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Biomedical subjects

D S Gardiner

Publications and source records attributed to D S Gardiner.

At least 19 recordsLinked to original sources

Histological processing variability in the determination of lateral resection margins in rectal cancer.

BACKGROUND: Involvement of the lateral resection margin (LRM) has been shown to be a reliable predictor of local recurrence of rectal cancer. Accurate determination of the LRM status is crucial in selecting patients for postoperative radiotherapy. However, variability in processing factors may affect the measurement of the LRM. AIM: To investigate how formalin fixation and laboratory processing affects the measurement of the LRM. METHODS: For this study, rectal cancer specimens (n = 9) were fixed in formalin for 4 days and then sectioned transversally, and one half of the specimen was sent for processing. The effacing tumours were placed back in formalin for another 3 days. At day 7, the effacing tumour block (mirror image) was sent for processing. The longest and the shortest perpendicular resection margins for each of the day 4 and day 7 specimens were measured. In a second experiment, control tissue (colon; n = 40), length 10 (0.05) mm, was also processed from a normal sigmoid colon. Specimens were retained in formalin for 24 h (n = 12), 48 h (n = 12), 72 h (n = 9) and 96 h (n = 7). The degree of tissue shrinkage was then recorded. Variations in the recorded LRM and length of colonic tissue are presented as a median (interquartile range) and data were compared using analysis of variance. RESULTS: In the cases of rectal cancer, the variation in measured LRM between day 4 and day 7 specimens was 3.2 (1.5-5) mm. In 30 of the 37 comparisons, the day 7 LRM increased in length, whereas in the remaining 7 it decreased. In the second experiment, control tissue of the original length 10 (0.05) mm increased in length to 10.9 (8.9-13.0) mm, p<0.01. CONCLUSION: These results suggest that the fixation period/laboratory processes result in measurable differences in the reported LRM. This degree of variation has implications for the reliable reporting of the LRM, predicting local recurrence rates and planning subsequent adjuvant radiotherapy.

Formaldehyde↗

Delayed death owing to blunt cardiac injury.

Two cases of blunt myocardial injury to the region of the anterior descending branch of the left coronary artery causing death are described. In one case, direct injury appeared to have resulted in myocardial infarction, whereas in the other, cardiac arrhythmia (possibly secondary to coronary artery spasm) was implicated. Although apparently uncommon, deaths following blunt injury to the coronary arteries may cause death, but are difficult to predict and prevent.

Journal Article↗

Primary mycobacterial infection of the uvula.

Tuberculosis, and non-tuberculous mycobacterial infections are becoming more common thus it is more likely that otolaryngologists will encounter these conditions. We describe an otherwise well patient, with symptoms and signs from chronic uvular inflammation, who proved to have a primary mycobacterial infection. This is an unique presentation in the literature and reminds clinicians of the need, where uncertainty exists in diagnosis, to consider mycobacterial infections.

Adult↗

Overexpression of p53 protein and its significance for recurrent progressive bladder tumours.

OBJECTIVE: To determine the prognostic value of the overexpression of p53 protein as determined by immunohistochemistry in recurrent progressive transitional cell carcinomas of the bladder. PATIENTS AND METHODS: A total of 222 tumours from 86 patients with recurrent disease, 20 from patients with no evidence of recurrence after resection of initial tumour and 11 normal bladder (controls) were investigated. Using a microwave technique to expose antigens, formalin-fixed sections were immunohistochemically stained for p53 using a polyclonal antiserum. Two independent observers scored the sections for evidence of overexpression of p53. RESULTS: Of 86 patients with recurrent disease, 51 demonstrated overexpression of p53 protein, as did six of 20 patients with non-recurrent disease. Overexpression was not linked to recurrence (P = 0.5) but was related to worsening histological stage (P < 0.01) and increasing grade (P < 0.01). Regression analysis showed that overexpression of p53 for the primary tumour was not of predictive prognostic value for death from bladder cancer, time to progression or time to recurrence. Tumour grade was the only variable of prognostic value in all the statistical models. Patients with overexpression of p53 showed no reduction in overall survival. CONCLUSION: These findings suggest that overexpression of p53, as determined immunohistochemically, appears to have no predictive prognostic value over stage and grade in bladder tumours.

