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Biomedical subjects

P A Drew

Publications and source records attributed to P A Drew.

At least 19 recordsLinked to original sources
PubMed2004

Aspirin and indomethacin for the prevention of experimental port-site metastases.

BACKGROUND: Nonsteroidal antiinflammatory drugs have been shown to have antitumor and chemopreventative effects. We investigated the potential of these drugs to inhibit port-site and intraperitoneal metastases. METHODS: The antiproliferative effect of aspirin and indomethacin on tumor cells was measured in vitro and in vivo. The in vivo experiments used DA rats to measure the effects of aspirin and indomethacin on the development of port-site metastases and the proliferation of intraperitoneal tumor cells after laparoscopy. RESULTS: In vitro, aspirin and indomethacin had an antiproliferative effect on tumor cells, inhibiting cell division and killing cells in a concentration and time-dependent manner. Orally administered aspirin and indomethacin, at the maximum tolerated dose, did not reduce the rate of intraperitoneal tumor cell division and had no effect on peritoneal metastases, or the number or size of port-site metastases. CONCLUSIONS: Despite promising in vitro studies, this study does not suggest there will be any clinical therapeutic value associated the use of aspirin or indomethacin for the prevention of the spread of tumor following the spillage of cells into the peritoneal cavity at laparoscopic surgery.

Animals↗
PubMed2004

Cyclo-oxygenase-2 expression in esophageal adenocarcinoma as a determinant of clinical outcome following esophagectomy.

The aim of this study was to determine if cyclo-oxygenase-2 (COX-2) expression in adenocarcinoma of the esophagus affects survival outcome in patients undergoing esophagectomy. Ten patients surviving more than 3 years following an esophagectomy for adenocarcinoma of the esophagus were identified from an esophagectomy database maintained by the University of Adelaide Department of Surgery. An additional group of 10 patients, who underwent esophagectomy for adenocarcinoma, but who died within 12 months of surgery due to recurrent disease, were also identified. Pieces of the original formalin fixed carcinoma tissue embedded in paraffin blocks from all of these patients were obtained, and slices of the tumor specimens underwent immunohistochemical staining with COX-2 protein. The extent of staining was then graded by a single 'blinded' pathologist: grade 0, no staining; grade 1 +, limited staining; and grade 2 +, strong staining. Kaplan-Meier survival curves were then constructed and used to determine correlations between survival and COX-2 staining, tumor T-stage, local lymph node metastases, and tumor vascular invasion. Ninety-five percent (19/20) of patients stained positively for COX-2. Patients with grade 2 + staining had a significantly poorer survival outcome compared to grade 1 + patients (P = 0.03). There were also trends towards shorter survival with worsening T-stage, lymph node metastasis and vascular invasion. COX-2 protein appears to be expressed by most esophageal adenocarcinomas. An increased level of expression of COX-2 was associated with a poorer survival outcome in this study. COX-2 protein expression association could be a better prognostic indicator for esophageal adenocarcinoma than traditional histopathological staging.

Adenocarcinoma↗
PubMed1999

Immune cell subpopulations in regenerated splenic tissue in rats.

BACKGROUND: Asplenic patients have an increased risk of infections. Operations such as autotransplantation or splenic artery ligation have been suggested to ensure retention of functional splenic tissue after splenectomy, but their protective value is unclear. Immune responses, such as production of antibody, remain impaired in humans and animals even when such tissue is present, and phagocytosis is less efficient than by normal spleen tissue. In the present study the cellular composition of regenerated tissue is determined. METHODS: Splenic tissue was obtained from rats 6-9 months after splenic autotransplantation, splenic artery ligation or sham operation. The lymphocyte and macrophage subpopulations were labelled using a panel of monoclonal antibodies and analysed by flow cytometry. RESULTS: Both the total number of cells and the number of cells per gram of tissue were significantly reduced. There was a substantial reduction in the percentage of some of the cells examined (CD4+ and CD8+ T lymphocytes subsets), but not all (B lymphocytes, ED1+ and ED2+ macrophages, OX2+ and OX6+ cells). CONCLUSIONS: The reduction in the T lymphocyte subsets in regenerated splenic tissue compared with the normal spleen might explain the immunological dysfunction which persists after splenic autotransplantation. The reduction in the number of macrophages may be responsible for the alteration in phagocytic efficiency of regenerated splenic tissue.

