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A D Hill

Publications and source records attributed to A D Hill.

At least 19 recordsLinked to original sources

The reactivity of 1,3-butadiene with butadiene-derived popcorn polymer.

Adiabatic calorimetry performed on butadiene-derived popcorn polymer samples from industrial facilities has revealed exothermic behavior accompanied by non-condensible gas production, indicative of possible decomposition, at elevated temperatures. In the presence of low concentrations of 1,3-butadiene, reactivity is observed at temperatures of 60-70 degrees C; that is, 20-30 degrees C below those usually seen for butadiene alone. Once the butadiene is consumed, the reaction behavior reverts to that of the popcorn polymer alone. At higher butadiene concentrations, the low temperature reaction persists, eventually merging with typical butadiene behavior. The butadiene reactivity with popcorn polymer is attributed to polymerization reaction at free radical sites in the popcorn polymer. Different popcorn polymer samples exhibit distinct extents of reactivity, presumably depending on the nature and concentration of the free radical sites and the structure of the material. Uninhibited butadiene exposed to 100 psia air, which may act to generate peroxide species, shows a small, additional exotherm around 50-80 degrees C. Contact of butadiene with lauroyl peroxide, providing free radicals upon decomposition, generates an exotherm at temperatures as low as 60 degrees C.

Air Pressure↗

Pathological axillary lymph nodes detected at mammographic screening.

AIM: To investigate the significance of abnormal axillary lymph nodes detected at mammographic screening in the absence of a concomitant breast lesion. METHODS: Twenty-three thousand, seven hundred and seven women were screened at the Merrion Unit as part of the Irish National Breast Screening Programme ("BreastCheck") in the period June 2000 to July 2002. Nine women (0.4 per 1000 women screened) were found to have an abnormal axillary lymph node(s) in the absence of a mammographic breast lesion and were recalled for assessment. The radiological criteria for recall included: size greater than or equal to 15 mm, round or irregular shape, increased node density and absence of hilar lucency. Each woman underwent further mammographic views, ultrasound examination of axilla and breast, clinical examination and lymph node biopsy either by 14G needle core biopsy (NCB) or open excision. RESULTS: The final pathological diagnoses in the nine patients were oestrogen receptor (OR) positive metastatic breast carcinoma (two patients), metastatic malignant melanoma (one patient), malignant lymphoma (two patients), caseating granulomatous lymphadenitis suggestive of tuberculosis (one patient), and other benign conditions (three patients). CONCLUSION: Abnormal axillary lymph nodes, in the absence of an accompanying breast lesion, are rarely identified on screening mammogram, but may harbour significant pathology and their presence on screening mammogram merits further investigation including biopsy.

Axilla↗

Prognostic importance of survivin in breast cancer.

Survivin is a member of the inhibitor of apoptosis (IAP) family, and is also involved in the regulation of cell division. Survivin is widely expressed in foetal tissues and in human cancers, but generally not in normal adult tissue. This study examined the expression of surviving protein in a series of 293 cases of invasive primary breast carcinoma. Survivin immunoreactivity was assessed using two different polyclonal antibodies, and evaluated semiquantitatively according to the percentage of cells demonstrating distinct nuclear and/or diffuse cytoplasmic staining. Overall, 60% of tumours were positive for survivin: 31% demonstrated nuclear staining only, 13% cytoplasmic only, and 16% of tumour cells demonstrated both nuclear and cytoplasmic staining. Statistical analysis revealed that survivin expression was independent of patient's age, tumour size, histological grade, nodal status, and oestrogen receptor status. In multivariate analysis, nuclear survivin expression was a significant independent prognostic indicator of favourable outcome both in relapse-free and overall survival (P<0.001 and P=0.01, respectively). In conclusion, our results show that survivin is frequently overexpressed in primary breast cancer. Nuclear expression is most common and is an independent prognostic indicator of good prognosis.