Aged↗

C-erbB-2 gene amplification: a molecular marker in recurrent bladder tumors?

C-erbB-2 gene amplification and protein overexpression have been implicated as prognostic markers for patients with recurrent progressive bladder tumors. This event has been investigated as a potential diagnostic indicator in archival samples of transitional cell carcinoma of the bladder. Two hundred thirty-six bladder tumors from 89 patients with recurrent disease (mean follow-up, 4 years), 20 tumors from patients with no evidence of bladder tumor recurrence (mean follow-up, 7 years) and 10 normal bladder controls (patients with no history of transitional cell carcinoma) were studied. A differential PCR was used to provide a semiquantitative estimate of C-erbB-2 gene amplification. Protein overexpression was assessed immunohistochemically. Sixteen of 89 patients with recurrent disease had evidence of C-erbB-2 gene amplification. No C-erbB-2 gene amplification was seen in the nonrecurrent tumors or normal bladder controls. Of the 89 patients with recurrent bladder tumors, 43 had evidence of progressive disease, and of these, 14 patients exhibited C-erbB-2 gene amplification, indicating a strong association with gene amplification and progressive disease (P < 0.0005). Gene amplification in these patients was seen only after disease progression had occurred. Protein overexpression was seen in 50% of patients with recurrent and 45% of patients with nonrecurrent disease. No protein overexpression was seen in normal controls. Protein overexpression could not be linked to disease progression. C-erbB-2 gene amplification and protein overexpression were of predictive value in multivariate analysis for overall bladder cancer death; however stage and grade remained the most important independent prognostic variables. C-erbB-2 gene amplification and protein overexpression were of no value as independent markers for the prediction of disease recurrence or progression. It appears from these results that the role of C-erbB-2 as a diagnostic marker may far outweigh its usefulness as a prognostic indicator.

Aged↗

Long-term outcome of the use of OKT3 to treat steroid-resistant acute renal allograft rejection.

OKT3 was used to treat steroid-resistant acute renal allograft rejection in 30 of 496 adult patients transplanted over a 6-year period. Rejection was reversed (defined as a fall in serum creatinine by 50% or more within 30 days of treatment with OKT3) in 40% of cases. Successful reversal was significantly more likely when rejection occurred shortly after transplantation (t ratio -2.53; P = 0.019). The long-term outcome was disappointing; the actuarial graft survival at 1 year from the start of treatment with OKT3 was 42%, and no grafts have thus far survived longer than 3 years. Graft survival was shorter in older patients (coefficient/standard error 2.226; P < 0.05), and no other predictor of long-term outcome was identified. Patient survival at 3 years was 88%. Serious infection occurred in 33% of patients, with two deaths. Our experience suggests that treatment with OKT3 is unlikely to reverse acute renal allograft rejection in more than half of patients where rejection is resistant to steroids. Although long-term graft survival occurred in a few cases, the overall long-term outcome was disappointing, particularly in older patients. Finally, our analysis indicates the difficulty of predicting which patients will derive long-term benefit when OKT3 is used to treat steroid-resistant rejection.

Acute Disease↗

A comparative study of the glomerular peripolar cell and the renin-secreting cell in twelve mammalian species.

The peripolar cell is a glomerular epithelial cell situated within Bowman's capsule at its vascular pole. It is believed to be a secretory cell which forms part of the juxtaglomerular apparatus. Scanning electron microscopy was used to perform a comparative study of the morphology and number of peripolar cells in twelve mammalian species. The number of renin-secreting cells in kidney sections stained by renin antibodies and immunocytochemistry was counted. There was a marked inter-species variation in the number, size and appearance of peripolar cells. They were largest and most abundant in sheep and goat and fewest in dog, cow and human. There was no correlation between the numbers of peripolar cells and renin-secreting cells. This does not support the view that the peripolar cell is part of the juxtaglomerular apparatus.