Animals↗
PubMed1998

Fat distribution and changes in the blood brain barrier in a rat model of cerebral arterial fat embolism.

This study was designed to determine the distribution of fat which reaches the brain by the internal carotid artery, and the consequent alterations in the blood brain barrier, in a rat model of cerebral arterial fat embolism. The distribution of the blood flow in this model was determined by the injection of radiolabelled microspheres. Over 44% were trapped in the brain, 43% in the extracerebral tissues of the head and neck, and 7% in the lungs. Over 30% of radiolabelled triolein was present within the brain 30 min after injection, and 4% still remained after 17 days. Approximately 25% of the triolein which went to the brain moved through the cerebral vessels and left within the first 15 min. The majority of the triolein distributed to the ipsilateral cerebral hemisphere, with significantly less to the contralateral cerebral hemisphere, brain stem and cerebellum. The blood brain barrier opened, as measured by uptake of 99mTc, within the first 15 min and remained open for at least 3 days. A significant percentage of fat reaching the brain persists for days, and causes rapid and long-lasting damage to the blood brain barrier.

Animals↗
PubMed1998

Pulmonary cryptococcosis and pituitary Cushing's disease.

Pulmonary cryptococcosis was diagnosed by examining smears obtained by fine-needle aspiration (FNA) in a patient with pituitary Cushing's disease. FNA allowed for rapid diagnosis and prompt treatment of a potentially serious infection. The patient fully recovered from her pulmonary disease. Although opportunistic infections may occur in patients with endogenous Cushing's syndrome, it is rare to see such infections in the subset of patients with pituitary Cushing's disease. Hypercortisolism associated with Cushing's syndrome appears to induce a transitory immune deficiency state and opens a window of opportunity for certain infectious agents such as Cryptococcus neoformans to exploit. To our knowledge, this is the third such case reported in this clinical setting, and the first diagnosed by FNA.

Cryptococcosis↗
PubMed1998

Prostatectomy tissue for research: balancing patient care and discovery.

The application of modern technology in basic research often requires fresh tissue from human organs. The acquisition of this tissue challenges the anatomic pathologist to balance the needs of the basic scientist with the requirements of quality patient care. Our experience indicates that fresh tissue adequate for research can be obtained from neoplastic prostate glands without compromising patient care. The process requires dedicated, knowledgeable individuals and extensive documentation. Potential problems include low yield for research studies, loss of all residual carcinoma, compromise of the specimen margin, and unforeseen costs. Best collaborations occur in situations in which basic scientists and anatomic pathologists establish a working relationship and develop a mutually supportive means of funding.

Antineoplastic Agents, Hormonal↗
PubMed1997

Can androgen deprivation with leuprolide be predicted from histology alone? If not, why not?

PURPOSE: Androgen deprivation therapy with analogues of luteinizing hormone-releasing hormone produces distinctive histological changes in neoplastic and nonneoplastic prostate tissue. Others have described these features in cases in which treatment status was known. To our knowledge the specificity and sensitivity of luteinizing hormone-releasing hormone effects based only on histology and possible reasons for interobserver variation have not been addressed previously. MATERIALS AND METHODS: Slides from 97 prostatectomies performed in a 3-year period were reviewed by 2 observers blinded to knowledge of previous hormonal treatment. The observers evaluated each case, recording the presence or absence of 14 features associated with androgen deprivation therapy, and then made an overall assessment regarding treatment status. RESULTS: Of the 97 patients 31 had received androgen deprivation therapy with the luteinizing hormone-releasing hormone agonist leuprolide. A luteinizing hormone-releasing hormone effect was identified by the 2 observers in 26 and 28, respectively, of the 31 cases (83.9 versus 90.3% sensitivity and 92.4 versus 80.3% specificity). Including focal changes as consistent with androgen deprivation therapy increased sensitivity but decreased specificity. Of the 14 features 12 had a significant association for predicting treatment status. CONCLUSIONS: Interobserver variations in interpretation occurred although both examiners were experienced in the evaluation of luteinizing hormone-releasing hormone effects and they used exactly the same criteria. These variations were apparently due to differences in the value (mental weight) given by each observer to the features assessed in each case. Predicting treatment status was optimized by noting a luteinizing hormone-releasing hormone effect only when changes were diffuse, improving specificity significantly with only a modest decrease in sensitivity.

