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Biomedical subjects

K Horgan

Publications and source records attributed to K Horgan.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stressful life events and difficulties and onset of breast cancer: case-control study.

OBJECTIVE: To determine the relation between stressful life events and difficulties and the onset of breast cancer. DESIGN: Case-control study. SETTING: 3 NHS breast clinics serving west Leeds. PARTICIPANTS: 399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents. MAIN OUTCOME MEASURES: Odds ratios of the risk of developing breast cancer after experiencing one or more severe life events, severe difficulties, severe 2 year non-personal health difficulties, or severe 2 year personal health difficulties in the 5 years before clinical presentation. RESULTS: 332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1. 81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump. CONCLUSION: These findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.

Adult↗
PubMed1999

Metastatic melanoma of the tonsil.

Metastasis to the tonsils from malignant melanoma is rare. This paper describes one such case in a woman with synchronous breast adenocarcinoma and cutaneous malignant melanoma who had a most unusual clinical course.

Aged↗
PubMed1999

Follow-up of patients with a thin melanoma.

BACKGROUND: The aim of this study was to determine the value of follow-up in two subgroups of patients with a thin melanoma less than 0.76 mm and 0.76-1.5 mm thick. METHODS: The study group comprised all patients presenting to the Cardiff Melanoma Clinic from its introduction in 1976 to the end of 1994. All patients attend follow-up according to a strict protocol, determined by the thickness of the original melanoma (less than 0.76 mm, annually; more than 0.76 mm, every 2 months for 2 years, 3 monthly for 2 years, 4 monthly for 1 year and then annually). RESULTS: In total there were 306 patients with a thin melanoma: 178 with a melanoma thinner than 0.76 mm (group 1) and 128 with a melanoma of 0.76-1.5 mm (group 2). The groups were well matched for age (mean 50.6 (range 8-87) versus 50.6 (range 19-89) years respectively) and length of follow-up (mean 88.6 (range 4-296) versus 80.4 (range 2-296) months). Four patients (2.2 per cent) developed recurrence in group 1 and 16 (12.5 per cent) in group 2. The mean time to recurrence was 84.5 (range 49-143) months in group 1 and 45.3 (range 2-74) months in group 2. All patients in group 1 and 14 of 16 in group 2 died from recurrent disease. CONCLUSION: Follow-up of patients with a melanoma less than 0.76 mm thick is not worthwhile. All recurrences would have been detected by annual review for 7 years in patients with melanomas between 0.76 and 1.5 mm thick.

Adolescent↗
PubMed1998

Intestinal lymphangiectasia, a disease characterized by selective loss of naive CD45RA+ lymphocytes into the gastrointestinal tract.

Intestinal lymphangiectasia (InL) is a disease characterized by hypoproteinemia and lymphocytopenia resulting from blocked intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract. This leads to immunologic abnormalities including hypogammaglobulinemia, skin anergy and impaired allograft rejection. In the present study, we evaluated whether the above immunologic abnormalities are secondary to a quantitative or qualitative disorder of T cells. In initial studies we demonstrated that adult InL patients' peripheral blood contain strikingly (and significantly) reduced numbers of CD4+/CD45RA+ T cells, whereas the numbers of CD4+/CD45RO+ T cells were only moderately (and not significantly) reduced. In addition, the CD4+/CD45RO+ T cell population contained an increased percentage of highly differentiated and previously sensitized cells, as demonstrated by decreased CD27 and CD31 expression and increased HLA-DR and CD69 expression. In subsequent functional studies, we showed that the InL CD4+/CD45RO+ T cells, when stimulated in vitro, proliferate fivefold less than control CD4+/CD45RO+ T cells and produce fourfold more IL-4 and threefold less IFN-gamma and IL-2. Thus, this cytokine production profile also reflects the highly differentiated nature of the residual cell population. Overall, these studies provide new information on the trafficking of naive/mature and Th1/Th2 T cell populations in this disease model.

