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Biomedical subjects

D F Griffiths

Publications and source records attributed to D F Griffiths.

At least 19 recordsLinked to original sources
PubMed1994

Quantitative audit of the content of histopathology reports.

An audit of histopathology reports presents the problem that the output is textual and difficult to quantify. This makes the definition of an adequate report subjective and susceptible to observer variation. A procedure has been developed which allows the quantitative analysis of reports and facilitates the development of local reporting guidelines. A topic is selected; the auditor then lists the possible details that may be included in the report and notes how many reports from a sample include each detail. The results are discussed at a departmental meeting with the aim of agreeing on reporting guidelines. At a later date another sample of reports can be analysed for compliance with the guidelines and compared with the previous reports. Problems with compliance can be discussed further and at the audit meeting the guidelines may be amended appropriately, thus completing the audit cycle. This method of audit has the advantage that the results are quantitative and that the group discussion and re-examination of the guidelines has educational value.

Humans↗
PubMed1994

Permselectivity in thin membrane nephropathy.

The glomerular permselectivity to polydisperse neutral dextrans was compared in 6 patients with thin membrane nephropathy (TMN) and 10 healthy controls. Despite having normal renal hemodynamics and minimal proteinuria, the patients with TMN had significantly increased fractional clearance of neutral molecules with Stokes radius > 42 A. Conventional theories of glomerular barrier size selectivity cannot fully explain these data since they would predict that our patients would have had nephrotic range proteinuria.

Adult↗
PubMed1993

Low-dose cyclosporin nephrotoxicity in the rat.

The nephrotoxicity of cyclosporin (CsA) continues to be a clinical problem that detracts from its obvious benefits as an immunosuppressive agent. Animal models designed to study the problem have generally relied either on chronic administration of high doses of the drug or acute administration of single i.v. doses. The present study establishes a model of CsA nephrotoxicity using doses of the drug comparable to those used in man administered over a time period sufficient for haemodynamic and structural changes to become evident. The technique used measures glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) by the plasma clearance of chromium EDTA and iodohippuran respectively. This has the advantage of allowing sequential measurements in individual animals. Significant impairment of GFR was seen in animals treated intraperitoneally with doses of CsA as low as 5 mg/kg/day. CsA 7.5 mg/kg/day caused a significant reduction in ERPF, and at 10 mg/kg/day and greater filtration fraction also declined significantly. Detailed histological examination of the kidneys from these animals also revealed significant tubular dilatation at 10 mg/kg/day and above. This model of CsA toxicity circumvents many of the problems associated with other models. The animals can be studied longitudinally and the period of administration has relevance to clinic practice. This work provides the basis for further studies which can closely mimic the clinical situation using doses similar to those used for human maintenance immunosuppression.

Animals↗
PubMed1992

Renal transplant sonography: correlation of Doppler and biopsy results in cellular rejection.

Seventy-one patients with allograft dysfunction had concomitant Doppler sonography and percutaneous biopsy. Forty-one had biopsy proven acute cellular rejection and eight had acute cellular rejection in combination with acute tubular necrosis. Real time ultrasonic appearance and various parameters of Doppler waveform were studied and compared with 30 controls who had a long period of stable function with no previous episodes of rejection or acute tubular necrosis (ATN). Morphological appearances were unhelpful in diagnosing rejection. A resistive index greater than 0.8 in the study group was highly specific for dysfunction but could not differentiate between acute rejection and ATN. However, two patients in the control group of normal transplants had a resistive index of 0.83. An early to mid diastolic notch was highly specific for acute rejection but of low sensitivity. It may be the only Doppler indication of cellular rejection and may be present when the resistive index is in the normal range.

Adolescent↗
PubMed1992

Selective IgA deficiency associated with glomerulonephritis and oligoarthritis.

A 59 year old woman with selective IgA deficiency associated with oligoarthritis and glomerulonephritis is described. She was seropositive for rheumatoid factor and renal histological examination showed a focal glomerulonephritis. High titre rheumatoid factor and a focal glomerulonephritis were also present in the only other well documented report of selective IgA deficiency and renal disease. Histological examination of the kidney suggested that the glomerulonephritis was mediated by immune complexes.

Antigen-Antibody Complex↗
PubMed1991

Rationalisation of follow-up in patients with non-invasive bladder tumours. A preliminary report.

The risk of recurrence and progression in 170 patients presenting with pTa urothelial tumours of the bladder has been estimated so that follow-up can be rationalised. Patients were followed up for between 1 and 15 years, the original pathology reviewed and those with carcinoma in situ (CIS) or dysplasia of the background urothelium excluded. Only 5 patients progressed over the whole follow-up period, giving an overall progression rate of 3%. Solitary tumours had an annual initial recurrence risk (AIR) of 0.23 in the first year; after the first year the AIR fell to approximately 0.1 but did not fall significantly in subsequent years up to 8 years. Of the 45 patients with multiple tumours, 32 suffered recurrences within the first year (AIR 0.71). Tumour grade did not influence either recurrence or progression. The results indicate that for solitary pTa tumours, less frequent endoscopic follow-up is justified but some continued surveillance after 5 disease-free years is necessary. The estimated risk of recurrence is a useful factor to consider when planning follow-up.

