PubMed Health⌕ Search

Biomedical subjects

D Khoo

Publications and source records attributed to D Khoo.

14 recordsLinked to original sources
PubMed2004

Restless legs symptoms in thyroid disorders.

Dopaminergic dysfunction is associated with thyroid disorders and restless legs syndrome (RLS). In a 'face-to-face' interview, we evaluated for RLS using the diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG) in patients diagnosed biochemically with either hyper- or hypothyroidism, and in controls without thyroid disorders. Amongst 146 consecutive patients with biochemically confirmed thyroid disorders, none satisfied all the IRLSSG criteria of RLS, similar to the control population (0.2%, 1/434). However, we found 8.2% (12/146) with RLS-like symptoms (satisfied the first 3 IRLSSG criteria) compared to 0.9% (4/434) in the controls (p < 0.0001). Four (33.3%) of these patients reported complete resolution of these symptoms after treatment for their thyroid condition. In conclusion, while RLS-like symptoms were observed in some patients with thyroid disorders, our study demonstrates no significant difference of RLS prevalence between patients with thyroid disorders and euthyroid controls.

Adolescent↗
PubMed2001

Rigorous surveillance protocol increases detection of curable cancers associated with Barrett's esophagus.

Esophageal adenocarcinoma is increasing in incidence and has a high mortality unless detected early. Barrett's esophagus is the only known risk factor for this cancer; however, whether endoscopic surveillance reduces morbidity and mortality is controversial. Endoscopic cancer surveillance programes for Barrett's esophagus are not routinely practiced in the UK, and this is the first study to examine whether a rigorous surveillance protocol increases the detection rate of early oesophageal cancer. All patients with a diagnosis of Barrett's esophagus or associated adenocarcinoma attending Havering Hospitals NHS Trust between 1992 and 1998 were included. A retrospective analysis was made of patients undergoing informal surveillance (96 patients, 1992-1997) and a prospective analysis was conducted following the implementation of a rigorous protocol (108 patients, 1997-1998). Over the same time periods Barrett's associated cancers diagnosed in patients not undergoing surveillance were analyzed (262 patients 1992-1997, 98 patients 1997-1998). From 1992 to 1997, one case of high-grade dysplasia was detected (N = 96, 1%). From 1997 to 1998, two cancers and three high-grade dysplasias were detected during rigorous surveillance (N = 108, 4.6%). Three of these patients have had curative esophagectomies (one high-grade dysplasia and two T1,N0,M0 tumors). In 1992-1997, 10 patients were found to have cancer in previously undiagnosed Barrett's esophagus (N = 262, 3.8%). Of 3/10 cancers treated surgically, one patient had a curative procedure (T1,N0,M0). In 1997-1998, nine patients were found to have de novo Barrett's esophagus cancer (N = 88, 10.2%) and three had curative resections (T1,N0,M0). Two of the patients with T1 lesions had no endoscopic evidence of cancer but were detected as a result of the multiple biopsy protocol. In conclusion, a rigorous biopsy protocol increases the detection of early cancer in Barrett's esophagus.

Adenocarcinoma↗
PubMed2000

Vancomycin pharmacokinetics and Bayesian estimation in pediatric patients.

The vancomycin pharmacokinetic profile was characterized in six pediatric patients and the potential of nonlinear mixed effects modeling and Bayesian forecasting for vancomycin monitoring was explored using NONMEM V (1.1). Based on steady state serial vancomycin concentrations, the estimates of mean t1/2, Vd, and Cl derived by the Sawchuk and Zaske method (1) were 3.52 hours, 0.57 L/kg, and 0.12 L/h per kg, respectively. NONMEM analysis demonstrated that a weight-adjusted two-compartment model described individual patients' data better than a comparable one-compartment model. The two-compartment estimates of mean t1/2alpha, t1/2beta, Vss, and Cl were 0.80 hour, 5.63 hours, 0.63 L/kg, and 0.11 L/h per kg, respectively. The relatively long mean t1/2alpha suggests that peak vancomycin concentrations measured earlier than 4 hours postdose do not reflect postdistributional serum concentrations. NONMEM population modeling revealed that a weight-adjusted two-compartment model provided a better fit than a comparable one-compartment model. The resulting population parameters and variances were fixed in NONMEM to obtain Bayesian predictions of individual vancomycin serum concentrations. Bayesian estimation with either a single midinterval or trough sample has the potential to provide accurate and precise predictions of vancomycin concentrations. This should be evaluated using a vancomycin population pharmacokinetic model based on a larger sample of pediatric patients.