Adult↗
PubMed1998

PRFLL--a Pinus radiata homologue of FLORICAULA and LEAFY is expressed in buds containing vegetative shoot and undifferentiated male cone primordia.

In angiosperms, the formation of the flower meristem is controlled by partially redundant flower meristem identity genes of which FLORICAULA (FLO)/LEAFY (LFY) plays a central role. It is not known whether formation of reproductive organs of pre-angiosperm species is similarly regulated. Recently, a FLO/LFY-like cDNA, NEEDLY (NLY), has been cloned in a conifer species Pinus radiata (D. Don). Here we report cloning of a different Pinus radiata FLO/LFY-like cDNA, PRFLL. PRFLL had two large regions of high similarity to angiosperm FLO/LFY orthologues: amino acids 61-126 and 247-406 (50% and 81% identity, and 75% and 88% similarity, respectively, to LFY) and shorter regions of local similarity. Overall identity was 53% to LFY and 61% to NLY. Phylogenetic analysis of deduced protein sequences including partial LFY-like sequences from Pseudotsuga menziesii indicated that conifer proteins constituted a separate clade that could be divided into two groups represented by NLY and PRFLL. In contrast to angiosperms, both conifers had two paralogous proteins resembling LFY. Northern hybridisation analysis revealed expression of PRFLL in vegetative buds of juvenile, adolescent and mature trees. The transcript was not detected in vascular cambium, roots or secondary needles. To follow PRFLL expression during the early stages of cone development we analysed a temporal series of buds containing cone primordia, and developing cones, using Northern hybridisation and confocal microscopy in parallel. PRFLL mRNA was detected in buds from dominant and subordinate branches, in which cone and shoot primordia develop, and in developing male cones but not in developing female cones. Expression was particularly high in buds containing axillary primordia prior to their differentiation as male cone primordia. This is consistent with PRFLL being involved in determination of the male cone primordium identity.

Amino Acid Sequence↗
PubMed1998

Immunosuppressive drugs in the treatment of inflammatory bowel disease.

Immunosuppressive (IS) drugs are an important option in the management of both forms of inflammatory bowel disease (IBD): Crohn's disease and ulcerative colitis. As the experience of using these agents in the treatment of IBD has increased and more data have become available on their efficacy, these drugs are being used more extensively. The principle drugs used in clinical practice at this time include: azathioprine (AZA) and its metabolite 6-mercaptopurine (6-MP), methotrexate, and cyclosporin A. AZA and 6-MP are generally considered the first line immunosuppressive agents. These drugs are effective and generally well tolerated by the majority of patients started on them, enabling many patients to avoid the predictable side effects of steroid therapy. Because of their extensive use, it is important that clinicians involved in the care of IBD patients are familiar with the IS drugs used to treat IBD, especially AZA and 6-MP.

Adult↗
PubMed1997

The cystic fibrosis delta F508 gene mutation and cancer.

Following the observation that relatives of cystic fibrosis (CF) patients have an increased mortality due to leukaemia, a study was initiated to determine whether leukaemia patients had an increased prevalence of the delta F508 CF mutation. No increase in carriers were found among leukaemias; however the carrier frequency of the delta F508 mutation appeared to be reduced in patients with malignant melanoma analysed as a control group compared to the normal population. This paper extends our previous study and investigates several other common human tumours, including those of the colon, breast, and lymphoma tissue. Fewer than expected carriers remained among the melanoma group from South Wales. There were fewer than expected carriers among patients with colon cancer compared to the normal population. The prevalence of the delta F508 mutation was normal in lymphomas and leukaemias.

Alleles↗
PubMed1997

A randomized controlled trial of prophylactic isolated cytotoxic perfusion for poor-prognosis primary melanoma of the lower limb.