Adult↗

Elevated expression and altered processing of fibulin-1 protein in human breast cancer.

The extracellular matrix protein fibulin-1 suppresses the motility and invasiveness of a variety of tumour cell types in vitro as well as the growth of fibrosarcoma tumours in nude mice. In this study, fibulin-1 protein expression in breast carcinoma specimens and normal breast tissue was evaluated immunohistologically. Fibulin-1 protein expression was also semiquantitatively assessed by immunoblot analysis in a collection of normal breast tissues (n=18), benign tumours (n=5) and breast carcinomas (n=39). In normal breast tissue, fibulin-1 protein expression predominated in the ductal epithelium and underlying myoepithelium, with weaker staining evident in the loose connective surrounding the ducts. Examination of breast carcinomas revealed that the tumour cells also expressed fibulin-1 protein. The level of mature fibulin-1 polypeptide (100 kDa) was higher in the breast carcinoma specimens as compared to normal breast tissue (Mann-Whitney U-test, P=0.0005). In addition to the mature fibulin-1 polypeptide, several smaller sized polypeptides of 55, 50 and 25 kDa were detected using monoclonal antibodies reactive towards an epitope located at the N-terminus of fibulin-1. The immunoreactive 50 kDa polypeptide was detected more frequently in breast carcinoma specimens than in normal breast tissue (chi(2)=17.22, P<0.0001). Furthermore, the ratio of the 50 kDa fragment to the mature fibulin-1 polypeptide correlated with the level of oestrogen receptor alpha (Spearman correlation coefficient, rs=0.49, P<0.003, n=36) and progesterone receptor (rs=0.43, P=0.008, n=36) expression in the tumour specimens. Taken together, these findings indicate that elevated expression and altered processing of fibulin-1 is associated with human breast cancer.

Antibodies, Monoclonal↗

Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma.

BACKGROUND: Immunohistochemical analysis of sentinel lymph nodes from patients with breast carcinoma and melanoma has been shown to increase the sensitivity for detecting lymph node metastases. To the authors' knowledge, this technique has not been described in patients with Merkel cell carcinoma. METHODS: Lymphatic mapping and sentinel lymph node biopsy was performed on 26 patients with Merkel cell carcinoma between 1997 and 1999. All sentinel lymph nodes were analyzed with conventional hematoxylin and eosin (H&E) staining and then analyzed with immunohistochemical staining to evaluate whether this additional technique would increase the number of patients found to have lymph node metastasis. RESULTS: The median age of the patients in the current study was 67 years and the median tumor size at the time of presentation was 2 cm. Lymph node metastases were identified in 5 of the 26 patients (19%). Three of these five lymph node positive patients were identified with H&E staining. The remaining two patients were identified only after immunohistochemical analysis. The median follow-up in this group of lymph node positive patients was 14 months, with 2 of the 5 lymph node positive patients developing a recurrence. The median follow-up in the 21 patients who were lymph node negative was 19 months, with only 1 patient having developed a recurrence at the time of last follow-up. CONCLUSIONS: Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma appears to increase the sensitivity of detecting clinically occult lymph node metastases.

Adult↗

Studies on oestrogen receptor-alpha and -beta mRNA in breast cancer.

The oestrogen receptor (ER) is widely used to predict response to tamoxifen in patients with breast cancer. Recently a new form of ER known as ER-beta was discovered, the original ER is now designated ER-alpha. In this investigation, ER-alpha and ER-beta were measured in 107 breast carcinomas and 22 fibroadenomas. Using reverse transcriptase-polymerase chain reaction (RT-PCR), ER-beta mRNA, but not ER-alpha mRNA was expressed more frequently in fibroadenomas than carcinomas. In the carcinomas, ER-beta mRNA was present in a greater proportion of samples positive for ER-alpha mRNA than in those lacking this form of the receptor. ER-alpha, but not ER-beta mRNA, was significantly associated with ER protein-positivity in the cancers. ER-alpha mRNA was also positively related to progesterone receptors (PR), but ER-beta mRNA showed an inverse relationship with PR. We conclude that the presently used enzyme-linked immunosorbent assay (ELISA) for ER appears to be mostly measuring ER-alpha and is unlikely to be detecting ER-beta.

