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Biomedical subjects

S Nicholson

Publications and source records attributed to S Nicholson.

At least 91 records · Page 5Linked to original sources
PubMed1988

Use of fine needle aspiration cytology with immediate reporting in the diagnosis of breast disease.

Fine needle aspiration biopsy for cytological examination (FNAC) is becoming increasingly accepted as a means of tissue diagnosis in breast disease. This study examines the feasibility and accuracy of FNAC in 'immediate reporting' by a consultant cytopathologist in a busy breast clinic. Over a 2-year period, 884 cytology reports were analysed. An initial clinical report and subsequent final cytological diagnosis was made. Fine needle aspiration provided adequate material for cytological evaluation in 635 of the 884 biopsies (71.6 per cent) and this proportion was greater when discrete lumps were considered (463 of 562 biopsies = 82.4 per cent). In diffuse and cystic disease, however, the adequacy of specimens was reduced: 50 per cent and 65 per cent respectively. On immediate reporting the diagnostic sensitivity for all patients was 88 per cent (discrete lumps only, 92.5 per cent) and the specificity was 99.8 per cent (discrete lumps only, 100 per cent). FNAC retains its diagnostic accuracy when immediate reporting is employed and this study demonstrates that this technique can be used in making a diagnosis in patients with breast disease.

Biopsy, Needle↗
PubMed1988

Natural history of the benign breast lump.

A prospective study of 112 patients with clinically discrete benign breast lumps has shown that 68 per cent of patients experienced resolution of their lumps over a period of up to 2 years. Resolution of both fibro-adenomas and discrete areas of fibro-adenosis was observed. Diagnosis was achieved by clinical examination and fine needle aspiration cytology. Four patients thought clinically to have benign disease were proven by cytology to have a carcinoma, but no patient with a cytopathological diagnosis of benign disease has developed cancer during or subsequent to this study. We recommend that patients under 35 years of age with clinically and cytologically benign breast lumps can be offered the option of non-excision in the reasonable expectation of resolution of their lesion.

Adenofibroma↗
PubMed1988

Relationships between oestrogen receptor,epidermal growth factor receptor, ER-D5, and P24 oestrogen regulated protein in human breast cancer.

Proteins regulated by or related to the oestrogen receptor (ER) may prove to be more reliable indicators of prognosis and hormone sensitivity then expression of the receptor itself. It has been shown recently that expression of epidermal growth factor receptor (EGFR) is associated with a poor prognosis in breast cancer. In a series of 60 breast cancers, we have studied relationships between ER, ER-D5 oestrogen receptor related protein, P24 oestrogen regulated protein, and EGFR using an immunohistochemical technique employing monoclonal antibodies in each case. In addition, radioligand binding assays for ER and EGFR were carried out and tumour histological grade was determined. Seventy-one per cent and forty-three per cent of tumours stained for ER-D5 and P24, respectively, but there was no relationship between staining for these and ER or EGFR status. There was a significant correlation between staining for ER and EGFR, and the respective biochemical assays. Relating ER to EGFR, very few ER-positive cases expressed EGFR, but this relationship fell short of significance. The prognostic significance of expression of the epitopes recognized by the ERD5 and P24 antibodies must await assessment of clinical outcome.

Antibodies, Monoclonal↗
PubMed1988

Pulmonary hypoplasia testing in clinical obstetrics.

An ultrasound-based diagnostic test for predicting pulmonary hypoplasia antenatally by measurements of fetal chest circumference was applied prospectively to 45 patients at risk for developing this disorder. The outcome for the newborn infant and the autopsy findings were correlated with the antenatal prediction. The results of this test demonstrated a sensitivity and a specificity of 88% and 96%, respectively. The application of this test to clinical practice is recommended.

Amniotic Fluid↗
PubMed1988

Evaluation of fetal cardiac dysrhythmias with two-dimensional, M-mode, and pulsed Doppler ultrasonography.

