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Biomedical subjects

R Sidhu

Publications and source records attributed to R Sidhu.

At least 19 recordsLinked to original sources
PubMed2006

Capsule endoscopy: an alternative to duodenal biopsy for the recognition of villous atrophy in coeliac disease?

BACKGROUND: Villous atrophy present on a duodenal biopsy remains the 'gold standard' diagnostic test for coeliac disease. However, endoscopic biopsy may cause morbidity and discomfort. Our aim was to evaluate wireless capsule endoscopy as an alternative test for the recognition of villous atrophy. METHOD: Twenty-one patients with a positive endomysial antibody referred for endoscopy and duodenal biopsy were also offered a wireless capsule endoscopy to evaluate their small bowel. Concurrently, other patients (n=23) referred for a wireless capsule endoscopy acted as controls. Wireless capsule endoscopy reports were assessed for the presence of villous atrophy by one blinded investigator. RESULTS: Twenty endomysial antibody positive patients subsequently had villous atrophy on duodenal biopsy. The controls all had normal duodenal biopsies (with a negative endomysial antibody) and no evidence of villous atrophy noted on their wireless capsule endoscopy. Of the 20 endomysial antibody positive patients with confirmed villous atrophy on biopsy, 17 had villous atrophy also detected by wireless capsule endoscopy. The sensitivity, specificity, positive and negative predictive values for wireless capsule endoscopy recognising villous atrophy were 85%, 100%, 100%, 88.9%, respectively. CONCLUSION: Wireless capsule endoscopy may be an option to recognise villous atrophy in patients with a positive endomysial antibody who are unwilling, or unable to have a gastroscopy. However, a negative test should be followed by a biopsy if coeliac disease is to be excluded.

Adult↗
PubMed2004

Bereavement support for families following the death of a child from cancer: practice characteristics of Australian and New Zealand paediatric oncology units.

OBJECTIVE: The impact of childhood cancer on the patient and family is devastating and results in significant emotional and physical effects on the child and family. An increasing awareness of the role of health care professionals at this time has led to the development of hospital-based bereavement support services. However, many services are not evidence based, and family support varies between institutions. The objective of this study was to determine current practice relating to hospital-based bereavement support programmes. METHODS: A survey of all major tertiary paediatric oncology units in Australia and New Zealand (N = 10) was undertaken. The survey instrument consisted of a 19-item questionnaire with open-ended and closed questions. RESULTS: Nine hospitals (90%) participated. Most hospitals provided a multidisciplinary bereavement service for approximately one year after a child's death. Programmes varied, but the most common hospital-based supports provided were counselling and support groups. Important findings were: a significant number of hospitals worked from a limited theoretical basis and understanding, did not screen for high risk of complicated grieving, did not formally evaluate their programme, and identified areas of unmet needs. CONCLUSION: The majority of paediatric oncology units in Australia and New Zealand provide dedicated multidisciplinary bereavement support services. There is variation in services provided, often due to a lack of resources and staffing. Findings indicate a need to further develop bereavement programmes, improve staff education and support, and increase the availability of resources in this area. Future research should explore the needs of bereaved families, as well as the range of services and evaluation methods that could be implemented as the baseline for 'best practice' hospital-based bereavement programmes.

Australia↗
PubMed2002

Cerebrospinal fluid pseudocyst of the breast.

Cerebrospinal fluid pseudocyst of the breast is a rare complication of ventriculoperitoneal shunt placement. Two cases of cerebrospinal pseudocyst of the breast are reported here. The mammography and ultrasound findings in these two cases are described.

Cerebrospinal Fluid↗
PubMed2001

Sonographic diagnosis of a solitary intramuscular cysticercal cyst.

We present a rare case of a solitary cysticercal cyst that involved the anterior abdominal wall musculature and was diagnosed with sonography. Sonograms revealed a small, well-defined, elliptical cystic lesion with an eccentric hyperechoic area within it. An eccentric, echogenic, pedunculated structure was seen within the cystic area of the lesion. No calcification was apparent. The lesion was surrounded by inflammation in the muscle. Hypervascularity in the surrounding muscle was noted on color Doppler imaging. If lesions with similar morphologic characteristics are encountered in the musculature or subcutaneous tissues during sonographic examination for another condition, one should suspect cysticercosis.