Biomarkers, Tumor↗

Prospective evaluation of the morbidity of axillary clearance for breast cancer.

BACKGROUND: Axillary clearance, despite its morbidity, retains an essential role in the management of patients with breast cancer. The aim of this prospective study was to document the development of arm swelling and limitation of shoulder movement following complete axillary clearance. METHODS: One hundred patients who had axillary clearance to level III, for treatment of breast cancer, were followed prospectively for over 1 year. Arm volumes were measured using an optoelectronic volometer and shoulder movements with a goniometer. RESULTS: Ten patients had significant arm swelling at 1 year. The swelling was mild in eight and moderate in two. No patient developed severe swelling. Reduced arm movements were noted in the first week after operation but had returned to normal at 6 months. CONCLUSION: This study provided accurate documentation of the morbidity associated with axillary clearance, together with a reproducible method of arm volume measurement.

Adult↗

Parathyroid carcinoma: diagnosis and management.

Parathyroid carcinoma is a rare and difficult diagnosis to make based on the histological features alone. We review five cases of parathyroid carcinoma in the past 30 years and the clinical and biochemical features that facilitate the making of the diagnosis. A favourable outcome can be expected with adequate surgical treatment.

Adult↗

Calcium fractional absorption and metabolism assessed using stable isotopes differ between postpartum and never pregnant women.

Determining the fractional absorption (FA) of calcium using the incorporation into urine of stable isotopes given intravenously (IV) and orally has become a routine procedure. We investigated the FA of calcium in two groups of (2-3 mo) postpartum women lactating (LACT) (n = 6) and nonlactating (PPNL) (n = 6), and in never pregnant (NP) women (n = 7). The women consumed a controlled diet containing 30-33 mmol/d calcium (Ca) for 21 d. On d 7 of the controlled diet, the women received 0.05 mmol of 42Ca IV and 0.25 mmol 44Ca orally in milk. Urine samples (24-h) were collected for the next 14 d and morning blood samples were collected from fasting subjects before dosing and at 24 and 48 h after receiving the isotopes. Milk samples from the LACT women were collected from each feeding beginning 24 h before to 72 h after dosing. There were no significant differences in the FA of calcium as measured by stable isotope incorporation into urine (23.8 +/- 2.9%), serum (24.0 +/- 3.4%) or milk (23.6 +/- 3.6%) of LACT women. The fractional calcium absorption measured in urine of the postpartum women (LACT and PPNL, 23.8 +/- 2.9% and 25.0 +/- 3.3%, respectively) did not differ but was greater (P < 0.028) than that of the NP women (17.3 +/- 1.3%). The postpartum LACT and PPNL women had a reduced urinary excretion of calcium (P < 0.01) compared with the NP women. There was a significantly greater incorporation (P < 0.001) by LACT women of the oral isotope dose into milk than into urine. Calcium FA can be determined from incorporation of stable isotopes into breast milk and serum as well as urine.

Absorption↗

Suppression of macrophage nitric oxide production by melanoma: mediation by a melanoma-derived product.