Forty-three patients with fetal cardiac dysrhythmia were referred to a tertiary ultrasound department for further evaluation. The patients were subdivided according to the type of dysrhythmia diagnosed. All patients with irregular fetal heart rate had a good perinatal outcome. Of the six patients with fetal tachycardia, two required in utero therapy with maternal digoxin, and one of these fetuses had a cardiac tumor. The eleven patients with fetal bradycardia had the worst perinatal outcome, with four deaths occurring. The results suggest that all patients with fetal tachycardia or bradycardia should have a complete fetal cardiac assessment in a center experienced with the management of such cases.

Algorithms↗
PubMed1988

Atrial natriuretic peptide production in association with nonimmune fetal hydrops.

The presence and elevation of atrial natriuretic peptide in fetuses has not previously been demonstrated. This study of right atrial pacing in fetal lambs demonstrated a threefold to fourfold increase in atrial natriuretic peptide during the production of fetal hydrops. Its rate of return to a normal level paralleled the clearance of fetal hydrops. Its possible role in fetal cardiovascular hemodynamics is discussed.

Animals↗
PubMed1988

Epidermal growth factor receptor status of histological sub-types of breast cancer.

The histological breakdown of a consecutive series of 264 surgically resected malignant lesions of the breast was studied. Oestrogen and epidermal growth factor receptor status was quantified and presented along with size and lymph node status of the non-ductal lesions. Those non-ductal tumours containing EGF receptors have all recurred within two years of resection. Twenty-one percent of the lobular carcinomas contained EGF receptors compared to 34% of ductal carcinomas. EGF receptor status appeared to be associated with an increased risk of early recurrence and death whatever the histological sub-type of the breast cancer.

Breast Neoplasms↗
PubMed1988

Measurement of oestrogen receptor mRNA levels in human breast tumours.

A sensitive single-stranded hybridisation probe for the oestrogen receptor mRNA was synthesised using T3 polymerase from oestrogen receptor cDNA cloned in the Bluescript vector. This probe was used to measure oestrogen receptor mRNA in total RNA extracted from breast tumours. Oestrogen receptor mRNA was detected in 41 of 47 (87%) tumours whereas cytosolic oestrogen receptor protein was detected in only 18 out of 39 (46%). There was a significant correlation between the levels of the oestrogen receptor, as measured by 3H-oestradiol binding, and the oestrogen receptor mRNA. Oestrogen receptor mRNA was detected in 15 of the 21 tumours that did not contain detectable oestrogen receptor protein. This suggests that detection of the mRNA is a more sensitive means for establishing oestrogen receptor status than the radioligand oestrogen receptor assay. Oestrogen receptor mRNA was found in all histological tumour types examined. Its level was related to tumour differentiation. All the tumours that did not contain oestrogen receptor mRNA and most of the tumours that contained only low levels of oestrogen receptor mRNA were classified as grade III according to Bloom and Richardson: the median of the oestrogen receptor mRNA levels was significantly lower in this group.

Adult↗
PubMed1988

Epidermal growth factor receptor (EGFr) status associated with failure of primary endocrine therapy in elderly postmenopausal patients with breast cancer.

We have used primary endocrine therapy for 61 elderly women with operable breast cancer (median age 77 years). Eleven patients (18%) had complete and 24 (39%) partial tumour regression, 12 (20%) had stable disease for a minimum of six months and 14 (23%) no response. Salvage surgery was undertaken in the 14 with no response and 8/9 with progressive disease following initial response, thus samples were available from relapse patients only. Assays for EGFr (two point radioreceptor assay) and oestrogen receptors (ER) (dextran coated charcoal method and an immunohistochemical method) were performed on 20/22 patients. Ten of these 20 tumours were EGFr+ (greater than 10 fmol mg-1 binding) and 9/13 patients progressing within six months had EGFr+ tumours. 15/22 were available for ER evaluation and there was no such association with ER status. EGFr status was also associated with early recurrence after surgery and death in the endocrine failure group (P less than 0.005 and P less than 0.05 respectively). Of a control population of 33 patients (median age 72 years) treated by primary surgery, only 6 were EGFr+. In this group early relapse was predicted by EGFr status, but not by ER status (median disease free survival for EGFr+ patients 15 months, and for EGFr- patients 40 months, P less than 0.01, logrank test). There was a significantly higher proportion of EGFr+ tumours in the endocrine failure group compared with the control population (P less than 0.001). EGFr status is a marker for rapid early progression on primary endocrine therapy and the development of non-excisional methods of EGFr analysis would allow better directed therapeutic decisions.

