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Biomedical subjects

I Taylor

Publications and source records attributed to I Taylor.

At least 145 records · Page 8Linked to original sources

Joubert syndrome associated with Leber amaurosis and multicystic kidneys.

We describe a boy with manifestations of Joubert syndrome, Leber congenital amaurosis, and multicystic kidneys. In infants with unexplained neonatal tachypnea and late developmental delay, absence or hypoplasia of the cerebellar vermis should be sought. Joubert syndrome probably is an autosomal recessive disorder. In the subsequent pregnancy of the propositus' mother, we were able to make a prenatal diagnosis of Joubert syndrome, one of the first to be reported.

Cerebellum↗

Increased risk of colorectal cancer associated with congenital anomalies of the urinary tract.

Two young mothers of children presenting with congenital anomalies of the urinary tract underwent colectomy for carcinoma or adenomatosis of the colon. In another family with urinary anomalies, the maternal grandmother had died from carcinoma of the colon at 36 years of age. This previously unreported associated led to two reviews. In the first, of 14 patients with colorectal cancer presenting under 45 years of age, three had known congenital urinary tract anomalies. In the second, which included the first three families, a detailed family history was obtained from children receiving treatment for congenital anomalies of the urinary tract. Seven of 116 grandparents and two mothers among 58 parents had colorectal carcinoma or adenomatosis of the colon; this was significantly greater than the expected incidence. A family history of congenital anomalies of the urinary tract may be a useful marker in screening for colorectal cancer.

Adult↗

Assessment of the value and pattern of use of a target controlled propofol infusion system.

Thirty one anaesthetists were supplied with a pharmacokinetic based target controlled propofol infusion system for evaluation. Twenty seven of 30 replies to a questionnaire sent to them indicated that the system had changed their use of propofol for maintenance of anaesthesia. The main reasons were greater ease of use and more confidence regarding the predictability of anaesthetic effects compared with manually controlled infusion. Data obtained from 770 patients anaesthetised with the system were analysed. The median maximum target concentration selected was 6.6 micrograms/ml. Younger patients (18-35 yr) required significantly greater target concentrations than older patients (65-80 yr). The mean time during which the system was in maintenance mode, when the predicted blood concentration of propofol was held constant for at least one minute, was 26.1 minutes. The median number of alterations in propofol concentration was 6. The target controlled infusion system provided an inexpensive and acceptable method of delivering intravenous anaesthesia.

Adolescent↗

Determination of Ki67 growth fraction and oestrogen receptors in screen-detected breast cancer using cytological preparations.

Oestrogen receptor (ER) status of 77 cases of screen-detected breast cancer has been determined using cytological preparations. In 48% ER status was positive, which was the same proportion as that formed in a control group of age-matched patients with symptomatic breast carcinoma. Since the screen-detected group contained more low grade tumours, the percentage of ER-positive cases would be expected to be higher. The reasons for the discrepancy are discussed. Ki67 score has been determined for 41 cases of screen-detected cancer. Ki67 score showed a positive correlation with histological tumour grade and a negative correlation with ER status. However, there was no correlation with tumour size or lymph node status. The Ki67 scores in the screen-detected cancers were essentially similar to those found in an age-matched symptomatic group, but the very low scores were only found in the screened group.

Biopsy, Needle↗

Study of the proliferation in human gastric mucosa after in vivo bromodeoxyuridine labelling.

Studies to measure human gastric crypt or gland cell proliferation may have a number of practical clinical applications in relation to both benign and malignant gastric conditions. Bromodeoxyuridine (BrdUrd) labels human gastric mucosal cells in the S phase. Computer aided data analysis of labelled mucosa allows static proliferative indices to be estimated, including the crypt labelling index (LI), the peak labelling position, the distribution of labelled cells and indirectly the crypt growth fraction. Multiparameter flow cytometric analysis of labelled nuclei allows the S phase duration (Ts) of mucosal cells to be estimated. Specimens of histologically normal gastric body (GB, n = 16) and antral mucosa (GA, n = 10) were obtained from 25 patients with gastric carcinomas who received a bolus dose of 250 mg BrdUrd between 3.0 and 15.7 hours before surgery. Tissue sections were stained by an immunohistochemical method and subjected to detailed counting of up to 50 longitudinal crypts per specimen. The total crypt labelling index was calculated by a grid counting method. A significant difference existed between the proliferative compartments of gastric antral and body mucosa measured by a number of criteria. The median lengths of the crypts were 137 cells (GB) and 188 cells (GA). The median peak labelling positions were cell 26 (GB) and cell 61 (GA) from the crypt orifice. The mean crypt labelling indices were 2.8% (GB) and 4.8% (GA). The mean Ts of GA cells was 7.7 hours and of GB cells was 10.8 hours.

