Oxygen transport by a modified haemoglobin solution (PPSFH) in a dog model of acute anaemia following hypovolaemia.

Polymerised pyridoxylated stroma free haemoglobin (PPSFH) is a potential red cell substitute. We compared PPSFH to Succinylated Gelatin (SG) and autologous fresh blood (AFB) in a dog model. Three groups of dogs were subjected to a period of fluctuating hypovolaemia. Eight received AFB and had a final haematocrit (Hct) of 54% and total active haemoglobin level (WBod Hb) of 16.5 g/dl. Eight received SG, had a final Hct of 20% and WBod Hb of 5.6 g/dl. Eight received PPSFH, had a final Hct of 20% and a WBod Hb of 10.4 g/dl. Those dogs receiving AFB responded to the hypovolaemic stress by raising oxygen consumption by 27%, whereas in both those receiving SG and PPSFH, oxygen consumption fell by 15% (p = 0.007). In the PPSFH group the PPSFH carried 43% of oxygen consumed. Thus, although PPSFH provided a higher circulating haemoglobin level than SG and carried a high proportion of oxygen consumed, it did not confer any advantage in terms of bulk oxygen transport.

The prognostic significance of marrow micrometastases in women with early breast cancer.

Twenty-five patients with early breast cancer (T0-T2, N0-N1, M0) have been studied prospectively to determine the relationship between marrow micrometastases, disease-free interval and survival. Marrow specimens were aspirated from three sites immediately prior to breast surgery. An immunocytochemical technique using monoclonal antibody LICR.LON.M8.4 was employed to detect micrometastases. The minimum follow-up was 38 months. Twelve of the 25 patients (48%) had micrometastatic lesions in their marrow at presentation. Four of these patients developed distal recurrence during follow-up, causing death in two of them. Five of the 13 patients with no evidence of micrometastases developed distant recurrence and four of them have died. There was no correlation between the state of the marrow and the development of metastatic disease, although axillary lymph node status, disease stage and tumour volume correlated significantly with outcome (all P less than 0.025). Micrometastatic lesions appear to be common in the marrow of patients with early breast cancer. We have been unable to demonstrate that they have prognostic significance.

Vimentin expression does not assist in predicting survival in ductal carcinoma of the breast.

AIMS: To establish the value of vimentin expression in predicting survival in patients with breast cancer. METHODS: Five-year follow-up data were obtained for 68 patients with ductal carcinoma (NOS) of the breast in whom vimentin expression had been studied in fresh frozen and formalin-fixed, paraffin-embedded tissue. The predictive value on survival of tumour size, growth fraction (as assessed using the Ki67 monoclonal antibody), oestrogen receptor status and Bloom and Richardson grade of the primary tumour, and the presence or absence of lymph node metastases in axillary samples, were also studied. RESULTS: Twenty-two patients died of their disease within 5 years of diagnosis. Vimentin expression either on frozen or paraffin sections did not provide a statistically significant prediction of survival. On univariate analysis tumour grade, size and the presence of lymph node metastases provided prognostic information. Only lymph node status was of independent prognostic importance on multivariate analysis. CONCLUSIONS: Whilst these results confirm the value of established prognostic factors, they do not support the use of vimentin expression in either fresh or fixed tissue for the prediction of survival in ductal carcinoma (NOS) of the breast.

Auditing perioperative mortality.

An audit of mortality following operation was performed over ten years classifying deaths into those that were 'expected' and 'unexpected'. 'Unexpected' deaths were defined as those in which, after careful consideration of the prevailing clinical circumstances at the time of operation, the probability of death following operation was felt to be low. This definition is a more helpful assessment of surgical performance than overall perioperative mortality as it highlights cases where improvements in surgical management might be achieved. In audits involving surgical mortality, the classification of deaths into 'expected' and 'unexpected' is recommended.

Evaluating the breast screening programme: the need for surgical audit.

