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Biomedical subjects

J Jeffery

Publications and source records attributed to J Jeffery.

At least 19 recordsLinked to original sources

Increased urinary dopamine excretion in association with bilateral carotid body tumours-- clinical, biochemical and genetic findings.

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an (123)I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than non-familial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient.

3-Iodobenzylguanidine↗

Bacteria fauna from the house fly, Musca domestica (L.).

The house fly, Musca domestica has long been considered a potential agent for disease transmission ever since its existence. The general truth of this assertion remains undisputed till the present day in spite of increasing awareness toward an improved sanitation and better hygiene. The habitual movement of house fly from filthy substrata such as human faeces, animal excreta, carcasses, garbage, etc. makes them ideal candidates for disease transmission such as cholera, shigellosis, salmonellosis and others when settling on food. Fly as a potential mechanical vector of pathogenic bacteria was elucidated in this study by examining flies from various breeding sites such as food courts, dumping ground, food processing areas and poultry farm in Peninsular Malaysia. The flies were baited with 10% sugar solution on a glass slide in the field. All materials used for collection of samples were sterile. Bacteria from fly sample were isolated using the normal isolation technique. Bacillus sp., Coccobacillus sp., Staphylococcus sp., Microccus sp., Streptococcus sp., Acinetobacter sp., Enterobacter sp., Proteus sp., Escherichia sp., Klebsiella sp. and yeast cells were isolated from feaces, vomitus, external surfaces and internal organs of house fly. Newly emerged house fly did not harbour any bacteria.

Animals↗

A comparative study of adult mosquito trapping using dry ice and yeast generated carbon dioxide.

Adult mosquito collections were conducted for 12 weeks in two residential areas in Kuala Lumpur. The CDC light traps were compared using dry ice and yeast as sources of carbon dioxide attractants for mosquitoes. The efficacy of the dry ice baited trap was significant over yeast generated CO2 trap. The predominant species obtained were Culex quinquefasciatus, Stegomyia albopicta and Armigeres subalbatus.

Aedes↗

Review of forensically important entomological specimens in the period of 1972 - 2002.

Forensic entomological specimens received by the Unit of Medical Entomology, IMR., from hospitals and the police in Malaysia in the last 3 decades (1972 - 2002) are reviewed. A total of 448 specimens were received. From these, 538 identifications were made with the following results: Eighteen species of cyclorrphaga flies were identified consisting of Chrysomya megacephala (Fabricius) 215 cases (47.99%), Ch. rufifacies (Masquart) 132 (29.46%), Ch. villeneuvi Patton 10 (2.23%), Ch. nigripes Aubertin 7 (1.56%), Ch. bezziana Villeneuve 4 (0.89%), Ch. pinguis (Walker) 1 (0.22%), Chrysomya sp. 47 (10.49%), Sarcophaga sp. 28 (6.25%), Lucilia sp. 21 (4.69%), Hermetia sp. 15 (3.35%), He. illucens (Linnaeus) 1 (0.22%), Hemipyrellia ligurriens (Wiedemann) 3 (0.67%), Hemipyrellia sp. 2 (0.45%), Ophyra spinigera 1 (0.22%), Ophyra sp. 6 (1.34%), Calliphora sp. 24 (5.36%), Synthesiomyia nudiseta (Wulp) 1 (0.22%) and Eristalis sp. 1 (0.22%). Other non - fly insect specimens are Pthirus pubis (Linnaeus) (Pubic louse) 2 (0.45%) and Coleoptera (Beetles) 1 (0.22%). Ch. megacephala and Ch. rufifacies were the commonest species found in cadavers from different ecological habitats. Sy. nudiseta is an uncommon species, thus far found only on cadavers from indoors. Sy. nudiseta is reported for the second time in Peninsular Malaysia. A total of 329 cases (73.44%) had a single fly infestation, 109 cases (24.33%) had double fly infestation and 10 cases (2.23%) had triple fly infestation. Five cases (1.12%) had eggs and 3 cases (0.67%) had larval stages that were not identifiable. No arthropods were retrieved from cadavers in 8 cases (1.79%). In conclusion, although large number of fly species were found on human cadavers, the predominant species are still those of Chrysomya.

Journal Article↗

One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study.

BACKGROUND: Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

Creatinine↗

Measurement of proteases using chemiluminescence-resonance-energy-transfer chimaeras between green fluorescent protein and aequorin.

Homogeneous assays, without a separation step, are essential for measuring chemical events in live cells and for drug discovery screens, and are desirable for making measurements in cell extracts or clinical samples. Here we demonstrate the principle of chemiluminescence resonance energy transfer (CRET) as a homogeneous assay system, using two proteases as models, one extracellular (alpha-thrombin) and the other intracellular (caspase-3). Chimaeras were engineered with aequorin as the chemiluminescent energy donor and green fluorescent protein (GFP) or enhanced GFP as the energy acceptors, with a protease linker (6 or 18 amino acid residues) recognition site between the donor and acceptor. Flash chemiluminescent spectra (20--60 s) showed that the spectra of chimaeras matched GFP, being similar to that of luminous jellyfish, justifying their designation as 'Rainbow' proteins. Addition of the protease shifted the emission spectrum to that of aequorin in a time- and dose-dependent manner. Separation of the proteolysed fragments showed that the ratio of green to blue light matched the extent of proteolysis. The caspase-3 Rainbow protein was able to provide information on the specificity of caspases in vitro and in vivo. It was also able to monitor caspase-3 activation in cells provoked into apoptosis by staurosporine (1 or 2 microM). CRET can also monitor GFP fluor formation. The signal-to-noise ratio of our Rainbow proteins is superior to that of fluorescence resonance energy transfer, providing a potential platform for measuring agents that interact with the reactive site between the donor and acceptor.