Adult↗

Free peritoneal tumour cell identification in patients with gastric and colorectal cancer.

The finding of free tumour cells within the peritoneum at the time of laparotomy for gastrointestinal cancer is an important indicator of prognosis and may help select treatment. The aim of this study was to improve the methods whereby these cells could be retrieved and identified. Free peritoneal cancer cells were found in 6 out of 18 gastric cancer patients. All 6 patients had tumour invasion through to the serosa and subsequently died of tumour recurrence. None of the 18 Dukes' B and C colorectal cancer patients had free peritoneal cancer cells. Only 2 of a further 5 patients with extensive colorectal tumour spread had positive cytologies. The conventional mucin stain Periodic Acid Schiff (after diastase digestion) and the monoclonal antibody stain B72.3 were the most useful in identifying free peritoneal cancer cells. Peritoneal brushings did not offer any advantages over conventional peritoneal washings in the retrieval of free tumour cells.

Adult↗

Management of screen-detected breast cancer: audit of the first 100 cases in the Southampton and Salisbury breast screening programme.

With the natural history and optimal treatment of a high proportion of screen-detected breast cancers yet to be determined, treatment poses the management team with a number of therapeutic dilemmas. This study surveys the management policy and treatment of a consecutive series of 100 screen-detected cancers treated in a single breast unit. The problems encountered are discussed. There were 87 women with stage Tis or T1 tumours, including 26 women with in situ cancers, four with invasive cancers less than 5 mm in size, and seven with tubular cancers. Sixty-six women were managed with breast-conserving surgery and 36 women underwent localisation biopsy as the sole surgical treatment of the breast. With selection bias for high-grade and lateral tumours, only 2/13 cancers up to 10 mm in size were lymph node positive on axillary clearance. All lymph node positive women received adjuvant therapy. No adjuvant therapy was given in 43 cases, including those with in situ cancer. Thirty-six had extensive intraductal component (EIC). Patient and surgeon choice tends to be a major factor both in type of surgery and adjuvant therapy for screen-detected breast cancer. The optimal treatment for tumours detected by breast cancer screening is debatable and randomised trials on their management need to be expedited.

Breast Neoplasms↗

Breast size and prognosis in early breast cancer.

The influence of breast size on the prognosis of 196 patients with early breast cancer diagnosed in the period 1984-1985 was studied. Breast size was based on the volume from mammography. This method was validated against the volume of the mastectomy specimen determined by water displacement in 18 patients and found to be accurate (r = 0.93, P < 0.01). The median breast volume was 833.5 cm3 (interquartile range 522.8-1153.3 cm3). Breast size was significantly associated independently with age (Spearman's rank r = 0.24. P = 0.001), menstrual status (z = -4.81, P < 0.001), body weight (Spearman's rank r = 0.61, P < 0.001), T stage (z = -1.91, P = 0.05) but not N stage (z = -1.64, P = 0.10) or hormone receptor status (z = -0.80, P = 0.42). In an analysis of breast size and other known prognostic factors, based upon Cox's proportional hazards regression, N stage was the only significant factor for both breast cancer survival and disease-free survival. Even though women with larger tumours at presentation had larger breasts, breast size was not a significant prognostic factor in early breast cancer.

Age Factors↗

Axillary nodal status in women with screen-detected breast cancer.