A randomized controlled trial of prophylactic isolated hyperthermic limb perfusion (IHLP) using melphalan at 2 mg/kg body weight has been performed on a total of 30 patients with primary melanoma of the lower limb > or = 1.7 mm thick. Excision (control, n = 14) was compared to excision plus IHLP (n = 16). The two groups were well matched for sex, tumour thickness and duration of follow-up (control group median: 63 months (range: 16-108), perfusion group median: 80 months (range: 37-113)). Recurrent disease developed in nine of the control group, seven of whom have died. In the perfusion group only two patients have developed recurrent disease, both of whom have died (recurrence: P < 0.004, mortality: P < 0.03, using Fishers' exact probability test). Inguino-femoral nodal recurrence occurred in five of nine control patients, but in only one patient in the perfusion group. These data support the use of adjuvant IHLP in the management of poor-prognosis primary melanoma of the lower limb.

Actuarial Analysis↗
PubMed1997

Ductal carcinoma in situ of the breast: the clinical significance of histological classification.

One hundred and twenty-one cases of ductal carcinoma in situ, including 26 cases with T1a invasive carcinoma, were reviewed. Seventy-nine patients (65%) were treated by mastectomy and 42 (35%) had conservative surgery. Ductal carcinoma in situ was classified as well differentiated (11%), intermediately differentiated (22%) or poorly differentiated (67%) according to nuclear morphology and the presence or absence of cell polarization. Poorly differentiated lesions were significantly larger than intermediately and well differentiated lesions (P = 0.03 and P = 0.01, respectively) and were significantly associated with the presence of extensive necrosis, marked periductal inflammation and periductal fibrosis (P < 0.0001). Invasive carcinoma was more common in the poorly differentiated group (25% compared with 18% in the intermediate group and 8% in the well differentiated group) but this was not statistically significant. The spectrum of differentiation was similar in symptomatic and mammographically detected ductal carcinoma in situ. Clinical follow-up was available in 90 patients (median period 45 months in patients who had undergone mastectomy and 23 months in those who had conservative surgery). Two incidences of recurrent local disease were recorded in the mastectomy group: one patient had well differentiated and the other poorly differentiated ductal carcinoma in situ. No local recurrences were observed in the conservative surgery group, possibly reflecting the shorter follow up period. All histological grades of ductal carcinoma in situ have the potential to progress to invasive carcinoma and mastectomy does not guarantee a cure.

Adult↗
PubMed1997

Laparoscopic cholecystectomy: incidental carcinoma of the gallbladder with abdominal wall and axillary node metastasis.

A case report is presented of intra-mural gallbladder carcinoma discovered incidentally after laparoscopic cholecystectomy who subsequently developed abdominal wall recurrence at the epigastric exit port, and axillary lymph node metastases. Possible preventative steps for tumour dissemination and a management plan if incidental carcinoma is diagnosed is discussed. The use of a non-porous retrieval bag, early recognition of the carcinoma and excision of the exit wound are advocated.

Abdominal Muscles↗
PubMed1996

Effect of growth factors on growth of bovine parathyroid cells in serum-free medium.

Published work has suggested a possible role of the epidermal growth factor receptor (EGFr) in parathyroid disease. Bovine parathyroid cells (BPCs) are frequently used as a tissue model for studying parathyroid disorders. We have studied the effect of the EGFr ligands EGF and transforming growth factor alpha (TGFalpha), alone and with insulin-like growth factors IGF-I and IGF-II on BPC growth. Experiments were run in triplicate and repeated three times. Cell numbers were assessed on day 5 by colorimetric MTT assay as well as by tritiated thymidine uptake. Results show that TGFalpha alone (p < 0.05) and IGF-I and IGF-II alone (p < 0.05) significantly stimulated growth over controls (t-test). Furthermore, the combination of TGFalpha with IGF-I and IGF-II exhibited significant enhancement above that seen with IGF-I and IGF-II alone (p < 0.01). EGF did not stimulate growth over controls. EGFr may be expressed in BPCs, but TGFalpha exhibits a more potent growth stimulus than EGF. Addition of IGF-I or IGF-II to the growth medium further enhances this effect.

Animals↗
PubMed1995

Blood flow in breast cancer and fibroadenoma estimated by colour Doppler ultrasonography.