Anti-Bacterial Agents↗
PubMed2000

Inhibition of PKR activation by the proline-rich RNA binding domain of the herpes simplex virus type 1 Us11 protein.

Upon activation by double-stranded RNA in virus-infected cells, the cellular PKR kinase phosphorylates the translation initiation factor eukaryotic initiation factor 2 (eIF2) and thereby inhibits protein synthesis. The gamma 34.5 and Us11 gene products encoded by herpes simplex virus type 1 (HSV-1) are dedicated to preventing the accumulation of phosphorylated eIF2. While the gamma 34.5 gene specifies a regulatory subunit for protein phosphatase 1 alpha, the Us11 gene encodes an RNA binding protein that also prevents PKR activation. gamma 34.5 mutants fail to grow on a variety of human cells as phosphorylated eIF2 accumulates and protein synthesis ceases prior to the completion of the viral life cycle. We demonstrate that expression of a 68-amino-acid fragment of Us11 containing a novel proline-rich basic RNA binding domain allows for sustained protein synthesis and enhanced growth of gamma 34.5 mutants. Furthermore, this fragment is sufficient to inhibit activation of the cellular PKR kinase in a cell-free system, suggesting that the intrinsic activities of this small fragment, notably RNA binding and ribosome association, may be required to prevent PKR activation.

Animals↗
PubMed2000

A man with osteoblastic metastasis and hypocalcaemia.

We report a case of an 80-year-old man with osteoblastic metastases from advanced carcinoma of the prostate presenting with a grand mal seizure resulting from severe hypocalcaemia. He had low serum phosphate and ionised calcium levels, elevated serum skeletal alkaline phosphatase and intact parathormone levels. 99mTc radioisotope bone scan revealed a "super bone scan" suggestive of osteomalacia. The serum 1, 25-dihydroxycholecalciferol level was unexpectedly elevated. The biochemical abnormalities persisted despite high dose calcium replacement, but improved with supraphysiological doses of 1,25 (OH)2 vitamin D3 (Rocaltrol) therapy. We hypothesise that the hypocalcaemia in this patient was due to vitamin D resistance secondary to a humoral factor secreted by the tumour.

Aged↗
PubMed1998

Production of bioactive amino-terminal domain of the thyrotropin receptor via insertion in the plasma membrane by a glycosylphosphatidylinositol anchor.

A chimeric cDNA construct encoding the extracellular amino-terminal domain (ECD) of the thyrotropin receptor fused to the signal for addition of glycosylphosphatidylinositol from the Thy-1 gene directs efficient expression of the ECD at the plasma membrane of transfected CHO cells. A cell line (GT14) expressing over 106 receptors/cell was isolated, which allows direct detection, by flow cytometry, of autoantibodies from the majority of patients with Graves' disease or autoimmune idiopathic myxedema. Treatment of GT14 cells with a glycosylphosphatidylinositol-specific phospholipase C (PI-PLC) releases a soluble 80 kDa molecule which neutralizes the autoantibodies from Graves patients. Whereas it does not bind TSH when released from the cells by PI-PLC in free form, the soluble ECD displays clear TSH binding activity when it is released as a complex with a monoclonal antibody recognizing a conformational epitope of the ECD. Our results allow production of bioactive ECD of the thyrotropin receptor in high yield, with possible applications in structural analyses.

Amino Acid Sequence↗
PubMed1996

Ulnar nerve anatomy and compression.

Compression of the ulnar nerve can be understood in terms of the anatomic and dynamic factors. Although the ulnar nerve may be compressed at any point along its course, it is particularly susceptible at the elbow and the wrist. Clinically relevant anatomy will be reviewed in an attempt to provide the reader with a logical framework for successfully diagnosing and managing typical and atypical ulnar nerve compression lesions.

Humans↗
PubMed1994

Palliation of malignant intestinal obstruction using octreotide.