Abdominal Muscles↗
PubMed2001

L-cysteine and sodium hydrosulphide inhibit spontaneous contractility in isolated pregnant rat uterine strips in vitro.

The control of myometrial contractility during pregnancy and parturition is not fully understood. Gas signalling molecules, such as nitric oxide and carbon monoxide, have been shown to relax the myometrium and may be involved in the control of contractility. Hydrogen sulphide has recently been shown to be produced endogenously in animal and human tissue and to have a signalling function. The aim of the study was to investigate the effect of L-cysteine and sodium hydrosulphide, potential hydrogen sulphide donors, on pregnant rat uterine contractility in vitro. Strips of pregnant rat uterus (n=22) were set up in a standard organ bath system. Following equilibration and recording of spontaneous contractility, the tissue was exposed to 45 mM potassium chloride followed by 1 nM oxytocin. Dose ranges of 10(-8) - 10(-3) M of L-cysteine (n=8) or sodium hydrosulphide (n=8) were subsequently applied to the tissue. In a third series of experiments (n=6) the effect of doses of 10(-9), 10(-6) and 10(-3) M of L-cysteine, D-cysteine, L-serine, DL-methionine and DL-homocysteine on myometrial contractility were compared. Contractions were integrated over 10 min. periods and the values were compared by one-way analysis of variance. L-Cysteine and sodium hydrosulphide produced significant dose-dependent decreases in uterine spontaneous contractility. Of the amino acids tested, only L-cysteine produced a significant reduction in spontaneous contractility at a dose of 10(-3) M. This study has demonstrated novel tocolytic actions of L-cysteine and sodium hydrosulphide, however further work is required to determine their mechanisms of action.

Animals↗
PubMed2001

Sonographic diagnosis of diastematomyelia in utero: a case report and literature review.

Fetal diastematomyelia is a rare form of spinal dysraphism that is characterized by a complete or incomplete division of the spinal cord by an osseous or fibrocartilaginous septum. A case of diastematomyelia, which was detected on the routine third trimester detailed ultrasound scan, is presented. The diagnosis was based on the detection of an echogenic focus in the posterior aspect of the spine in association with widening of the interpedicular vertebral space. The case illustrates that diastematomyelia can occur in the absence of overt spina bifida and that prenatal detection will allow timely postnatal investigation and treatment. Prenatal literature is further reviewed to assess the clinical significance of this finding.

Adult↗
PubMed2001

Intrathoracic kidney in an adult.

An intrathoracic kidney, although rare, should be considered in a patient with a mass at the base of the lung on a chest radiograph. Excretory urography is diagnostic and may eliminate the need for further extensive investigation and operation.

Adult↗
PubMed2001

Lack of correlation between in vitro inhibition of CYP3A-mediated metabolism by a PPAR-gamma agonist and its effect on the clinical pharmacokinetics of midazolam, an in vivo probe of CYP3A activity.

RG 12525 (2-[[4-[[2-(1H-tetrazole-5-ylmethyl)phenyl]methoxy]phenoxy]methyl] quinolone) is a novel peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist. In vitro microsomal inhibition assays indicated that RG 12525 is a potent inhibitor of CYP3A4, with a Ki value of 0.5 microM. With the conservative assumption that the total plasma concentration of drug was available to metabolic enzymes following RG 12525 oral administration, marked inhibition of CYP3A4 was expected to substantially reduce the systemic clearance of compounds metabolized by this enzyme. The possibility also existed for inhibition of intestinal and hepatic CYP3A4 by RG 12525 to reduce "first-pass" metabolism and increase absolute bioavailability of CYP3A4 substrates orally coadministered. Consequently, an in vivo drug-drug interaction study was performed to evaluate the effects of orally administered RG 12525 on in vivo CYP3A4 activity in healthy male subjects. The pharmacokinetics of oral midazolam, a probe for intestinal and hepatic CYP3A activity, was not influenced by either the low (100 mg qd for 4 days) or high (600 mg qd for4 days) RG 12525 dosing regimen despite the resulting total plasma concentrations of inhibitor that were well above in vitro Ki values. The point estimates and 90% confidence intervals for the ratios of mean midazolam AUC for subjects administered 100 mg RG 12525 (110.6; 98.7-124.1) and 600 mg RG 12525 (98.4; 84.4-114.7) versus midazolam alone were within 80% to 125%. To explain these results, factors that could limit the accuracy of in vitro models in predicting metabolic drug interactions, mainly the high degree of RG 12525 protein binding (> 99.9%), were considered. The lack of correlation between the in vitro inhibition of CYP3A4 by RG 12525 and the inconsequential effects of this compound on midazolam pharmacokinetics accentuate the need to recognize factors other than plasma drug concentrations and potency of in vitro enzyme inhibition when extrapolating in vitro data to predict in vivo drug-drug interactions.