Adenocarcinoma↗
PubMed1996

The histogenesis of clear cell adenocarcinoma of the lower urinary tract. Case series and review of the literature.

Clear cell adenocarcinoma of the lower urinary tract is a rare neoplasm whose histogenesis has not been thoroughly investigated. We have examined six specimens of clear cell adenocarcinomas collected from three institutions using histological, histochemical, and immunohistochemical techniques. Results indicate that almost all clear cell adenocarcinomas of this region express morphological and antigenic features, suggesting müllerian differentiation, and that müllerian differentiation is not a feature of either nonclear cell adenocarcinomas or normal female paraurethral glands. Including the authors' six specimens, 46 specimens have been reported in the available English literature. The accumulated experience confirms the initial impression that these tumors develop predominantly in the urethras of women and occur over a wide age range. Despite high stage at diagnosis, most patients have been alive with no evidence of disease when reported, a prognosis that seems to apply regardless of length of follow-up.

Acid Phosphatase↗
PubMed1996

Prognostic factors in carcinoma of the vulva: a clinicopathologic and DNA flow cytometric study.

The clinical staging of carcinoma of the vulva is a predictor of patient survival; however, the significance of other prognostic factors remains somewhat controversial. Length of survival after diagnosis of invasive squamous cell carcinoma was determined for 39 clinically staged and surgically treated patients who were followed at our institution. Clinical stage, tumor type, use of radiotherapy (RT), histopathologic features (invasive pattern, depth of invasion, lymph node status, nuclear grade, adjacent dysplasia, desmoplasia, inflammation) and DNA ploidy (determined by flow cytometry from paraffin-embedded tissue) were evaluated as predictors of survival. Kaplan-Meier survival curves were generated for strata defined by each of the various predictors and compared using the log-rank test. Advanced stage (p = 0.0002), RT use (p = 0.0004), "spray" invasive pattern (p = 0.005), positive lymph node status (p = 0.001), increased positive lymph node number (p = 0.016), and greater depth of invasion (p = 0.039) were associated univariantly with decreased survival time. Spray invasive pattern (p = 0.018), positive lymph node status (p = 0.030), positive lymph node number (p = 0.040), and RT use (p = 0.045) continued to be associated with decreased survival time after controlling for stage. Of the significant factors, invasive pattern stands out as a qualitative feature that may have potential benefit in predicting survival independent of clinical stage in patients with vulvar carcinoma.

Adult↗
PubMed1996

The nested variant of transitional cell carcinoma: an aggressive neoplasm with innocuous histology.

The nested variant of transitional cell carcinoma (TCC-NV) is a rare neoplasm; only eight cases have been described. This report reviews the clinicopathologic features of 16 additional examples. The cases were collected from consultations received during a 13-year period. In most instances, a consultation was sought because the histologic features suggested an atypical proliferation of Brunn's nests or a lesion similar to the previously published examples of TCC-NV. Clinical data were gathered and tissues were studied to exclude prostatic cancer and adenocarcinoma. TCC-NV is characterized by the presence of irregular nests and/or tubules of transitional cells infiltrating the lamina propria without surface involvement. Neoplastic cells tend to have innocuous features but at least a few cells in every case are cytologically anaplastic. There is a marked male predominance. Synchronous or metachronous TCCs of more usual histologic make-up may occur. After a follow-up averaging 16.6 months, only three patients are known to be alive with no evidence of disease. Clinicopathologic information from our 16 cases combined with the 8 previously reported examples confirms that TCC-NV is a persistent and aggressive neoplasm notable for its innocuous appearance in histologic preparations.