It is to be anticipated that a reduction in population mortality attributable to mammographic screening would be heralded by an increasing proportion of breast cancer cases diagnosed at earlier stages and by an improvement in case fatality. Few cancer registers routinely produce incidence or survival data by stage at diagnosis and thus improvement in these will be the harder to assess. By thorough casenote review and follow up, this study has determined the usual presentation and survival of breast cancer in Northern Ireland in 1986 before the introduction of screening. Overall, 85% of cases were Manchester stage I or II, figures which accord with other British studies. Five-year survival ranged from 77.8% for stage I (95% confidence limits 71.7%, 82.7%) to 35.7% for stage IV (95% confidence limits 13.0%, 59.4%). Forty-three per cent of cases treated in non-teaching hospitals could not be pathologically staged, more than twice the figure for teaching hospitals (Chi-squared = 15.7, df = 1, P < 0.001). Since many tumours not detected by screening will be treated outside teaching centres, this difference will reduce the statistical power to detect the true shift in stage distribution and improvement in survival from screening. Comprehensive surgical audit would help to resolve the inadequacies in existing data collection and improve the ability to evaluate the outcome of the screening programme.

Hereditary breast cancer in Northern Ireland.

The aim of this investigation was to document hereditary breast cancer in Northern Ireland. Family history details from over nine hundred women were obtained by postal survey and one hundred and twenty nine home visits were carried out to collect pedigree information. The families documented varied in the number of affected women from three, which was the minimum criteria for inclusion, to a maximum of nine and many families described other features of hereditary disease such as bilateral breast cancer, ovarian and gastrointestinal malignancies.

Do patients read breast self-examination booklets?

If a campaign to encourage women to examine their breasts for lumps is to succeed, it is necessary for women to read the literature produced. An attempt was made to estimate whether such literature was read, and in a group of women 90.6 per cent read the booklet, and 15.9 per cent altered their behaviour. There were several other non-numerical indicators which strongly suggested that women read the literature. A large-scale study is now under way.

The effect of complications on length of stay.

OBJECTIVES: The authors determined the effect of complications on length of stay (LOS) in surgical patients. SETTING: From 1987 to 1990, in the Professional General Surgical Unit of Royal Victoria Hospital, a retrospective survey was conducted on 5128 consecutively admitted patients with 396 different diagnosis; 228 different operations were examined. MAIN OUTCOME MEASURES: Patient LOS during a 3-year period in a general surgical ward was analyzed from hospital activity analysis, case notes, ward audit notes, and sepsis audit notes. Readmission rates for complications in patients with a short LOS were examined. Comparison were made between LOS and age, type of surgery, and complication type. RESULTS: Pressure on beds resulting from an increased demand on surgical care decreases patient's hospital LOS; increasing age increases LOS. In general, complications double the average LOS. The authors calculated that a surgical complication can be given a numerical ratio that directly reflects the severity of the complication and increases the patient's LOS. The ration of the infective complication corresponds with the clinical severity of the complication. However, a short LOS may lead to readmission of patients for further treatment. For patients readmitted with complications, 41% had been discharged earlier than the average LOS for their diagnosis. CONCLUSION: Length of stay is increased by complications and can be used to implement discharge planning in general surgical patients. Furthermore, a complication of their treatment can be given a numerical ratio that corresponds to the clinical severity of the complication and the increased LOS in hospital.

Pressure changes in varicose veins.

Pressures in the superficial leg veins of 24 patients with varicose veins and 6 normal controls were studied. In the controls there was no rise in pressure in the veins on increasing the intra-abdominal pressure, but in the patients with varicose veins pressure rose significantly. Squatting was no better than sitting in preventing transmission of intra-abdominal pressure to the leg veins. It was concluded that the difference in the positions adopted for defaecation is not the cause of the wide variation in the geographical distribution of varicose veins.

Detection of a vasoconstrictor factor in stroma-free haemoglobin solutions.

Polymerised pyridoxylated haemoglobin solution (PPSFH) is a modified haemoglobin solution which has a normal oxygen carrying capacity, long half-life, and reasonable oxygen affinity, and is a leading candidate for use as an oxygen carrying blood substitute. Previous work has given indications that vasoactive factors may be present. A bioassay sensitive to vasoconstrictors was constructed. PPSFH prepared by chloroform extraction produced a mean pressure rise of 24.3 mm Hg. PPSFH prepared by a crystallisation method showed a mean rise of 2 mm Hg (p = 0.0004). Unmodified stroma-free haemoglobin (SFH) prepared from platelet- and white cell-free red blood cells showed a mean rise of 32.5 mm Hg. These data indicate that both PPSFH and SFH contain a vasoconstrictor factor which is of low molecular weight, is hydrophilic, and is derived from red blood cells.