Adolescent↗
PubMed1999

Mismatch repair is diminished during stationary-phase mutation.

This paper is an invited Response to a recent Commentary [P.L. Foster, Rev. Mut. Res. 436 (1999) 179-184] entitled "Are adaptive mutations due to a decline in mismatch repair? The evidence is lacking". The Commentary argues that no evidence exists supporting the idea that mismatch repair is limiting specifically during stationary-phase mutation. A primary concern of the author is to question the method that we used previously to measure growth-dependent mutation. In this method, mutation rates are calculated using counts of mutant colonies taken at times when those colonies arise, rather than at a predetermined, fixed time. Here we show further data that illustrate why this must be done to ensure accurate mutation measurements. Such accuracy was necessary for our published determination that mismatch repair proteins are not limiting during growth-dependent mutation, but become so during stationary-phase mutation. We review the evidence supporting the idea that stationary-phase reversion of a lac frameshift mutation occurs in an environment of decreased mismatch repair capacity. Those data are substantial. The data presented in the Commentary, in apparent contradiction to this idea, do not justify the conclusion presented there.

Adenosine Triphosphatases↗
PubMed1997

Mismatch repair protein MutL becomes limiting during stationary-phase mutation.

Postsynthesis mismatch repair is an important contributor to mutation avoidance and genomic stability in bacteria, yeast, and humans. Regulation of its activity would allow organisms to regulate their ability to evolve. That mismatch repair might be down-regulated in stationary-phase Escherichia coli was suggested by the sequence spectrum of some stationary-phase ("adaptive") mutations and by the observations that MutS and MutH levels decline during stationary phase. We report that overproduction of MutL inhibits mutation in stationary phase but not during growth. MutS overproduction has no such effect, and MutL overproduction does not prevent stationary-phase decline of either MutS or MutH. These results imply that MutS and MutH decline to levels appropriate for the decreased DNA synthesis in stationary phase, whereas functional MutL is limiting for mismatch repair specifically during stationary phase. Modulation of mutation rate and genetic stability in response to environmental or developmental cues, such as stationary phase and stress, could be important in evolution, development, microbial pathogenicity, and the origins of cancer.

Adenosine Triphosphatases↗
PubMed1996

Endophytic taxol-producing fungi from bald cypress, Taxodium distichum.

Pestalotiopsis microspora occurs as a range of strains in bald cypress, Taxodium distichum. The organisms live as endophytes in the bark, phloem and xylem, and isolates show differences in cultural and microscopic characteristics on common laboratory media. Many of these fungi make taxol as determined by the reactivity of partially purified culture extracts with specific monoclonal antibodies against taxol. In the case of one strain of P. microspora (CP-4), taxol was isolated from culture medium and was shown to be identical to authentic taxol by chromatographic and spectroscopic means.

Antineoplastic Agents, Phytogenic↗
PubMed1993

Effects of ethanol on urinary acidification and on gluconeogenesis by isolated renal tubules.