Acid Phosphatase↗
PubMed1995

Pathology of androgen deprivation therapy in prostate carcinoma. A comparative study of 173 patients.

BACKGROUND: Leuprolide, an agonist of luteinizing hormone-releasing hormone (LH-RH), and flutamide, an antiandrogen, increasingly are being used in the treatment of clinically localized prostate cancer. Only two small series (of 23 and 12 patients) have been published on the distinctive pathologic changes induced in the prostate by androgen deprivation therapy with discrepancies on the presence of squamous metaplasia, necrosis, and possible tumor destruction by combined androgen deprivation therapy. METHODS: One hundred and thirteen radical prostatectomy specimens obtained after at least 3 months of leuprolide-flutamide androgen inhibition therapy and 60 nonhormonally treated prostates in randomly selected clinical Stage T2 prostate adenocarcinoma patients were entirely sectioned. Distinctive histologic findings were tabulated and their statistical value determined. RESULTS: Resection margins of excision were involved by tumor in 43% of untreated and in 19% of androgen-deprived patients. Characteristic changes in androgen-inhibited nontumor glands included atrophy, basal cell prominence, vacuolated luminal cell layer, and squamous and transitional cell metaplasia. Prostatic intraepithelial neoplasia (PIN) was observed in 35% of treated patients. The presence of small tumor glands separated by stroma was the most frequently noted effect of androgen deprivation on prostate adenocarcinoma; pyknosis and branching empty spaces were less frequent. Large clear tumor cells within an inflammatory response was a third histologic pattern. Apparently unaltered tumor areas were observed in 43% of prostates exposed to androgen deprivation therapy. CONCLUSIONS: Androgen deprivation therapy results in histologically distinctive changes that can be recognized in both nonneoplastic and neoplastic prostate tissue. Residual tumor was present in all 113 treated radical prostatectomy specimens. In addition to glandular shrinkage, therapy was associated with statistically significant reductions in the frequency of high grade PIN and extension of cancer to prostate specimen margins of excisions.

Androgen Antagonists↗
PubMed1995

Cerebral arterial fat embolism in the rabbit.

This study was designed to measure the effects of cerebral arterial fat embolism on cerebral blood flow and function. Rabbits were injected via the left internal carotid artery with the neutral triglyceride triolein. Left cerebral blood flow was measured by laser Doppler flowmetry, and left sided brain function by electrocorticogram and cortical somatosensory evoked responses following electrical stimulation of the forepaw. Readings were taken for 2 h before injection to establish a baseline, and for 3 h after injection. Cerebral blood flow was significantly decreased at 45 min after the injection of the lipid, then progressively decreased further to approximately 50% of baseline after 2 h, at which level it remained for the last hour of the experiment. The electrocorticogram was rapidly, but transiently, suppressed. The evoked responses did not differ from baseline at each of the time points measured. Using 125I-triolein, 2.49% of the injected dose was measured in the brain 3 min after injection. The results show that in this rabbit model of cerebral arterial fat embolism only a small percentage of injected lipid passes into the brain, but this is sufficient to cause a reduction in cerebral blood flow over the following 2 h. The evoked responses never alter significantly from baseline values.

Animals↗
PubMed1994

IgG-mediated phagocytosis in regenerated splenic tissue.