Aequorin↗

Neointimal and tubulointerstitial infiltration by recipient mesenchymal cells in chronic renal-allograft rejection.

BACKGROUND: Tissue remodeling depends on mesenchymal cells (fibroblasts and myofibroblasts) and is a prominent feature of chronic renal-transplant rejection. It is not known whether the mesenchymal cells that participate in remodeling originate locally or from circulating precursor cells. METHODS: We obtained biopsy specimens of renal allografts from six male recipients of an allograft from a female donor, four female recipients of an allograft from a male donor, two male recipients of an allograft from a male donor, and two female recipients of an allograft from a female donor. All the allografts were undergoing chronic rejection. All but two specimens were obtained within six months after transplantation. We used immunohistochemical methods to identify mesenchymal cells with smooth-muscle alpha-actin and in situ hybridization to identify mesenchymal cells with Y-chromosome DNA. RESULTS: No Y-chromosome bodies were identified in the case of the two renal-allograft specimens in which both the donor and the recipient were female. In the case of the two renal-allograft specimens in which both the donor and the recipient were male, approximately 40 percent of mesenchymal cells contained a Y-chromosome body. In the case of the six specimens in which the donor was female and the recipient was male, a mean (+/-SD) of 34+/-16 percent of mesenchymal cells in the neointima, 38+/-12 percent of such cells in the adventitia, and 30+/-7 percent of such cells in the interstitium contained the Y-chromosomal marker, indicating that they originated from the recipient rather than the donor. In the case of the four renal-allograft specimens in which the donor was male and the recipient was female, the respective values were 24+/-15 percent, 33+/-9 percent, and 23+/-8 percent, indicating a persistent population of donor mesenchymal cells. CONCLUSIONS: The presence of mesenchymal cells of host origin in the vascular and interstitial compartments of renal allografts undergoing chronic rejection provides evidence that a circulating mesenchymal precursor cell has the potential to migrate to areas of inflammation.

Actins↗

Long-term allograft surveillance: the role of protocol biopsies.

The safety of the renal allograft biopsy and the standardization of allograft histopathology interpretation have renewed interest in the performance of protocol (surveillance) biopsies. Recent surveillance biopsy studies in the areas of pre-implantation and in the early and late post-transplant periods are discussed.

Biopsy↗

Colchicine induced rhabdomyolysis.

A case of colchicine induced rhabdomyolysis is reported. A 73 year old man with ischaemic heart disease, atrial fibrillation, chronic congestive cardiac failure, and chronic gout presented with diffuse muscle pain. He had been taking an increased dose of colchicine (1.5 mg daily) for an exacerbation of gout for six weeks before the presentation. Investigations confirmed the diagnosis of rhabdomyolysis and discontinuation of colchicine resulted in resolution of clinical and biochemical features of rhabdomyolysis. Although neuromuscular adverse effects of colchicine are well recognised, rhabdomyolysis is rare and this is only the fourth reported case of colchicine induced rhabdomyolysis in the literature.

Aged↗

Ascitic fluid analysis: the role of biochemistry and haematology.

In specific settings, biochemical and haematological analysis of ascitic fluid may provide answers to important clinical questions. This review seeks to outline the value and limitations of ascitic fluid analysis and the main clinical scenarios in which it may be useful.

Ascites↗

Apoaequorin monitors degradation of endoplasmic reticulum (ER) proteins initiated by loss of ER Ca(2+).

Apoaequorin was targeted to the cytosol, nucleus, and endoplasmic reticulum of HeLa cells in order to determine the effect of Ca(2+) release from the ER on protein degradation. In resting cells apoaequorin had a rapid half-life (ca. 20-30 min) in the cytosol or nucleus, but was relatively stable for up to 24 h in the ER (t(1/2) > 24 h). However, release of Ca(2+) from the ER, initiated by the addition of inhibitors of the ER Ca(2+)/Mg(2+) ATPase such as 2 microM thapsigargin or 1 microM ionomycin, initiated rapid loss of apoaequorin in the ER, but had no detectable effect on apoaequorin turnover in the cytosol nor the nucleus. This loss of apoprotein was not the result of secretion into the external fluid, and could not be inhibited by inhibitors of protein degradation by proteosomes. Proteolysis of apoaequorin in cell extracts (t(1/2) < 20 min) was completely inhibited in the presence of 1 mM Ca(2+), and this effect was independent of the ER retention signal KDEL at the C-terminus. Proteolysis was unaffected by the presence of selected serine protease inhibitors, or 10 microM Zn(2+), a known caspase-3 inhibitor. The results show that apoaequorin can monitor proteolysis of ER proteins activated by loss of ER Ca(2+). Several Ca(2+)-binding proteins exist in the ER, acting as the Ca(2+) store and chaperones. Our results have important implications both for the role of ER Ca(2+) in cell activation and stress and when using aequorin for monitoring free ER Ca(2+) over long time periods.

