAT and OBF to overestimate the Tono-Pen in eyes of older subjects. CONCLUSION: IOP measurement by all four methods is affected by CCT. The NCT is affected by CCT significantly more than the GAT. Subject age has a differential effect on the IOP measurements made by the GAT and OBF compared to the Tono-Pen.
Trapping of small mammals was conducted at 5 study sites in Kuala Selangor Nature Park (KSNP) from 20-24 June 2005. A total of 11 animals comprising 2 species of rodents, Maxomys whiteheadi and Rattus exulans were caught from 3 sites, i.e from an area of mixed secondary forest and mangrove swamp; an area of mangrove swamp, and from an area of lalang fringing mangrove swamp. From these animals, the following 7 species of ectoparasites were found: Laelaps echidninus, Laelaps nuttalli, Ascoschoengastia indica, Leptotrombidium deliense, Hoplopleura pectinata, Hoplopleura pacifica and Polyplax spinulosa. One of the ectoparasites found, L. deliense is a known vector of scrub typhus and thus may pose potential health risks to visitors to KSNP.
Stapled hemorrhoidectomy is gaining popularity worldwide. One problem that is often encountered is difficulty with insertion of the circular anal dilator because of very protuberant and fatty buttocks and a narrow interischial tuberosity distance. We describe a modification of this device for easier introduction in such patients.
Gene-directed enzyme prodrug therapy (GDEPT) based on the Escherichia coli enzyme, purine nucleoside phosphorylase (PNP), provides a novel strategy for treating slowly growing tumors like prostate cancer (CaP). PNP converts systemically administered prodrug, fludarabine phosphate, to a toxic metabolite, 2-fluoroadenine, that kills PNP-expressing and nearby cells by inhibiting DNA, RNA and protein synthesis. Reporter gene expression directed by a hybrid prostate-directed promoter and enhancer, PSMEPb, was assayed after plasmid transfection or viral transduction of prostate and non-CaP cell lines. Androgen-sensitive (AS) LNCaP-LN3 and androgen-independent (AI) PC3 human CaP xenografts in nude mice were injected intratumorally with an ovine atadenovirus vector, OAdV623, that carries the PNP gene under PSMEPb, formulated with cationic lipid for enhanced infectivity. Fludarabine phosphate was then given intraperitoneally for 5 days at 75 mg/m2/day. PNP expression was evaluated by enzymic conversion of its substrate using reverse phase HPLC. OAdV623 showed excellent in vitro transcriptional specificity for CaP cells. In vivo, expression of PNP persisted for > 6 days after OAdV623 injection and a single treatment provided 100% increase in tumor doubling time and > 50% inhibition of tumor growth for both LNCaP-LN3 and PC3 lines, with increased tumor necrosis and apoptosis and decreased tumor cell proliferation. OAdV623 significantly suppressed the growth of AS and AI human CaP xenografts in mice.
We surveyed 16 subjects with the clinical diagnosis of Noonan Syndrome (NS1) from 12 families and their relevant family members for mutations in PTPN11/SHP2 using direct DNA sequencing. We found three different mutations among five families. Two unrelated subjects shared the same de novo missense substitution in exon 13 (S502T); an additional two unrelated families had a mutation in exon 3 (Y63C); and one subject had the amino acid substitution Y62D, also in exon 3. None of the three mutations were present in ethnically matched controls. In the mature protein model, the exon 3 mutants and the exon 13 mutant amino acids cluster at the interface between the N' SH2 domain and the phosphatase catalytic domain. Six of eight subjects with PTPN11/SHP2 mutations had pulmonary valve stenosis while no mutations were identified in those subjects (N = 4) with hypertrophic cardiomyopathy. An additional four subjects with possible Noonan syndrome were evaluated, but no mutations in PTPN11/SHP2 were identified. These results confirm that mutations in PTPN11/SHP2 underlie a common form of Noonan syndrome, and that the disease exhibits both allelic and locus heterogeneity. The observation of recurrent mutations supports the hypothesis that a special class of gain-of-function mutations in SHP2 give rise to Noonan syndrome.