The risk of severe infections after splenectomy is well established. Operations such as auto-transplantation, splenic artery ligation or partial resection have been advocated for the retention or regeneration of splenic tissue following splenic trauma. The potential of such tissue to protect from infection is unclear. The ability of splenic tissue to phagocytose IgG opsonized syngeneic erythrocytes was measured in rats 6 months following splenectomy and splenic autotransplantation, splenic artery ligation, total or partial splenectomy, and compared with eusplenic controls. In eusplenic and partially splenectomized rats 71% of the label was cleared at 3 h, compared with approximately 50% in rats following total splenectomy, splenectomy and splenic autotransplantation or splenic artery ligation. The autotransplanted and the ligated splenic tissue cleared less than 10% compared with control spleen, but there was no difference between them when clearance was expressed as uptake per gram of tissue. Splenic autotransplants and ligated spleens were small and histologically abnormal, with an increase in the red pulp, significantly less white pulp and marginal zone, and the frequent absence of a central arteriole in the white pulp. The clearance of label was proportional to the amount of red pulp in the tissue, although the red pulp from the regenerated tissues was not as efficient at phagocytosis as control red pulp. The tissue which regenerated following autotransplantation or splenic artery ligation did not result in greater clearance of erythrocytes from the circulation than that which occurred in splenectomized rats.

Animals↗
PubMed1992

Antibody responses following splenectomy: implications for the timing of prophylactic vaccination.

Antibody responses are reduced both in the short- and long-term after splenectomy. It is not known if this reduction is more profound in the immediate postoperative period compared to later, and consequently, whether there would be an advantage in delaying prophylactic vaccination to ensure a greater antibody response. To investigate this, the effect of splenectomy on the primary and secondary antibody response to sheep red blood cells (SRBC) injected into the peritoneum (IP) of adult male Porton rats was measured after either splenectomy (Spx), sham splenectomy (Sham), anaesthesia only (Ans) or no procedure at all (Con). There was no difference in the titres of antibody between the Con and the Ans rats. There was no difference in the titres of antibody between the Sham and Spx rats, but both had significantly lower titres than the Con rats. In a separate experiment, rats were immunized 1 month or 1 year after splenectomy or sham-splenectomy. One month after the operation the antibody response of the Sham rats had increased and did not differ from that of Con rats, but in rats which had been splenectomized there was a long-term suppression of the antibody response, which did not improve for at least one year. The results suggest that, in patients requiring splenectomy for trauma and not able to be vaccinated before operation, there may be no advantage in delaying prophylactic vaccination postoperatively.

Animals↗
PubMed1989

Regeneration and phagocytic function of devascularized spleens.

The phagocytic function of normal splenic tissue and of regenerated tissue following splenic artery ligation was investigated in rats using radiolabelled stannous fluoride colloid. Colloidal carbon was used to determine the histological location of phagocytosis within the spleen. Six months after ligation, the median weight of the devascularized spleens was 25% of that of spleens in control rats. Technetium stannous colloid clearance by devascularized spleens was reduced to 10% of normal and 25% when corrected for spleen weight. The colloidal carbon injected intravenously was observed primarily in the marginal zone in both normal and devascularized spleens. Histologically, devascularized spleens contained significantly less white pulp and marginal zone. The splenic tissue which regenerates following ligation does not have the phagocytic ability of normal splenic tissue. This may be due to the decreased regrowth of the lymphoid compartments of the spleen.

Animals↗
PubMed1989

Scanning electron microscopy of dysplastic Barrett's epithelium.

Twenty-six patients with Barrett's esophagus (BE) were followed prospectively by endoscopic examination and biopsy. Two biopsies were taken from each of 4 areas of BE. One was processed for light microscopy (LM) and one for scanning electron microscopy (SEM). Those in whom dysplastic BE was demonstrated by LM were reexamined at 6-mo intervals, and the others at yearly intervals. One patient had low grade dysplasia (LGD) by LM on entry, and in 2 others, LGD was recognized on the second examination. These changes have persisted in semiannual examinations over 3, 2, and 2 yr, respectively. SEM prints were examined without knowledge of LM findings, and features that might correlate with LGD by LM were sought. SEM findings were similar to those of Zwas et al. (Gastroenterology 90:1932, 1986) in that most glandular cells had surface features unlike either gastric or intestinal cells but unique to BE. In the patient with LGD on entry, there was an aggregate of very large cells covered by short microvilli with bald patches. In the other patients with LGD, there was more variation in size and shape of cells than in nondysplastic cases.

Adult↗