Blood flow was measured by colour Doppler ultrasonography in 33 fibroadenomas of size 5-31 mm and 28 malignant breast masses of 8-37 mm visible on ultrasonography. There was detectable blood flow in 11 fibroadenomas and 21 cancers (P < 0.01). The median peak systolic frequency was 1.0 (range 0.25-2.0) kHz in malignant tumours and 0.5 (range 0.2-1.25) kHz in fibroadenomas. Blood flow was not detected in the eight fibroadenomas of less than 13 mm but was present in five of seven cancers smaller than this. Five of six carcinomas with three or more detectable vessels were classified as grade III on histological examination, compared with two of 11 carcinomas with one or two vessels. Similarly, five of seven cancers with three or more detectable vessels had axillary lymph node metastases compared with two of 13 with only one or two vessels. Detectable blood flow in breast masses is more common in cancer than in fibroadenoma and is highly suggestive of malignancy if the mass is less than 13 mm in size. Malignant tumours with a larger number of vessels are more likely to be of high grade and to have associated axillary node metastases.

Adolescent↗
PubMed1995

Metallothionein expression in duct carcinoma in situ of the breast.

In a previous study immunocytochemically detectable metallothionein (MT) expression in tumor cells of invasive duct carcinoma of the breast was shown to be associated with a more aggressive behavior and these findings have been subsequently confirmed by others. The aim of this study was to examine the prevalence and significance of MT positivity in preinvasive duct carcinoma in situ (DCIS). Fifty-five specimens of pure screen-detected DCIS were stained immunocytochemically for MT using the antibody E9. The intensity and distribution of MT staining were assessed using a semiquantitative method resulting in intensity distribution (ID) scores allowing duct by duct analysis in relation to architectural and cytological features of the DCIS. In general, myoepithelial cells around benign and malignant structures stained uniformly strongly for MT. Staining in DCIS was analyzed by architecture irrespective of cytology and by nuclear grade irrespective of architecture. The results showed that MT staining was significantly greater in comedo (ducts with necrosis) DCIS (ID = 97) compared with noncomedo (ducts without necrosis) DCIS (ID = 56) (P = .05 by Mann Whitney U statistic) and that low cytological grade (ID = 50) was associated with less MT staining than was high cytological grade (ID = 92) (P = .05 by Mann Whitney U statistic). These observations thus are consistent with the previously observed association between MT positivity and more aggressive behavior in invasive duct carcinoma of the breast.

Aged↗
PubMed1995

The satisfaction and savings of early discharge with drain in situ following axillary lymphadenectomy in the treatment of breast cancer.

A pilot study was performed to determine if early discharge with the drain in situ following axillary lymphadenectomy is feasible and safe. One hundred and one women who had axillary lymphadenectomy as part of their breast cancer treatment were studied. Ninety-six were offered early discharge with the axillary drain in situ, five were unsuitable for early discharge. The cohort who opted for early discharge (n = 39) had a lower rate of seroma formation (18% vs 34%) and a reduction in median hospital stay of 5 days. Patient satisfaction was high in both groups and there were no complications associated with early discharge or drain displacement. Early discharge after axillary lymphadenectomy with the axillary drain in situ is safe, feasible, popular with patients and offers considerable resource savings.

Adult↗
PubMed1995

Breast cancer management--a look forward. A view of breast cancer management in the United Kingdom in 1995 and the year 2000.

This paper endeavours to contrast the modes of presentation and techniques used in diagnosis and management policies of a 40-year-old woman with breast cancer at present, and as it is likely to be in the year 2000. An attempt is made to review the situation as it occurs across the UK at present, followed by an attempt to forecast how a similar patient is likely to be managed in the year 2000. The nature of the task inevitably involves generalizations, suppositions, hypotheses, informed guesswork and sheer speculation. The challenge is to stimulate thought and discussion among breast clinicians, so that appropriate and desirable changes may be anticipated, and consensus sought in utilising resources to move toward them.

Adult↗