Adult↗
PubMed1989

The morphological and immunohistochemical analysis of renal biopsies by light and electron microscopy using a single processing method.

A methodology is described in which a number of well-established research techniques are brought together to enable the complete diagnostic analysis of a renal biopsy on a single piece of tissue. By embedding the biopsy in the acrylic resin LR White, unsupported sections of which are stable in the electron beam, light and electron microscopy and immunocytochemistry become feasible on sections from the same block. The biopsy is glutaraldehyde fixed but post-fixation in osmium tetroxide, which is often deleterious to antigen preservation, is omitted. Extraction in organic solvents and resin monomer is minimized by rapidly infiltrating the tissue from 70% ethanol and polymerizing the resin catalytically at 0 degrees C. Semithin sections can be stained with haematoxylin and eosin, Toluidine Blue or methenamine silver, giving results similar or superior to those obtained from paraffin sections. Thin sections show that the standard of morphological preservation is similar to that seen using epoxide sections even though the kidney is unosmicated. The tissue retains a high level of antigen reactivity, which, in the limited number of cases so far examined, has paralleled or exceeded that demonstrated by conventional immunofluorescence on frozen sections.

Biopsy↗
PubMed1989

Duplex Doppler ultrasound in the diagnosis of acute renal allograft rejection.

As renal transplantation becomes more commonplace and successful, there is an increasing demand for non-invasive methods of studying possible complications. One hundred and fifty-four duplex Doppler sonography scans were performed in 38 patients within 52 days of receiving a renal allograft. Renal vascular impedance was estimated in the intrarenal arteries by calculating the resistive index ([peak systolic frequency shift--lowest diastolic frequency shift]/peak systolic frequency shift). A resistive index of greater than 0.80 was very suggestive of rejection (positive predictive value 82%); with a value of less than 0.70 rejection was unlikely (negative predictive value, 98%).

Adolescent↗
PubMed1988

Demonstration of somatic mutation and colonic crypt clonality by X-linked enzyme histochemistry.

Cellular mosaicism resulting from X-chromosome inactivation in heterozygous females can be shown histochemically; using this approach we have demonstrated age-related gene reactivation and tumour clonality. We now show in female mice heterozygous for reduced expression of glucose-6-phosphate dehydrogenase (G6PD) activity that colonic epithelial cells express either normal or low enzyme activity, and form patches composed of multiple crypts of uniform phenotype. We also show that a low-enzyme colonic epithelial cell phenotype can be induced in normal mice by carcinogen treatment, these cells again occur in patches, but are restricted to scattered single crypts, the frequency of which is related to treatment. A small proportion of colonic tumours in carcinogen treated normal mice are also of low-enzyme phenotype. We conclude that we have visualized the effects of a sporadic carcinogen induced somatic mutation in the G6PD gene of crypt stem cells and that a single stem cell maintains each colonic crypt. This inducible defective activity of a ubiquitous 'housekeeping' enzyme provides a somatic clonal marker system of wide potential application.

Animals↗
PubMed1987

Duodenal carcinoid tumours, phaeochromocytoma and neurofibromatosis: islet cell tumour, phaeochromocytoma and the von Hippel-Lindau complex: two distinctive neuroendocrine syndromes.

To clarify neuroendocrine syndromes we have reviewed the association of neurofibromatosis with carcinoid tumours and of neurofibromatosis, phaeochromocytoma or von Hippel-Lindau complex with either carcinoid or islet cell tumours. In nine cases of neurofibromatosis with a carcinoid tumour studied all carcinoid tumours were in the duodenum, were distinctive histologically and had widespread somatostatin immunoreactivity. The duodenum was the primary site in 18 of 20 further published cases of carcinoid tumour and neurofibromatosis. Phaeochromocytoma was also present in six of these 27 cases with neurofibromatosis and duodenal carcinoid tumour. Six patients have been reported with Von Hippel-Lindau complex, phaeochromocytoma and islet cell tumour. A further 11 patients showed phaeochromocytoma and islet cell tumour. No cases of Von Hippel-Lindau complex had a carcinoid tumour, and no cases of neurofibromatosis had an islet cell tumour. We conclude that the association of neurofibromatosis, duodenal carcinoid tumour and phaeochromocytoma forms a distinctive neuroendocrine syndrome, sharply separated from the association of Von Hippel-Lindau complex with islet cell tumour and phaeochromocytoma. This separation is important in pathogenesis, diagnosis and clinical management.

Adenoma, Islet Cell↗