The steady-state kinetics of a full-length and truncated form of the type 2 human methionine aminopeptidase (hMetAP2) were analyzed by continuous monitoring of the amide bond cleavage of various peptide substrates and methionyl analogues of 7-amido-4-methylcoumarin (AMC) and p-nitroaniline (pNA), utilizing new fluorescence-based and absorbance-based assay substrates and a novel coupled-enzyme assay method. The most efficient substrates for hMetAP2 appeared to be peptides of three or more amino acids for which the values of k(cat)/K(m) were approximately 5 x 10(5) M(-1) min(-1). It was found that while the nature of the P1' residue of peptide substrates dictates the substrate specificity in the active site of hMetAP2, the P2' residue appears to play a key role in the kinetics of peptidolysis. The catalytic efficiency of dipeptide substrates was found to be at least 250-fold lower than those of the tripeptides. This substantially diminished catalytic efficiency of hMetAP2 observed with the alternative substrates MetAMC and MetpNA is almost entirely due to the reduction in the turnover rate (k(cat)), suggesting that cleavage of the amide bond is at least partially rate-limiting. The 107 N-terminal residues of hMetAP2 were not required for either the peptidolytic activity of the enzyme or its stability. Steady-state kinetic comparison and thermodynamic analyses of an N-terminally truncated form and full-length enzyme yielded essentially identical kinetic behavior and physical properties. Addition of exogenous Co(II) cation was found to significantly activate the full-length hMetAP2, while Zn(II) cation, on the other hand, was unable to activate hMetAP2 under any concentration that was tested.
Prostate-specific membrane antigen (PSMA) is an integral membrane protein that is highly expressed on the surface of prostate epithelial cells. It is also expressed on the vascular endothelium of a number of tumor types. We have used an enhancer trap approach with randomly cleaved overlapping DNA fragments from an approximately 55-kb P1 cosmid insert encompassing the 5' half and upstream sequences of the PSMA gene (FOLH1) to isolate an enhancer that strongly activates the FOLH1 core promoter region. The enhancer (PSME) is located in the third intron about 12 kb downstream from the start site of transcription and is characterized by a 72-bp direct repeat within a 331-bp core region. The PSME activates transcription from its own and heterologous promoters in prostate cell lines; enhancement is greatest in the PSMA-expressing cell line LNCaP (>250-fold). The PSME shows essentially no activity in five nonprostate cell lines. PSME-enhanced expression is repressed in the presence of androgen, mimicking the repression of the endogenous FOLH1 gene. The data demonstrate that both cell-type specificity and androgen regulation are intrinsic properties of the enhancer. These properties make the PSME an excellent candidate for regulation of gene expression in gene therapy approaches to prostate cancer.
BACKGROUND: The purpose of this study is to evaluate our experience with the laparoscopic gastric bypass. The technique, weight loss data, and complications are described. METHODS: 1,500 consecutive patients were evaluated prospectively. All patients met NIH criteria for bariatric surgery. Although there have been modifications with respect to staplers, suture material, and dissection techniques, the basic anatomical construct has remained the same, including performing a completely hand-sewn gastrojejunostomy. RESULTS: There were no anastomotic leaks from the hand-sewn gastrojejunostomy. Operative times now are consistently 60 minutes or less, although the learning curve is quite long. Average hospital stay was 1.5 days. Average excessive weight loss was 69% at one and two years and 62% at three years. Overall complication rate was 14.8%. Perioperative death rate was 0.2%. CONCLUSIONS: The laparoscopic gastric bypass is a viable alternative to traditional open techniques. It is as safe and effective and can be performed with equal or greater efficiency. Adoption of hand-suturing techniques helps to improve the surgeon's skill and ability to cope with the occasional stapler misfire or complication.