A prospective study of the axillary nodal status of women found to have an invasive breast cancer within the prevalence screening round is reported. Thirty-one per cent of patients were lymph node positive. Twenty-two per cent of patients with an impalpable tumour and 41% of those with a palpable tumour had involved axillary lymph nodes. Only 6% of patients with a tumour of less than 10 mm had diseased axillary nodes. Of the factors examined only the size of the invasive component of the primary tumour was related to the axillary lymph node status. This proportion of patients with positive lymph nodes is higher than might be expected and is likely to represent those patients with potentially symptomatic breast tumours detected by breast screening in the first round.

Aged↗

Life events and breast cancer prognosis.

OBJECTIVE: To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN: Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING: Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS: 204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES: Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS: After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION: These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.

Breast Neoplasms↗

High-level expression of the cloned genes encoding the subunits of and intact DNA methyltransferase, M.EcoR124.

We have cloned the genes coding for the two subunits (HsdM and HsdS) of the type-I DNA methyltransferase (MTase), M.EcoR124, into the specially constructed expression vector, pJ119. These subunits have been synthesized together as an intact MTase. We have also cloned the individual subunit-encoding genes under the control of the T7 gene 10 promoter or the lacUV5 promoter. High levels of expression have been obtained in all cases. While HsdM was found to be soluble, HsdS was insoluble. However, in the presence of the co-produced HsdM subunit, HsdS was found in the soluble fraction as part of an active MTase. We have partially purified the cloned multi-subunit enzyme and shown that it is capable of DNA methylation both in vivo and in vitro.

Amino Acid Sequence↗

Purification and biochemical characterisation of the EcoR124 type I modification methylase.

Large scale purification of the type I modification methylase EcoR124 has been achieved from an over-expressing strain by a two step procedure using ion-exchange and heparin chromatography. Pure methylase is obtained at a yield of 30 mg per gm of cell paste. Measurements of the molecular weight and subunit stoichiometry show that the enzyme is a trimeric complex of 162 kDa consisting of two subunits of HsdM (58 kDa) and one subunit of HsdS (46 kDa). The purified enzyme can methylate a DNA fragment bearing its cognate recognition sequence. Binding of the methylase to synthetic DNA fragments containing either the EcoR124 recognition sequence GAAN6RTCG, or the recognition sequence GAAN7RTCG of the related enzyme EcoR124/3, was followed by fluorescence competition assays and by gel retardation analysis. The results show that the methylase binds to its correct sequence with an affinity of the order 10(8) M-1 forming a 1:1 complex with the DNA. The affinity for the incorrect sequence, differing by an additional base pair in the non-specific spacer, is almost two orders of magnitude lower.

Anilino Naphthalenesulfonates↗

Incidence of arm swelling following axillary clearance for breast cancer.

Arm swelling was measured using volume determination in 118 patients following mastectomy (n = 60) or wide excision (n = 58), both with axillary clearance. The mean age was 60.5 years and the median follow-up was 22.5 months. Axillary clearance removed level III nodes. Axillary irradiation was given to only three patients with extensive (more than 75 per cent) nodal involvement. The incidence of early postoperative complications was 18.6 per cent. The incidence of lymphoedema was 7.6 per cent (nine patients). Three of these patients had early lymphoedema within 6 months of treatment. Arm circumference differences correlated poorly with volume differences. The incidence of lymphoedema following axillary clearance is low and comparable to that for sampling or no axillary surgery.

Adult↗

Proliferation indices of invasive breast carcinomas after in vivo 5-bromo-2'-deoxyuridine labelling: a flow cytometric study of 75 tumours.

In vivo labelling of human breast tumours with 5-bromo-2'-deoxyuridine and analysis of proliferation by multiparameter flow cytometry is a new tool by which the labelling index, S phase duration (TS) and potential doubling time (Tpot) of the tumour can be estimated. Tumour specimens from 75 patients with invasive breast carcinoma were studied. Six tumours could not be analysed, and the TS and Tpot values could not be calculated for a further 18. The median labelling index (n = 69) was 4.2 per cent. The median TS (n = 51) was 8.7 h and the median Tpot (n = 51) was 8.2 days. The median intra-assay coefficient of variation for determination of the labelling index was 0.29 in five tumours. There were no significant differences in the total labelling index, TS or Tpot when patients were stratified according to lymph node status, tumour size, tumour grade or menopausal status.

Adult↗