The tumour-bearing state is known to induce immune dysfunction that contributes to increased infectious complications and tumour progression. However, the mechanisms underlying this immunosuppression remain unclear. This study investigated in a murine model the effects of melanoma growth on nitric oxide (NO) production by peritoneal macrophages in vivo and in vitro. B16 and K1735 melanoma cells were inoculated subcutaneously into C57BL/6 and C3H/HeN mice, respectively. Stimulated NO production by elicited peritoneal macrophages was examined in control and melanoma- bearing mice. An in vitro system was established to assess the effects of co-culturing melanoma cells (B16 and K1735) or melanoma-conditioned medium with normal peritoneal macrophages on subsequent NO production. NO production was significantly suppressed in macrophages from melanoma-bearing mice. Co-culture of normal macrophages with melanoma cells in a transwell system or with melanoma-conditioned media in vitro reproduced the defects observed in vivo without affecting macrophage viability, pointing to a melanoma-derived product as the basis for the observed suppression of NO production. This inhibition required RNA and protein synthesis and was dose and time dependent. Using inhibition profiles and neutralizing antibodies, it was demonstrated that this melanoma inhibitory activity was distinct from known NO inhibitors. Preliminary characterization attributed this activity to a melanoma-secreted protein moiety.

Animals↗

Post-partum ovarian vein thrombosis.

Post-partum ovarian vein thrombosis (POVT) is uncommon, but the true incidence is not known. Ninety per cent of cases present as right iliac fossa pain within 10 days of delivery. Anti-coagulation and intravenous antibiotics are the mainstay of treatment. We report three cases that were referred to our unit. These cases illustrate the difficulty in the clinical diagnosis of POVT and highlight the importance of its inclusion in the differential diagnoses of an acute abdomen in post-partum patients. POVT can be accurately diagnosed by appropriate noninvasive investigations and a laparotomy avoided.

Adult↗

Bone-related mineral content of water samples collected on the Navajo reservation.

Although dairy food intake is low among the Navajo people, hip fracture rates are lower than in Caucasians. Genetic differences in bone density have been cited as the reasons for low fracture rates among Native Americans and other segments of the population. However, more detailed examination of mineral intakes suggests that environmental factors may provide part of the explanation for the lower fracture rates. Cultural practices such as the addition of ash to traditional foods and the high mineral content of water may provide much higher intakes of bone-related minerals than food intake surveys have previously reported. As part of a larger study to assess overall intake of minerals related to bone health and other conditions, water samples were collected from the Navajo reservation. Duplicates were collected at least one week apart from 53 sites including wells, springs, taps, and storage barrels and analyzed by atomic absorption and inductively coupled plasma spectrometry for a number of minerals. For average intakes of 2 l/day, water could provide up to 212 mg of calcium, 150 mg of magnesium and 8 mg of zinc. The combined contribution of mineral intakes provided by the addition of juniper ash to traditional foods, not genetic differences, may partially explain the lower fracture rates of the Navajo people. Further research in this area is required to confirm this hypothesis.

Bone and Bones↗

Tumour micrometastases: the influence of angiogenesis.

INTRODUCTION: Many cancer patients have undetected micrometastatic disease at first presentation which ultimately progresses. Angiogenesis-the development of an independent blood supply-is a key event in the growth of metastases. Improved understanding of the influence of angiogenesis on micrometastatic growth may lead to new therapeutic intervention. METHODS: This study examines current concepts of the significance of micrometastases and the role of angiogenesis in their development and destruction. A comprehensive review of the literature on micrometastasis and angiogenesis was performed using the Medline database between 1966 and 1999. CONCLUSIONS: Advances in technology have improved our ability to diagnose metastatic disease, but micrometastases in loco-regional lymph nodes and at distant sites can only be detected by sophisticated histological techniques. While the significance of micrometastases remains controversial, there is increasing evidence that micrometastatic status provides useful prognostic information and should be part of standard staging techniques. Anti-angiogenic therapy has the potential to favourably influence management of certain cancers by manipulating a number of key events in the metastatic process.

Bone Marrow Neoplasms↗

Sentinel lymph node biopsy in breast cancer: unfiltered radioisotope is superior to filtered.