Four term neonates presented with symptoms such as jitteriness and necrotising enterocolitis after paroxetine exposure in utero.
BACKGROUND: It is common for bariatric patients to experience postoperative nausea, depression and remorse for several months following surgery. Difficulty exists for the surgeon in delineating the physical from the psychological in treating these patients. Preoperative education, evaluation and preparation, although essential, will not identify nor eliminate all potential problems. METHODS: We report the case history of a patient who ultimately underwent reversal of her gastric bypass. Her symptoms required multiple procedures and hospital admissions for what appeared to be anatomical problems. All procedures were done laparoscopically. RESULTS: The patient's main complaints of persistent nausea and abdominal pain combined with radiographic evidence of sub-optimal anatomic construct led to multiple operative procedures. Psychological intervention relative to the persistent nausea and abdominal pain was ineffectual, although the supportive and consistent nature of the psychotherapy relationship was useful in overall patient stability and emotional well being. Complete reversal of the bypass did not effect improvement. Ultimately, the diagnosis of narcotic withdrawal prompted the institution of methadone treatment with complete cessation of the symptoms of nausea and pain. CONCLUSIONS: The diagnosis of narcotic withdrawal syndrome can be difficult in the postoperative bariatric patient. Psychological evaluation and support are essential elements of the program throughout the entire course of a patient's treatment experience. Laparoscopic techniques simplified the surgical care of this patient.
The molecular events triggered by MHC recognition and how they lead to the emergence of mature CD4 and CD8 lineage thymocytes are not yet understood. To address these questions, we have examined what signals are necessary to drive the development of CD8 lineage thymocytes in TCRalpha(-) mice in which TCR/MHC engagement cannot occur. We find that the combination of constitutive Notch activity and constitutive Bcl-2 expression are necessary and sufficient to allow the appearance of mature CD8 lineage thymocytes in TCRalpha(-) mice. In addition, Notch activity alone in TCRalpha(-) mice can induce the up-regulation of HES1, suggesting that thymocytes are competent to respond to Notch signaling in the absence of MHC recognition. These data indicate that survival and lineage commitment represent distinct, parallel pathways that occur as a consequence of MHC recognition, both of which are necessary for the development of mature CD8 lineage T cells.
The potential role of hepatocyte growth factor (HGF) in regulating extracellular matrix in mouse mesangial cells (MMC) was evaluated. Functional HGF receptors were deed in MMC by HGF-induced extracellular acidification, a response that was inhibited by the HGF inhibitor HGF/NK2, a splice variant expressing the N-terminal domain through the second kringle domain HGF also increased fibronectin and collagen alpha1 (IV) mRNA levels in these cells; the increases were associated with a concentration-dependent increase in transcriptional activity of the collagen alpha1 (IV) gene. HGF also stimulated fibronectin and collagen alpha1 (IV) mRNA levels in primary rabbit proximal tubule epithelial cells To evaluate the potential consequences of chronic elevation of HGF on renal fuction, HGF was administered continuously for 18 days to normal and diabetic C57BLKS/J lepr(db) mice. In the diabetic mice, HGF reduced creatinine clearance and increased microalbuminuria, indicating that chronic exposure to HGF impairs renal function. Thus, chronically elevated HGF may contribute to the progression of chronic renal disease in diabetes by decreasing the glomerular filtration rate and possibly promoting the accumulation of extracellular matrix.