Aged↗
PubMed1987

Properties of a multimeric protein complex from chloroplasts possessing potential activities of NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase and phosphoribulokinase.

A homogeneous multimeric protein isolated from the green alga, Scenedesmus obliquus, has both latent phosphoribulokinase activity and glyceraldehyde-3-phosphate dehydrogenase activity. The glyceraldehyde-3-phosphate dehydrogenase was active with both NADPH and NADH, but predominantly with NADH. Incubation with 20 mM dithiothreitol and 1 mM NADPH promoted the coactivation of phosphoribulokinase and NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase, accompanied by a decrease in the glyceraldehyde-3-phosphate dehydrogenase activity linked to NADH. The multimeric enzyme had a Mr of 560,000 and was of apparent subunit composition 8G6R. R represents a subunit of Mr 42,000 conferring phosphoribulokinase activity and G a subunit of 39,000 responsible for the glyceraldehyde-3-phosphate dehydrogenase activity. On SDS-PAGE the Mr-42,000 subunit comigrates with the subunit of the active form of phosphoribulokinase whereas that of Mr-39,000 corresponds to that of NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase. The multimeric enzyme had a S20,W of 14.2 S. Following activation with dithiothreitol and NADPH, sedimenting boundaries of 7.4 S and 4.4 S were formed due to the depolymerization of the multimeric protein to NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase (4G) and active phosphoribulokinase (2R). It has been possible to isolate these two enzymes from the activated preparation by DEAE-cellulose chromatography. Prolonged activation of the multimeric protein by dithiothreitol in the absence of nucleotide produced a single sedimenting boundary of 4.6 S, representing a mixture of the active form of phosphoribulokinase and an inactive dimeric form of glyceraldehyde-3-phosphate dehydrogenase. Algal thioredoxin, in the presence of 1 mM dithiothreitol and 1 mM NADPH, stimulated the depolymerization of the multimeric protein with resulting coactivation of phosphoribulokinase and NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase. Light-induced depolymerization of the multimeric protein, mediated by reduced thioredoxin, is postulated as the mechanism of light activation in vivo. Consistent with such a postulate is the presence of high concentrations of the active forms of phosphoribulokinase and NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase in extracts from photoheterotrophically grown algae. By contrast, in extracts from the dark-grown algae the multimeric enzyme predominates.

Chlorophyta↗
PubMed1987

Doppler ultrasound prediction of fetal outcome in twin pregnancies.

The usefulness of pulsed Doppler ultrasound in predicting twin pregnancies destined for unsatisfactory outcomes was examined in 30 twin pregnancies. Fetal flow velocity waveform analysis (systolic/diastolic ratio and pulsatility index) and quantitative analysis in the descending aorta and umbilical artery demonstrated good sensitivity and specificity when compared with biparietal diameter and abdominal circumference measurements. This technique shows some promise as a useful adjunct in the management of twin pregnancies.

Aorta, Thoracic↗
PubMed1987

Ultrasound evaluation of tachycardia-induced hydrops in the fetal lamb.

