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Biomedical subjects

R A Cahill

Publications and source records attributed to R A Cahill.

At least 19 recordsLinked to original sources
PubMed2006

Rapid assessment breast clinics--evolution through audit.

This observational, cohort study aimed to examine the potential utility of Rapid Assessment Breast Clinics (RABC) beyond cancer detection at presentation. One thousand four hundred and twenty nine women were studied over an 18 month period. 154 (10.7%) had breast cancer - 87.7% of whom were seen expediently with 92.9% being diagnosed at one attendance. One hundred and forty three (10%) of those with a benign diagnosis were found by routine questioning to have significant familial risk separate to their reason for referral. Despite careful triage, considerable contamination of appointment allotment occurred with many who were correctly triaged as non-urgent being seen 'urgently'. One hundred and seventy six attendees (12.3%) had neither the symptom that triggered referral, nor breast lump, nipple discharge nor family history of breast cancer, while 283 (19.8%) had no objective clinical or radiological abnormality. Although RABC reliably categorise malignant versus non-malignant diagnoses despite cluttering by low risk women, a significant proportion of non-cancer patients still require address of future risk rather than reassurance of their present status alone.

Adult↗
PubMed2006

The effect of perioperative beta-blockade on the pulmonary function of patients undergoing major arterial surgery.

INTRODUCTION: Concern about the potential detrimental side-effects of beta-blockade on pulmonary function often dissuades against their perioperative use in patients undergoing major arterial surgery (especially in those with chronic obstructive pulmonary disease (COPD)). In this study we aimed to establish prospectively the clinical relevance of these concerns. METHODS: After ethics committee approval and individual informed consent, the pulmonary function of twenty patients (mean age 68.7 years (range 43-82), 11 males) scheduled to undergo non-emergency major vascular surgery was studied by recording symptoms and spirometry before and after institution of effective beta-blockade. Fifteen patients (75%) had significant smoking histories (mean pack years/patient=50), while 12 (60%) had COPD. RESULTS: All patients tolerated effective beta-blockade satisfactorily without developing either subjective deterioration in symptoms or significant change on spirometry. The mean change in FEV1 following adequate beta-blockade was 0.05+/-0.24 liters (95% CI -0.06 to +1.61), p=0.35, giving a mean percentage change of 3.18%+/-11.66 (95% CI -2.26 to 8.62). CONCLUSIONS: Previously held concerns about worsening pulmonary function through the short-term use of beta-blockers should not dissuade their perioperative usage in patients with peripheral vascular disease. Furthermore, the accuracy of pulmonary function tests in preoperative assessment and risk stratification also appears unaffected by this therapy.

Adrenergic beta-Antagonists↗
PubMed2006

Concomitant detection of systemic atherosclerotic disease while screening for abdominal aortic aneurysm.

INTRODUCTION: Although population screening for abdominal aortic aneurysm (AAA) has/had a significant impact on disease-specific mortality, coexisting systemic atherosclerosis represents the major impediment to improved longevity. We examined the feasibility and yield of full cardiovascular assessment concomitant with screening for AAA detection. METHODS: A total of 1032 asymptomatic men over the age of 50 years (328 were >60 years) underwent a detailed cardiac health questionnaire, sphygmomanometry, body mass index calculation, fasting lipid profiling, ultrasonographic (US) examination of their infrarenal aorta and carotid arteries, and treadmill exercise stress testing. Framingham and SCORE project estimations of the 10-year risk of ischemic heart disease (IHD) and fatal cardiovascular disease (CVD) of any cause were calculated for the men with an AAA and in those>60 years but with neither AAA nor known cardiac disease. RESULTS: Overall, we detected an AAA>3 cm in 30 men (2.9%). Unaddressed obesity, smoking, hypertension, impaired glucose metabolism, and hypercholesterolemia were commonly identified in individuals both with and without an AAA, being notably frequent in those>60 years without an AAA. The 10-year risk of IHD and CHD in those>60 years was similar regardless of whether an AAA was present. Doppler screening for significant carotid stenosis had detection rates similar to those for aortic US scanning, being most useful in those>65 years of age. Exercise stress testing, however, was of only limited value when used nonselectively. CONCLUSIONS: Modifiable atherosclerotic disease and cardiovascular risk can be readily detected in individuals presenting for AAA screening and are present to a significant degree at an earlier age. Consideration of selected, additional investigations is required to maximize the value of generalized screening programs.

Aged↗
PubMed2005

Activated protein C attenuates acute ischaemia reperfusion injury in skeletal muscle.