Confidence intervals and interval cancers ... needles and haystacks?

The measurement of interval cancer rates will be critical to the successful evaluation of the breast cancer screening programme. The number of interval cancers expected in a district will depend on the population size, the test sensitivity and the background incidence of breast cancer. The present study was undertaken to measure the incidence of breast cancer in Northern Ireland, and to assess the practical problems that might be encountered in ascertaining interval cancers. Given a local yearly incidence of 182/100,000, only 14 interval cancers per year might be expected in Northern Ireland (population 1.5 million). The completeness of the local cancer register would not ensure reliable detection of this relatively small number of tumours. To give larger samples sizes and thus narrow the confidence intervals of measured rates, the results from several smaller regions could be aggregated. Different regions may have different mechanisms of ascertainment and this may make the interpretation of these rates more difficult.

High colloidal uptake in axillary nodes with metastatic disease.

Axillary lymphoscintigraphy using 99Tcm antimony sulphide colloid has been carried out in 29 patients with suspected breast cancer and was correlated with histology. Of the 23 with proved tumour, axillary node metastases were found in 19 and, although 10 did have diminished uptake on the side of the lesion, 5 had an equal uptake in both sides and 4 had an increased uptake on the side of the lesion. Further, some of the nodes in which the high uptake had occurred were those heavily infiltrated by tumour. It is concluded that: a, lymphoscintigraphy with antimony sulphide colloid is not a reliable technique for the detection of metastatic disease in the regional nodes; b, any lymphoscintigraphy with this or any other agent requires more meticulous histological correlation than hitherto before it can be assumed to have any proved clinical value.

Does a booklet on breast self-examination improve subsequent detection rates?

Of 28 788 women aged 40 to 74 registered at 28 university teaching practices in greater Belfast, half were randomly selected to receive a booklet on breast self-examination from their general practitioner at the start of the study and 1 year later. The frequency of breast abnormalities was identical in both groups (0.83%) during the 2-year follow-up. Early malignant breast cancers (stages TX, TO, Tla) were significantly more frequent in the intervention group (53.6%) than in the control group (24.3%). Among women in the intervention group with malignant lesions, 2 sites, left nipple and left inner/upper quadrant, were significantly less frequently involved. These findings in relation to staging and site were confirmed by multivariate comparisons. The intervention group also had a smaller average tumour size (24.0 mm compared with 32.6 mm) due to significantly smaller benign tumours and the absence of the relationship between delay and tumour size evident in the control group.

Hereditary breast cancer and linkage analysis to BRCA1.

In this study, over 1000 women with breast cancer were contacted by questionnaire and 164 families with a strong history of breast cancer were identified. Home visits to obtain full pedigree details took place for 123 women, and members of 24 families gave venous blood samples. The extracted DNA was typed by polymerase chain reaction amplification and the derived haplotypes submitted to linkage analysis which confirmed that in 12 families breast cancer susceptibility could be traced to BRCA1. The study demonstrates the number of women at risk of breast cancer in the population, illustrates the complexity of genetic analysis for hereditary breast cancer and demonstrates the problems of predictive analysis in clinical management.

Thyroid hormones and selenium status in breast cancer.

Within a case-control study of postmenopausal breast cancer patients (n = 99) and matched healthy controls (n = 105), thyroid hormone levels were compared and correlated with toenail selenium concentrations. Plasma triiodothyronine (T3) was significantly lower in cases (1.4 +/- 0.4 nmol/l) than in controls (1.6 +/- 0.4 nmol/l), and a strong inverse relationship with breast cancer was observed with an odds ratio of 0.17 (95% CI = 0.08-0.36) in the highest compared with the lowest tertile of T3. Plasma thyroxine and thyroid-stimulating hormone concentrations were similar between cases and controls. Plasma T3 concentration was positively associated with toenail selenium in cases (age-adjusted regression coefficient = 0.049) and controls (age-adjusted regression coefficient = 0.036). Toenail selenium concentrations tended to be lower in cases than in controls, but the differences did not reach statistical significance. Although the disease process per se may explain the lower plasma T3 concentrations, it is also possible, inasmuch as these patients were in early-stage breast cancer, that selenium status may be influencing T3 levels via changes in the activity of the selenoenzyme type 1 iodothyronine deiodinase.