Nonimmune hydrops was induced in six fetal lambs at 120 days' gestation by right atrial pacing at 300 beats/min. Biochemical, hemodynamic, and Doppler parameters were observed and monitored by real-time ultrasound during the creation (18 to 42 hours) and resolution of hydrops. The significant changes seen were hypoproteinemia (34.3 to 29.0 mg/100 ml), venous hypertension (24.6 to 31.3 mm Hg), decreases in thoracic aorta flow, and decreases in systolic/diastolic ratios in the aorta and umbilical artery. These changes were reversed with the discontinuation of pacing and the resolution of fetal hydrops.

Animals↗
PubMed1987

Prolonged sensitisation of pituitary glands in vitro to repeated administration of luteinising hormone-releasing hormone: effects of pulse frequency, ovariectomy, estradiol and progesterone.

Anterior pituitary gland fragments were obtained from female Wistar-derived rats on dioestrus or pro-oestrus and perifused in Biogel columns in vitro. They were subjected at the beginning of each of 5 h of perifusion to a volley of 6 1-min pulses of luteinising hormone-releasing hormone (LHRH, 10 nM), given 4 min apart. Luteinising hormone (LH) was measured by radioimmunoassay in sequential 2-min fractions of the perifusate. Pituitary glands removed at 14.00 h on dioestrus showed a characteristic pattern of sensitisation followed by desensitisation to the repeated volleys of LHRH, whereas tissues removed at 10.00 or 14.00 h on pro-oestrus showed no evidence of desensitisation over the 5-hour period, the response to each LHRH volley being greater than the preceding one. Estradiol (E, 3-100 pg/ml) added to the medium from the start of perifusion had no significant effect on the pattern of response from tissues removed on pro-oestrus, but the highest concentration significantly enhanced the response of dioestrus pituitaries to all but the last of the LHRH volleys. Progesterone (P, 1-50 ng/ml) added to the medium produced a dose-related inhibition of the response of pro-oestrous tissues to the LHRH volleys. Groups of animals were ovariectomised (OVX) on dioestrus and used for experiment the next morning. OVX at 10.00 h on dioestrus produced the pattern of response characteristic of dioestrus the next morning, but with much higher levels of LH release, which were unaltered by the addition of E to the medium. OVX at 17.00 h on dioestrus produced an entirely different pattern of response the next day, with high basal and moderate LHRH-induced LH release, and no evidence of changes in sensitivity of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Permissive role for ornithine decarboxylase and putrescine in the luteinising hormone surge.

Anterior pituitary gland fragments removed from Wistar-derived rats at 10.00 h on pro-oestrus were perifused with Krebs-bicarbonate medium in a column and exposed to hourly volleys of 6 1-min pulses of 10 nM luteinising hormone (LH)-releasing hormone (LHRH). LH release showed a characteristic pattern of prolonged (over 5 h) sensitisation to the releasing hormone, with the response to each volley becoming progressively greater. The addition of 2 mM difluoromethylornithine (DFMO; an inhibitor of ornithine decarboxylase) to the perifusion medium completely inhibited the response to all volleys of LHRH. This effect of DFMO was reversed by the concurrent inclusion of 2 mM putrescine in the medium. Putrescine alone had a small but non-significant enhancing effect on LHRH-induced release, and no significant effect on basal LH release in this system. In a second series of experiments, tissues were loaded with 1-14C-ornithine and the radioactive carbon dioxide released into the medium during the perifusion monitored. Unstimulated pituitary tissues showed constant low levels of carbon dioxide release during 5 h of incubation, but those given hourly volleys of LHRH showed progressively increasing release of radioactivity, which was blocked by the addition of DFMO. No LHRH-stimulated increase in 14CO2 production from 1-14C-ornithine was seen from pituitary tissue removed at 10.00 h on dioestrus. Administration of DFMO (10-100 mg/rat) on the afternoon of pro-oestrus 4 h before the expected peak of the LH surge reduced the magnitude of the subsequent surge and the concentration of the hormone found in the anterior pituitary gland in a dose-related manner. In addition, the concentration of putrescine, but not of spermidine or spermine, was significantly reduced in treated animals (50 mg/rat) at the time of this attenuated surge.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