Activated protein C (APC) is an endogenous anti-coagulant with anti-inflammatory properties. The purpose of the present study was to evaluate the effects of activated protein C in the setting of skeletal muscle ischaemia reperfusion injury (IRI). IRI was induced in rats by applying rubber bands above the levels of the greater trochanters bilaterally for a period of 2h followed by 12h reperfusion. Treatment groups received either equal volumes of normal saline or activated protein C prior to tourniquet release. Following 12h reperfusion, muscle function was assessed electrophysiologically by electrical field stimulation. The animals were then sacrificed and skeletal muscle harvested for evaluation. Activated protein C significantly attenuated skeletal muscle reperfusion injury as shown by reduced myeloperoxidase content, wet to dry ratio and electrical properties of skeletal muscle. Further in vitro work was carried out on neutrophils isolated from healthy volunteers to determine the direct effect of APC on neutrophil function. The effects of APC on TNF-alpha stimulated neutrophils were examined by measuring CD18 expression as well as reactive oxygen species generation. The in vitro work demonstrated a reduction in CD18 expression and reactive oxygen species generation. We conclude that activated protein C may have a protective role in the setting of skeletal muscle ischaemia reperfusion injury and that this is in part mediated by a direct inhibitory effect on neutrophil activation.

Acute Disease↗
PubMed2005

Malignant fibrous histiocytoma masquerading as a pseudoaneurysm of the profunda femoris.

We describe a patient with an aggressive soft tissue sarcoma masquerading as a profunda femoris pseudoaneurysm. A 73-year-old patient presented with a pulsatile swelling in her right groin. Femoral angiography demonstrated what appeared to be a pseudoaneurysm of the right profunda femoris artery and she underwent an open surgical repair. The patient represented 2 months later with an enlarging non-pulsatile, non-tender mass at the site of the wound. Open biopsy determined the diagnosis as malignant fibrous histiocytoma (MFH). An en bloc resection of the mass with reconstruction of the femoral artery and vein using PTFE grafts was performed.

Aged↗
PubMed2005

The impact of bone marrow micrometastases on metastatic disease-free survival in patients with colorectal carcinoma.

AIMS: The biological relevance of bone marrow micrometastases (BMM) in colorectal cancer remains unknown. Here, we investigate their nature by examining the impact of the presence of BMM on metastatic disease-free survival in a cohort of patients with this disease. METHODS: Sixty-three consecutive patients undergoing surgery for colorectal cancer of any stage were studied after approval of the study protocol by the local ethics committee and with full individual informed consent. All had bilateral iliac crest bone marrow aspirates prior to operation. Aspirates were then examined for the presence of aberrant cytokeratin-18-positive cells by a blinded observer using both flow cytometric and APAAP immunohistochemical techniques. RESULTS: Mean follow-up after surgery was 4.6 years (range 1.9-6.9) for those without hepatic metastases at diagnosis. Seven of 34 patients with Dukes' stage A or B developed metastatic disease after a mean interval of 4.7 years (range 3.8-6.8). However, only 2 of these patients demonstrated BMM at the time of surgery. Nine of 15 patients with Dukes' C carcinoma at the time of surgery subsequently developed metastases after a mean interval of 4.4 years (range 1.9-6.9). Again, only two of these patients had BMM detectable initially. In only three of the 14 patients known to have metastases at the time of operation (i.e. Dukes''D' disease) were BMM found. CONCLUSION: The presence of BMM as detected by this methodology was not predictive of tumour recurrence or metastasis. This study does not support the consideration of adjuvant therapy based on the presence of BMM at a single pre-operative time point in patients with colorectal cancer.

Adult↗
PubMed2004

Effects of a selective cyclo-oxygenase 2 inhibitor on colonic anastomotic and skin wound integrity.

BACKGROUND: Selective inhibitors of inducible cyclo-oxygenase (COX-2) are of potential benefit in the perioperative period for both their analgesic and, perhaps, antineoplastic actions. However, their effects on laparotomy and intestinal wound healing are unknown. METHODS: Forty adult Sprague-Dawley rats underwent laparotomy, descending colonic transection and handsewn reanastomosis. The animals were randomized to receive either a selective COX-2 inhibitor (rofecoxib, 10 mg/kg) or an equal volume of water by gavage before operation and then daily after surgery. Animals were killed after 3 or 7 days, and their wounds were evaluated by means of tensiometry (skin and colonic wounds) and bursting pressure measurement (colonic anastomoses). In addition, haematoxylin and eosin-stained intestinal sections were examined and scored by a blinded independent observer. RESULTS: Five animals that received rofecoxib had anastomotic leaks by day 7 compared with none in the control group (P = 0.048). Intact colonic suture lines were also significantly weaker in this group (tensile strength at day 3, P = 0.043; bursting pressure on days 3 and 7, both P = 0.019). Skin wound strengths were similar in the two groups at both time points. CONCLUSION: Although beneficial in the treatment of pathological inflammation, selective COX-2 inhibitors may adversely affect colonic anastomotic healing.