Aequorin↗

Protocol biopsies in the management of renal allograft recipients.

The safety of the renal allograft biopsy and the standardization of allograft histopathology interpretation have renewed interest in the protocol biopsy. Recent studies in the areas of 'marginal' donors, surveillance of acute rejection, molecular biology and chronic rejection are discussed.

Biopsy↗

Comparative multicentre study of a panel of thyroid tests using different automated immunoassay platforms and specimens at high risk of antibody interference.

The introduction of automation for immunoassays in recent years has brought about important and evident improvements in assay precision. Increasing standardization and comparability between platforms should enable the development of clinical guidelines and diagnostic algorithms for appropriate clinical decision making. A continuing source of variation between different automated immunoassay platforms is the sporadic effect of interfering antibodies or substances, thus causing aberrant results not supporting the patient's clinical status. The aim of this study was to describe current thyroid panel variation between automated immunoassay platforms including population specimens at risk of antibody interference. A multisite design with laboratories in three different countries using four different automated immunoassay platforms (Roche-Boehringer Mannheim Elecsys (Italy), Roche-Boehringer Mannheim ES300 (Wales), Bayer Immuno 1 and the Bayer ACS:180 evaluated the thyroid panel of thyrotropin (TSH), triiodothyromine (T3), free thyroxine (FT4) and free triiodothyronine (FT3). A common set of 158 randomly selected patient samples of non-thyroid and thyroid disorders, with and without treatment, was tested. Included were 62 patient samples at risk for endogenous antibody interference with high antimicrosomal antibody, anti-TSH receptor antibody and increased rheumatoid factor sub-populations. Across all controls and between platforms, precision measurements were comparable and varied between 0.7% and 12.8% for TSH, 2.8% and 13% for FT4, 1.8% and 10.5% for FT3 and 3.1% and 16% for T3 assay. Acceptable correlation and reproducibility were found between the three Bayer Immuno 1 platforms at each country's site with all four thyroid panel assays demonstrating r-values of 0.989 to 1.000 and slopes of 0.915 to 1.078. Comparisons between the different platforms showed acceptable correlation for all thyroid panel assays. Specimens containing rheumatoid factor were associated with a significantly increased variation between systems for the FT4 and FT3 assays (p < 0.01). This effect did not appear to be selective for a given platform. For specimens with raised autoimmune antibodies and therefore at risk of assay antibody interference, no variation could be observed between the platforms.

Antibodies↗

Subclinical rejection--a potential surrogate marker for chronic rejection--may be diagnosed by protocol biopsy or urine spectroscopy.

Our studies of protocol biopsy studies have shown that normal allograft histology can not be assumed by crude tests of renal function such as the serum creatinine concentration, and that there is a high prevalence of subclinical rejection in the first 6 months post-transplant (7, 13-17). The apparent ability of urine MR and IR spectra to reliably identify patients with normal allograft histology, if confirmed in a larger database, will preclude the need for a protocol biopsy in approximately 20-50% of patients. Conversely, finding urine MR or IR spectra characteristic of subclinical rejection would provide the opportunity for early treatment. The clear separation between patients with normal histology from those with subclinical rejection can be attributed to the use of the whole urine spectrum to develop the classifiers. Additional advantages of using MR or IR spectra of urine as a diagnostic tool compared to the biopsy include simplicity (i.e. no processing is required), low cost, rapid turnaround (i.e. < 15 minutes/sample), and, particularly, low risk, thus allowing for repetitive sampling. The ability to non-invasively diagnose acute inflammation in the kidney would be of great assistance in the post-transplant monitoring of renal transplant patients. Indeed, by following subclinical inflammation as detected in the MR/IR spectra it will be possible to tailor the intensity of the immunosuppression to the inflammatory status of the graft, thus minimising the risks of both insufficient and excessive immunosuppression. Furthermore, by following subclinical inflammation, as detected in the MR/IR spectra, it will be possible to test the hypothesis that subclinical rejection (i.e. persistence of its MR/IR spectral classifier) is a surrogate marker for the development of chronic rejection.

Acute Disease↗

Quantitation of allograft fibrosis and chronic allograft nephropathy.

Despite improvements in the prevention and treatment of acute renal allograft rejection, the long-term survival of renal transplants has not increased. Immunologic and non-immunologic factors contribute to the gradual deterioration of graft function and to the histologic lesion characterized by vascular and interstitial fibrosis ('chronic rejection'). Quantitation of this process has been attempted using various invasive and non-invasive methods. These methods, performed at different times post-transplant, are reviewed in this article. In particular, pathology scoring systems and the potential of using computerized image analysis of biopsy material are discussed.

Biopsy↗