HYPOTHESIS: A technique of the laparoscopic Roux-en-Y gastric bypass can be developed that is safe, effective, and practical in the community setting. DESIGN: A case series of 400 morbidly obese and superobese individuals who underwent the laparoscopic Roux-en-Y gastric bypass over a 22-month period. SETTING: Community private practice in Fresno, Calif. PATIENTS: A consecutive sample of 400 patients (70 males and 330 females) who met National Institutes of Health criteria for recommendation of a bariatric procedure. Only patients who had a previous gastric or bariatric procedure were excluded from this sample. INTERVENTION: Laparoscopic Roux-en-Y gastric bypass with a hand-sewn gastrojejunal anastomosis. MAIN OUTCOME MEASURES: Weight loss, complications, length of hospital stay, successful completion of the operation, and operative times were measured. RESULTS: Open conversion was required in 12 patients (6 males and 6 females) and a secondary operation for incomplete division of the stomach was required in 2 patients early in the case series. Alternative exposure and fixation techniques greatly reduced these occurrences. There were 6 staple-line failures owing to a change in the manufacture of the instrument. There were no leaks at the gastrojejunal anastomosis, but 21 patients required endoscopic balloon dilation for significant stenosis. The average hospital stay was 1.6 days for the patients who underwent laparoscopy and 2.7 days for patients requiring open conversion. Average excessive weight loss was 69% at 12 months. Operative times are between 60 and 90 minutes. Other complications are described. CONCLUSION: The Roux-en-Y gastric bypass can be safely and effectively performed in the community setting using advanced laparoscopic techniques.
Systemic administration of the L-type calcium channel agonists +/-Bay K 8644 or FPL 64176 causes a characteristic pattern of motor dysfunction in normal C57BL/6J mice that resembles generalized dystonia. There is no associated change in the electroencephalogram, confirming that the motor disorder does not reflect epileptic seizures. However, the electromyogram reveals an increase in baseline motor unit activity with prolonged phasic discharges consistent with dystonia. The duration and severity of dystonia is dependent on the dose administered and the age of the animal at testing. The effects are transient, with the return of normal motor behavior 1-4 hours after treatment. Similar effects can be provoked by intracerebral administration of small amounts of the drugs, indicating a centrally mediated response. Dystonia can be attenuated by co-administration of dihydropyridine L-type calcium channel antagonists (nifedipine, nimodipine, and nitrendipine) but not by non-dihydropyridine antagonists (diltiazem, verapamil, and flunarizine). These results implicate abnormal function of L-type calcium channels in the expression of dystonia in this model.
BACKGROUND: The Roux-en-Y gastric bypass (RYGBP) is one of the most common operations for morbid obesity. Laparoscopic techniques have been reported, but suffer from small numbers of patients, longer operative times and seemingly higher initial complication rates as compared to the traditional "open" procedure. The minimally invasive approach continues to be a challenge even to the most experienced laparoscopic surgeons. The purpose of this study is to describe our experience and complications of the laparoscopic Roux-en-Y gastric bypass with a totally hand-sewn gastrojejunostomy. METHODS: 1,040 consecutive laparoscopic procedures were evaluated prospectively. Only patients who had a previous open gastric procedure were excluded initially. Eventually, even patients with failed "open" bariatric procedures and other gastric procedures were revised laparoscopically to the RYGBP. All patients met NIH criteria for consideration for weight reductive surgery. RESULTS: There were no anastomotic leaks from the hand-sewn gastrojejunostomy. Early complications and open conversions were related to sub-optimal exposure and bowel fixation techniques. Several staple failures were attributed to a manufacturer redesign of an instrument. Average hospital stay was 1.9 days for all patients and 1.5 days for patients without complications. Operative times consistently approach 60 minutes. Average excess weight loss was 70% at 12 months. There were 5 deaths: perioperative pulmonary embolism (1), late pulmonary embolism (2), asthma (1), and suicide (1). CONCLUSIONS: The laparoscopic Roux-en-Y gastric bypass for morbid obesity with a totally hand-sewn gastrojejunostomy can be safely performed by the bariatric surgeon with advanced laparoscopic skills in the community setting. Fixation and closure of all potential hernia sites with non-absorbable sutures is essential. Stenosis of the hand-sewn gastrojejunal anastomosis is amenable to endoscopic balloon dilation. Meticulous attention must be paid to the operative and perioperative care of the patient.