Anastomosis, Surgical↗
PubMed2004

Cyclooxygenase-2 expression in primary human colorectal cancers and bone marrow micrometastases.

BACKGROUND: Both the expressions of the inducible form of cyclooxygenase-2 and the presence of bone marrow micrometastases are poor prognostic markers in patients with colorectal carcinoma. AIMS: As cyclooxygenase-2 expression in these tumours is associated with increased metastatic potential in vitro, our objectives were to determine the relationship between cyclooxygenase-2 and haematogenous spread to bone marrow. PATIENTS AND METHODS: Thirty-two patients with resection of colorectal carcinoma were evaluated (median age: 69.5 years). Bone marrow was obtained from all patients from both iliac crests before manipulation of the primary tumour. The tumours were of varying stages at diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical technique. Extent of staining was graded depending on the percentage of epithelial cells staining positive for cyclooxygenase-2. Micrometastases were detected by staining contaminant cytokeratin-18 positive cells in the bone marrow aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry) methods. Fisher's exact probability test was used to calculate statistical significance. RESULTS: Cyclooxygenase-2 expression in the primary tumour was detected in 72% of the patients. Twelve (38%) patients had bone marrow micrometastases detected by either immunohistochemistry or flow cytometry. Of the 12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20 (45%) patients in whom micrometastases were not detected expressed increased levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there was no further association between cyclooxygenase-2 expression and bone marrow micrometastases (P = 0.179 and 1.0). CONCLUSION: In this pilot study, there was no association between cyclooxygenase-2 expression and bone marrow micrometastases in patients with otherwise localised or disseminated disease.

Aged↗
PubMed2004

Nonmyeloablative allogeneic bone marrow transplantation for treatment of childhood overlap syndrome and small vessel vasculitis.

A 13-year-old Caucasian female with a systemic connective tissue disease (overlap syndrome with pulmonary vasculitis) underwent nonmyeloablative allogeneic BMT after failure of prolonged combination immunosuppressives to induce remission. The procedure also included cotransplantation of donor bone chips as a source of stromal cells. The unique protocol allowed good engraftment of hematopoietic (>95%) and bone core stromal cells (>60%). The patient was clinically improved, stable, and off all immunosuppressive medications 36 months post-transplant. To our knowledge, this is the first pediatric nonmyeloablative BMT with cotransplantation of stromal cells solely for treatment of an autoimmune disease.

Adolescent↗
PubMed2004

Radiation-induced femoral arteritis.

Radiation arteritis is currently an uncommon sequalae of external beam radiation, however because of the increasing use of radiotherapy in the management of neoplastic conditions its recognition is increasingly important. We present two cases of debilitating femoral occlusive disease, secondary to radiation exposure, at a long period post irradiation and review the pathophysiolgy and management options for this condition.

Adult↗
PubMed2001

Synchronous high-risk melanoma and lymphoid neoplasia.

Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

Aged↗
PubMed1998

Effect of human pregnancy-specific beta1-glycoprotein on blood cell regeneration after bone marrow transplantation.

Pregnancy-specific beta1-glycoprotein (PSG) is composed of a family of highly homologous proteins initially isolated from human placenta and pregnancy serum. Recent studies showed that PSGs are also present in a number of ectopic sites, including uncultured peripheral blood and bone marrow cells. This report aims at studying the in vivo effect of the PSGs on murine hematopoiesis. The profile of recovery of blood cells after transplantation of viable nucleated bone marrow cells in gamma-irradiated mice with and without the administration of the purified human protein was studied. Five groups of mice were given 0.1 microg human serum albumin, 0.1 microg IL6, 1 microg PSG, 10 microg PSG, and 50 microg PSG, respectively, per mouse per day consecutively for 20 days. The mice were bled once every 2 days, and the platelet and WBC counts were determined using a Nebauer hemacytometer (Hausser Scientific, Buffalo, NY). The recovery of platelet count after bone marrow transplant was much faster in mice receiving 1 microg PSG/day than in animals in any other group. On Day 20 post-transplant, the platelet count of animals in this group reached 178,600 +/- 15,759/microl (mean +/- standard deviation) which was significantly (P < 0.05) higher than that of any other group. On Day 26, the platelet count reached a low normal value of 190,844 +/- 6,380/microl with a range of 185,420-200,500/microl. This value was 3-fold higher than that of the control group (68,600 +/- 15,486/microl in the human serum albumin group). Mice given 1 microg or 10 microg PSG/day also had their WBC count recover significantly faster and achieved a normal value (12,440 +/- 3,680/microl for the 1-microg PSG group, and 12,154 +/- 3,016/microl for the 10-microg PSG group) within the experimental period. On the other hand, the controls, or mice given 50 microg PSG/day did not recover as rapidly and did not achieve a normal WBC count within the experimental period. These results suggest that human placental PSGs enhance platelet and WBC recovery after bone marrow transplant.