Class I alcohol dehydrogenase (ADH) is present in the kidney of rats. Rats fed an alcohol-containing diet long-term had higher urinary pH and reduced titratable acidity compared with pair-fed controls; rates of ammonium excretion were unchanged. The effects of ethanol on the metabolism of isolated renal tubules were then studied. Gluconeogenesis from lactate, pyruvate, or glutamine was not inhibited by 10 mmol/L ethanol during 30- or 60-minute incubations, although there was a trend toward increased lactate/pyruvate ratios at 30 minutes in the presence of ethanol. When the medium was also supplemented with oleate, glucose synthesis from most substrates was decreased, and the addition of ethanol inhibited glucose synthesis dramatically. This interaction between oleate and ethanol was not abolished by 4-methylpyrazole, an inhibitor of ADH. This effect of ethanol was highly dependent on the concentration of oleate present in the medium and was not observed with palmitate or decanoate; the inhibition was reversed by increasing the medium concentration of albumin. We conclude that ethanol may mildly perturb the redox state of isolated kidney tubules without inhibiting glucose synthesis, and that ethanol and oleate interact to inhibit renal gluconeogenesis by a mechanism highly dependent on the fatty acid concentration. The mechanism by which ethanol in the diet reduces renal acid excretion remains unknown.

Amino Acids↗
PubMed1993

Dissociative effect of massed repetition on implicit and explicit measures of memory.

Subjects saw or heard words presented once, or repeated 4 or 16 times in massed fashion, and then received an implicit or explicit memory test. Massed repetition did not increase priming on word fragment completion beyond that obtained from a single presentation but did enhance performance on various explicit tests (free recall, recognition, question cued recall, and word fragment cued recall) and an implicit general knowledge test. Modality of presentation affected implicit and explicit word fragment cued tests but did not affect performance on any of the other tests. Levels of processing affected performance on implicit and explicit question cued tests. These results are consistent with a transfer appropriate processing account of dissociations among memory measures and imply that massed repetition promotes conceptual processing but does not entail a repetition of perceptual-based processes responsible for priming on word fragment completion.

Adult↗
PubMed1990

Osmotic regulation of methionine enkephalin in the posterior pituitary of the rat.

Methionine (Met) enkephalin is detectable in rat hypothalamic and neurointermediate lobe (NIL) tissue extracts using a specific radioimmunoassay. Reversed-phase HPLC revealed that only the pentapeptide form was present in the extracts. Total amounts of Met-enkephalin in extracts containing the median eminence (ME), supraoptic nucleus (SON), paraventricular nucleus (PVN), or NIL from control animals were 9.7 +/- 1.6, 0.9 +/- 0.2, 25.2 +/- 6.8 and 14.8 +/- 1.2 pmol respectively (means +/- S.E.M., n = 6). In animals given 340 mmol NaCl/l to drink for 5 days, no significant changes occurred in Met-enkephalin content in the SON or ME, but significant decreases were observed in the NIL and PVN (9.8 +/- 0.8 and 13.6 +/- 1.7 pmol, respectively). Amounts of Met-enkephalin in these tissues were further decreased after 12 days of 340 mmol NaCl/l (3.4 +/- 0.4 and 6.0 +/- 0.6 pmol). These data demonstrate that enkephalin immunoreactivity in the NIL is principally in the form of the Met-enkephalin pentapeptide, and that this peptide is released in response to increased plasma osmolality. The concomitant changes in the PVN and NIL tissue content suggest that the PVN is the source of NIL Met-enkephalin.

Animals↗
PubMed1989

Structure and expression of the rat class I alcohol dehydrogenase gene.

Clones containing the rat class I alcohol dehydrogenase (ADH) gene were isolated from a Charon 4A genomic library. The gene spans approximately 13 kb and comprises nine exons and eight introns. The upstream 436 bp contain canonical TATA and CCAAT sequences, an inverted CACCC box, a TG3 box found in mouse and human ADH promoters, and regions of homology to glucocorticoid response elements. The 5'-untranslated region of the ADH transcript has the potential to form a stable stem-loop structure. The first intron contains an unusual stretch of alternating purines and pyrimidines similar to that found in the same location in the mouse ADH gene. The amino acid insertion found in rat alcohol dehydrogenase results from a shift in the 3' splice junction of the fourth intron which adds an extra three base pairs to the fifth exon. Intron-exon boundaries are otherwise identical to those in mouse and human ADH genes. H4IIE cells stably transfected with plasmids containing the chloramphenicol acetyltransferase (CAT) gene fused behind the first 436 bp of the promoter region express CAT, but the CAT activity is not inducible by dexamethasone. The elements responsible for glucocorticoid stimulation of ADH gene transcription appear to reside outside of this region.

Alcohol Dehydrogenase↗