Vomiting due to malignant intestinal obstruction is an unpleasant terminal event in many cancer patients, which responds poorly to conventional therapies. Somatostatin and its long-acting analogues reduce intestinal secretion. For this reason, octreotide was used in a phase I/II study of patients with intractable vomiting secondary to intestinal obstruction due to malignant disease. Vomiting was controlled or the volume of nasogastric aspirate was markedly reduced in 18 of 24 (75%) patients receiving a subcutaneous infusion of octreotide (median initial dose 300, range 100-600 micrograms/day) for a median of 9.4 (range 1-38) days. A further 2 patients had partial relief of their symptoms. Octreotide is an effective treatment of nausea and vomiting due to malignant bowel obstruction.

Adult↗
PubMed1993

Endocrine disorders (parathyroid hormone).

In summary, precise PTH measurements have been difficult and complex as a result of low circulating concentrations of biologically active hormone and the immunoheterogeneity of circulating PTH molecules. The differences in secretion rates and metabolism of various PTH fragments in different clinical disorders further complicated the interpretation of various radioimmunoassable PTH levels. In recent years, the development of two-site or intact immunometric assays represents significant advancements in PTH measurement. These assays, for the first time, provide the long-awaited sensitivity and precision of PTH measurement. The IRMA assay has certainly overcome the difficulties in accurately diagnosing parathyroid disorders and the difficulties in the differential diagnosis of hypercalcemia. Above all, these assays are more convenient and more specific in patients with compromised renal function.

Calcium↗
PubMed1991

Subclinical varicocele: the effectiveness of varicocelectomy.

To investigate the controversial concept that subclinical varicoceles are detrimental to spermatogenesis, we undertook a prospective study of the effectiveness of surgery in 56 infertile men with clinical and subclinical varicoceles. Our statistical approach specifies improvement as a change from individual baseline level. The over-all variability in sperm counts precluded the demonstration of significant changes in sperm density consequent to surgery. Improvement in sperm motility was seen in both groups, being slightly greater in the subclinical group. The changes were inversely related to baseline levels and increased with time from surgery. Therefore, it appears that the detection of subclinical varicoceles may be warranted in infertile men with abnormal semen parameters.

Humans↗
PubMed1991

Screening assays for immunologic infertility: a comparison study.

Because the immunobead antisperm antibody test (IBT) is difficult to learn and results are heavily operator-dependent, we compared findings on IBT with those of SpermMAR and SpermCheck in 58 patients to determine whether the latter two tests could demonstrate improved screening ability. Assays performed on both sperm and serum (i.e., direct and indirect) yielded 100% positive predictive values when IBT was used as the standard. Both SpermCheck and SpermMAR are easier to perform, and, as the former has a slightly greater sensitivity, we recommend SpermCheck for the detection of immunologic infertility.

Autoantibodies↗
PubMed1991

Platelet-activating factor in sperm from fertile and subfertile men.

STUDY OBJECTIVE: To examine the proposed role of platelet-activating factor (PAF) as a mediator of sperm function first by quantitating the concentration of PAF in sperm and second by incubating sperm with PAF and assessing the change in sperm motion parameters with a computerized motion analysis system. DESIGN: Retrospective, case-control study. SETTING: University hospital urology clinic. PATIENTS: Concentrations of PAF were measured in sperm from 6 randomly chosen normal donors and 8 asthenozoospermic patients. The change in sperm motion parameters was assessed in sperm from 10 randomly chosen normal donors and 7 asthenozoospermic patients. RESULTS: Platelet-activating factor concentrations were significantly higher (P less than 0.05) in spermatozoa from asthenozoospermic patients (149 +/- 18.0 fmol/10(6) sperm) than in sperm from normal donors (91.9 +/- 13.0 fmol/10(6) sperm). Exogenous PAF did not enhance the percent motility of precapacitated or capacitated sperm from either patients or donors, and computerized semen analysis revealed no enhancement of sperm motion parameters in asthenozoospermic patients after addition of PAF to either precapacitated or capacitated sperm. CONCLUSION: Platelet-activating factor does not appear to have therapeutic value as a means of enhancing sperm motility.

Case-Control Studies↗