Animals↗
PubMed1996

Marrow engraftment and clinical manifestations of capillary leak syndrome.

A capillary leak syndrome occurs frequently in bone marrow transplant patients in addition to graft-versus-host-disease and infection. The underlying pathology is poorly understood but the clinical manifestations of excessive weight gain, ascites, and edema associated with kidney and liver abnormalities suggest a common injury to multiple organs. The clinical courses of 55 allogeneic and autologous marrow transplant recipients were retrospectively reviewed with regard to the presentation of a capillary leak syndrome (CLS). Twenty-nine patients (53%) developed non-cardiogenic pulmonary edema with or without concurrent pleural effusions; the incidence was comparable in allogeneic and autologous recipients. Pulmonary features were accompanied by hepatic dysfunction in 28, renal dysfunction in 22, and central nervous system abnormalities in 17. There was a strong correlation between time of engraftment and the first manifestations of CLS, both of which occurred earlier in allogeneic than in autologous transplant recipients. These data confirm that CLS occurs in both allogeneic and autologous transplant recipients and suggest a pivotal contribution by circulating leukocytes.

Bone Marrow Transplantation↗
PubMed1993

Expression of pregnancy-specific beta 1-glycoprotein genes in hematopoietic cells.

The presence of PSG in blood cells has been demonstrated by immunohistochemical staining. However, the origin of those proteins is not known. This report examines the expression of the PSG genes in different types of freshly isolated blood cells. RNA isolated from bone marrow and peripheral blood cells of healthy individuals was analyzed for PSG transcripts by reverse transcriptase-polymerase chain reaction using synthetic oligonucleotide primers specific for the PSG genes. The level of expression of the PSG genes in different types of cells exhibited significant individual variation. Trace amounts of PSG transcripts could be detected in polymorphonuclear cells (PMN), monocytes and B lymphocytes while T lymphocytes always contained the highest level of transcript. The expression of PSG genes in the blood cells apparently was not affected by the method of isolation nor by overnight culturing of these cells except in the case when lymphocytes were separated by rosetting with sheep red blood cells. All reported PSG transcripts were detected in blood cells. Both type I and type II transcripts of the PSG genes were detected in blood cells with the exception of type II transcript of PSG5 and PSG11 which were only found in the placenta. Tissue specificity in the expression or alternative splicing of some of the PSG family members was implicated.

Alternative Splicing↗
PubMed1991

Hematopoietic reconstitution and prevention of graft-versus-host disease with UVB-irradiated haploidentical murine spleen and marrow cells.

We investigated in a murine model whether UVB irradiation of lymphohemopoietic cells would prevent the development of graft-versus-host disease (GVHD). Preliminary experiments showed that spleen colony (CFU-S) formation by hemopoietic cells was preserved at UVB doses that eliminated lymphocyte proliferation. In a parent into F1 model, UVB irradiation (5 to 15 mJ/cm2) of spleen cells added to normal marrow cells prevented the development of GVHD, whereas all recipients given untreated spleen cells developed GVHD. Syngeneic recipients of marrow exposed to 2.5 to 10 mJ/cm2 of UVB achieved normal hemopoietic reconstitution. Based on these observations, B6D2 F1 (H-2b x H-2d) recipients were given 1,000 cGy of total body irradiation (TBI) followed by transplantation of 5 x 10(6) parental B6 (H-2b) bone marrow cells and 10 x 10(6) B6 spleen cells, either unirradiated or exposed to UVB before infusion. All mice transplanted with cells exposed to 10 or 12.5 mJ/cm2 of UVB survived without GVHD. At 2.5 and 5.0 mJ/cm2, mice showed signs of GVHD, beginning at day 30, and 100% and 80%, respectively, eventually developed chronic GVHD. At 7.5 mJ/cm2, mice had weight loss, from which 60% recovered and survived without GVHD, while 40% died with GVHD. At 15 mJ/cm2, some recipients died from graft failure, while some survived without GVHD. All surviving mice were complete donor-type chimeras. Spleen size and cellularity and in vitro lymphocyte responses correlated inversely with the development of GVHD. Mice without GVHD showed specific tolerance to skin grafts from the second parent strain, while animals with GVHD rejected their skin grafts. Thus, in a murine model UVB irradiation of transplanted hemopoietic stem cells allows for hemopoietic reconstitution and prevents GVHD.

Animals↗