BACKGROUND: The combination of gamma-probe radiolocalization and blue-dye mapping of sentinel lymph nodes (SLNs) has been advocated as the most accurate method for staging the clinically negative axilla in breast cancer patients, but the technical aspects of these procedures are not fully characterized in the literature. In this study, we compared the success of SLN localization in 134 consecutive breast cancer patients using blue dye plus two different preparations of radiocolloid. STUDY DESIGN: A retrospective analysis of a prospectively maintained data base was performed to assess SLN localization in two cohorts of patients. Unfiltered technetium-99m (Tc-99m) sulfur colloid (in 77 patients; group I) was compared with filtered Tc-99m sulfur colloid (in 57 patients; group II). All patients had a peritumoral injection of blue dye and isotope, followed immediately by lymphoscintigraphy to confirm radioactivity at the injection site and to image the SLN. Statistical analysis was performed using the Pearson chi-square test. RESULTS: Unfiltered Tc-99m sulfur colloid was superior to the filtered radiocolloid in localizing the SLN (88% versus 73%; p = 0.03). SLN imaging by lymphoscintigraphy was also more successful in the unfiltered group. Using the combination of blue dye and radiolocalization, SLNs were identified in 94% of patients. CONCLUSIONS: For optimal localization of the SLN in breast cancer patients, surgeons should use the combined technique of blue-dye mapping and gamma-probe localization using unfiltered Tc-99m sulfur colloid.

Biopsy↗

Intraoperative lymphatic mapping and sentinel lymph node biopsy for Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma is a rare cutaneous neoplasm which commonly spreads to the regional lymph nodes. The feasibility of identifying the sentinel node in patients with clinically node-negative Merkel cell carcinoma was evaluated. METHODS: Sentinel lymphatic mapping was performed in 18 patients with stage 1 Merkel cell carcinoma using the combination of isosulphan blue dye and 99mTc-radiolabelled sulphur colloid. Patients with tumour metastasis in the sentinel node underwent complete dissection of the remainder of the lymph node basin. RESULTS: Eighteen patients underwent removal of 35 sentinel nodes. Two patients demonstrated metastatic disease in the sentinel lymph nodes; complete dissection of the involved nodal basin revealed no additional positive nodes suggesting that the sentinel lymph node had been identified. The node-negative patients received no further surgical therapy, with no evidence of recurrent disease in the sentinel nodal basin at a median of 7 months' follow-up. CONCLUSION: Sentinel node biopsy is feasible in patients with Merkel cell carcinoma. It can be used to stage patients and provides important prognostic information. In those with subclinical nodal disease, it may direct early regional lymphadenectomy but the effect of such surgery on survival remains unclear.

Adult↗

Lessons learned from 500 cases of lymphatic mapping for breast cancer.

OBJECTIVE: To evaluate the factors affecting the identification and accuracy of the sentinel node in breast cancer in a single institutional experience. SUMMARY BACKGROUND DATA: Few of the many published feasibility studies of lymphatic mapping for breast cancer have adequate numbers to assess in detail the factors affecting failed and falsely negative mapping procedures. METHODS: Five hundred consecutive sentinel lymph node biopsies were performed using isosulfan blue dye and technetium-labeled sulfur colloid. A planned conventional axillary dissection was performed in 104 cases. RESULTS: Sentinel nodes were identified in 458 of 492 (92%) evaluable cases. The mean number of sentinel nodes removed was 2.1. The sentinel node was successfully identified by blue dye in 80% (393/492), by isotope in 85% (419/492), and by the combination of blue dye and isotope in 93% (458/492) of patients. Success in locating the sentinel node was unrelated to tumor size, type, location, or multicentricity; the presence of lymphovascular invasion; histologic or nuclear grade; or a previous surgical biopsy. The false-negative rate of 10.6% (5/47) was calculated using only those 104 cases where a conventional axillary dissection was planned before surgery. CONCLUSIONS: Sentinel node biopsy in patients with early breast cancer is a safe and effective alternative to routine axillary dissection for patients with negative nodes. Because of a small but definite rate of false-negative results, this procedure is most valuable in patients with a low risk of axillary nodal metastases. Both blue dye and radioisotope should be used to maximize the yield and accuracy of successful localizations.

Adult↗