Animals↗

Peripolar cells, granulated glomerular epithelial cells, and their relationship to the juxtaglomerular apparatus in malignant hypertension.

We have examined 12 autopsy kidneys from cases of malignant hypertension and compared them with normal controls. Peripolar cells and other granulated glomerular epithelial cells were counted in serial paraffin sections, and renin-containing cells were quantified using an immunoperoxidase technique and a human renin antiserum. There were significantly more peripolar cells and other granulated glomerular epithelial cells in the cases of malignant hypertension. Most granulated glomerular epithelial cells were podocytes, situated at the periphery of the tuft. Peripolar cells correlated in number with other granulated glomerular epithelial cells and they had a similar distribution within the renal cortex, but there was no correlation between either of these cells and the number of renin-containing cells. There was hyperplasia of renin-containing cells in some juxtaglomerular apparatuses (JGAs), although the proportion of renin-positive JGAs was unaltered. These results suggest that peripolar cells and other glomerular epithelial cells react in a similar way in malignant hypertension, but they do not support the hypothesis that peripolar cells are part of the JGA.

Epithelium↗

Non-granulated peripolar cells exist in the rat glomerulus.

The peripolar cell is a unique cell type in the mammalian glomerulus. Peripolar cells are said to be identifiable during light microscopy by their cytoplasmic granules and by their position at the vascular pole; and during scanning electron microscopy by their distinctive surface morphology. We used both techniques to count peripolar cells in 6 normal rat kidneys. Scanning microscopy revealed that 55(+/- 5)% of glomeruli contained at least one peripolar cell whereas light microscopy revealed granulated peripolar cells in only 4(+/- 2)% of glomeruli. Vascular poles which contained peripolar cells previously identified by scanning were then examined by light and by transmission electron microscopy. Serial sections through these peripolar cells demonstrated the absence of cytoplasmic granules. Our observations suggest that the majority of peripolar cells in the rat contain no granules.

Animals↗

The renin-secreting cell and the glomerular peripolar cell in renal artery stenosis and Addison's disease.

The glomerular peripolar cell may be a secretory component of the juxtaglomerular apparatus. To investigate this hypothesis we studied kidneys with the renin-angiotensin system activated by two different stimuli in order to compare the responses of peripolar cells and renin-secreting cells. We examined 10 human kidneys, removed for renal artery stenosis and 11 autopsy cases of Addison's disease with appropriate controls. We counted granulated peripolar cells in serial paraffin-embedded sections and renin-containing cells were quantified using an immunoperoxidase technique with an antiserum to human renin. There was a five-fold increase in the number of renin-containing cells in both renal artery stenosis and in untreated, but not in treated, Addison's disease. Peripolar cells were increased in number in three cases of renal artery stenosis, but were unaltered in both treated and untreated Addison's disease. Therefore, neither a reduction in renal perfusion pressure (renal artery stenosis), nor sodium depletion (Addison's disease) consistently affect peripolar cells in humans. These findings do not support the hypothesis that the peripolar cell is part of the juxtaglomerular apparatus.

Addison Disease↗

The glomerular peripolar cell--an immunohistochemical study.

The peripolar cell is a recently described glomerular epithelial cell which may be a new secretory component of the juxtaglomerular apparatus (JGA). The purposes of this study were to identify immunohistochemical markers specific for peripolar cells and to elucidate the composition of their cytoplasmic granules. We examined tissue from normal human and sheep kidneys with a variety of monoclonal antibodies and antisera. A minority of peripolar cells showed immunoreactivity for vimentin but no other intermediate filament. Neuroendocrine markers were negative. The granules of peripolar cells contain a variety of plasma proteins with the exception of IgM. It is likely that peripolar cells absorb plasma proteins from the glomerular filtrate. The reason for this is uncertain; however, their unique position at the vascular pole of normal kidneys suggests a specialized function.

Animals↗

Peripolar cells and other granulated epithelial cells in renal biopsies.

The peripolar cell is a recently described glomerular epithelial cell which is situated within Bowman's capsule at the vascular pole. It contains cytoplasmic granules which contain plasma proteins, although it may also have a secretory function. The relationship between peripolar cells, other granulated glomerular epithelial cells and tubular epithelial cells is unclear. We have studied 242 biopsies from 19 types of renal disease for peripolar cells, other granulated epithelial cells and granulated tubular epithelial cells. Peripolar cells were most numerous in mesangioproliferative glomerulonephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis and lupus nephropathy. Other granulated glomerular epithelial cells were most prominent in diffuse lupus nephropathy, focal glomerulonephritis, acute vascular transplant rejection, crescentic glomerulonephritis and mesangioproliferative glomerulonephritis. Granulation of the tubular epithelium was most prominent in minimal change nephrotic syndrome and amyloidosis. It is likely that the granules in tubular epithelial cells represent lysosomes containing plasma proteins which have been absorbed from the tubular fluid. However, granulation of glomerular cells may represent a more specific response to glomerular damage. In addition, peripolar cells are prominent in only certain diseases, suggesting a specialized function.

Amyloidosis↗

Crescentic glomerulonephritis: experience of a single unit over a five year period.

Crescentic glomerulonephritis is a well defined pathological lesion occurring in a range of renal and systemic diseases. We have retrospectively reviewed the aetiology, clinical features and outcome in 60 patients presenting over a five and a half year period. Most patients were elderly (median age 61 years, range 16-84 years). The majority presented with severe renal impairment, 32 requiring dialysis at admission. The degree of glomerular crescent formation on biopsy was closely related both to initial dialysis dependence and the ensuing response to immunosuppression. Forty-three patients received immunosuppressive treatment. A beneficial response was seen in 40% of patients requiring dialysis, and in 88% of those with less severe renal impairment. A high early mortality was apparent (30% within three months), exclusively affecting elderly patients (all > 60 years), with advanced renal failure (all dialysis dependent), the majority of whom (15 out of 18) had been immunosuppressed. The results suggest that the benefits of immunosuppression in this group may be outweighed by the complications of treatment.

Adolescent↗

The effect of conversion from cyclosporin to azathioprine on renin-containing cells in renal allograft biopsies.

Renal biopsies were examined from 17 renal transplant recipients before and after conversion from cyclosporin to azathioprine, and in 17 patients who remained on cyclosporin. All patients had stable renal function. We used an immunoperoxidase technique with an antiserum to human renin to identify renin-containing cells. We demonstrated hyperplasia of renin-containing cells in patients treated with cyclosporin. Numbers of renin-containing cells decreased after conversion to azathioprine. We suggest that local activation of the intrarenal renin-angiotensin system could mediate the effects of cyclosporin on renal haemodynamics. This could play a role in the pathogenesis of cyclosporin nephrotoxicity and cyclosporin hypertension.

Azathioprine↗

The glomerular peripolar cell: a review.

There is now morphological evidence from several species that the peripolar cell is a distinctive glomerular cell which may have a secretory function, although a secretory product has not been identified. Peripolar cells, like other glomerular epithelial cells, probably absorb plasma proteins from the glomerular filtrate. Peripolar cells may participate in regulation of sodium balance and the changes in renal function which occur at the time of birth. They are ideally situated to monitor the composition of the glomerular filtrate and/or the calibre of the glomerular arterioles. The relationship between peripolar cells and other granulated glomerular epithelial cells must be clarified, however their morphology and unique anatomical site is suggestive of a specialised function.

Animals↗