Identification and treatment of anaemia in patients awaiting hip replacement.

INTRODUCTION: The correction of anaemia prior to total hip arthroplasty reduces surgical risk, hospital stay and cost. This study considers the benefits of implementing a protocol of identifying and treating pre-operative anaemia whilst the patient is on the waiting list for surgery. PATIENTS AND METHODS: From a prospective series of 322 patients undergoing elective total hip arthroplasty (THA), patients identified as anaemic (haemoglobin (Hb) < 12 g/dl) when initially placed upon the waiting list were appropriately investigated and treated. Pre- and postoperative Hb levels, need for transfusion, and length of hospital stay were collated for the entire patient cohort. RESULTS: Of the cohort, 8.8% of patients were anaemic when initially placed upon the waiting list for THA and had a higher transfusion rate (23% versus 3%; P < 0.05) and longer hospital stay (7.5 days versus 6.6 days; P < 0.05). Over 40% of these patients responded to investigation and treatment whilst on the waiting list, showing a significant improvement in Hb level (10.1 g/dl to 12.7 g/dl) and improved transfusion rate. CONCLUSIONS: Quantifying the haemoglobin level of patients when initially placed on the waiting list helps highlight those at risk of requiring a postoperative blood transfusion. Further, the early identification of anaemia allows for the utilisation of the waiting-list time to investigate and treat these patients. For patients who respond to treatment, there is a significant reduction in the need for blood transfusion with its inherent hazards.

Evaluation of quality of life and psychiatric morbidity in patients with malignant tumours of the skull base.

In general, patients with malignant tumours of the skull base have a poor prognosis. Treatment may have a disfiguring physical and disabling mental effect on patients. To evaluate the effect of treatment on physical and mental quality of life in patients with skull base malignancy, we conducted a cross-sectional patient survey of 18 patients treated for such tumours, using the University of Washington (version 4) quality of life questionnaire and the hospital anxiety and depression scale. The total quality of life score (median value) was 980 (550-1125). Patients with anterior skull base malignancy scored lower than those with lateral skull base malignancy (p=0.003). In general, the worst individual domain scores were: mood (64 per cent); activity (69 per cent); and, specifically for patients with anterior skull base malignancy, taste (54 per cent, p=0.004) and anxiety (60 per cent, p=0.034). One-third of skull base cancer patients were at risk of suffering from mental distress and psychiatric morbidity (indicated as a score of more than seven on the hospital anxiety and depression scale).

Direct detection of a microlens in the Milky Way.

The nature of dark matter remains mysterious, with luminous material accounting for at most approximately 25 per cent of the baryons in the Universe. We accordingly undertook a survey looking for the microlensing of stars in the Large Magellanic Cloud (LMC) to determine the fraction of Galactic dark matter contained in massive compact halo objects (MACHOs). The presence of the dark matter would be revealed by gravitational lensing of the light from an LMC star as the foreground dark matter moves across the line of sight. The duration of the lensing event is the key observable parameter, but gives non-unique solutions when attempting to estimate the mass, distance and transverse velocity of the lens. The survey results to date indicate that between 8 and 50 per cent of the baryonic mass of the Galactic halo is in the form of MACHOs (ref. 3), but removing the degeneracy by identifying a lensing object would tighten the constraints on the mass in MACHOs. Here we report a direct image of a microlens, revealing it to be a nearby low-mass star in the disk of the Milky Way. This is consistent with the expected frequency of nearby stars acting as lenses, and demonstrates a direct determination of a lens mass from a microlensing event. Complete solutions such as this for halo microlensing events will probe directly the nature of the MACHOs.

Dermatomyositis in association with transitional cell carcinoma of the bladder.

There is a well-recognized association between the inflammatory dermatomyopathy, dermatomyositis, and underlying visceral malignancy in adults. It is most commonly found in association with malignancies arising in the lung, breast and stomach. We report a case found in association with transitional cell carcinoma of the bladder, a site where there have only been a handful of previous reports.

Patients with cancer holding their own records: a randomised controlled trial.

BACKGROUND: The burden of cancer care in general practice is increasing. Patient-held records may facilitate effective, coordinated care, but no randomised controlled trials of their use in cancer care have been conducted, and concerns about possible negative effects remain. AIM: To evaluate the use of a supplementary patient-held record in cancer care. METHOD: Six hundred and fifty radiotherapy outpatients with any form of cancer were randomised either to hold a supplementary record or to receive normal care. It was explained to record holders that the supplementary record was intended to improve communication with health professionals and act as an aide memoire. After three months, patients' satisfaction with communication and with participation in their own care were assessed. Global health status, emotional functioning, and cognitive functioning were measured using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire. RESULTS: There were no significant differences between groups in any of the outcome measures. Patients in both groups expressed a high level of satisfaction with communication and participation in their care. Mean (SD) scores in the intervention and control groups were: global health status, 66.8 (24.2) and 65.3 (23.7); emotional functioning, 75.0 (24.6) and 77.4 (22.8); cognitive functioning, 84.5 (21.0) and 84.0 (21.3). CONCLUSION: A supplementary patient-held record for radiotherapy outpatients appears to have no effect on satisfaction with communication, participation in care, or quality of life.

The dark halo of the milky Way

Most of the matter in the Milky Way is invisible to astronomers. Precise numbers are elusive, but it appears that the dark component is 20 times as massive as the visible disk of stars and gas. This dark matter is distributed in space differently than the stars, forming a vast, diffuse halo, more spherical than disklike, which occupies more than 1000 times the volume of the disk of stars. The composition of this dark halo is unknown, but it may comprise a mixture of ancient, degenerate dwarf stars and exotic, hypothetical elementary particles.

Sensitivity of human squamous cell carcinoma of the larynx to fractionated radiotherapy.

Data obtained for the response of tumours from two multicentre clinical trials of the British Institute of Radiology have been combined and studied. Both trials involved patients with laryngopharyngeal carcinoma. There were 734 patients in the first trial, recruited between 1965 and 1975, and 611 patients in the second trial, recruited between 1975 and 1985. Observed survival and tumour-free rates for all patients are calculated. T-class and the nodal status of the patient at the start of the treatment were important factors in the determination of both observed survival and tumour-free rates. Overall treatment time was an important factor in determining the recurrence of tumour. The longer the overall treatment time the greater was the chance of tumour recurrence. The linear-quadratic (LQ) model was used in the analysis of the tumour recurrence data for a large group of patients with laryngeal tumours without nodal involvement. A small alpha/beta ratio of 0.94 Gy was obtained for T3 tumours while that of T2 tumours was negative, -10.5 Gy. The value for T1 tumours was higher at 23 Gy. However, use of the LQ model with a time component increased the alpha/beta ratios to 26.0 +/- 27.20 Gy, 18.0 +/- 12.33 Gy and 13.38 +/- 5.40 Gy for T1, T2 and T3 tumours, respectively. The time component, the gamma/alpha ratios, for these tumours were 0.15 +/- 0.27 Gy/day, 0.81 +/- 0.18 Gy/day and 0.76 +/- 0.15 Gy/day, respectively.

Lifespan of human lymphocyte subsets defined by CD45 isoforms.

The lifespan of thymic-derived or T lymphocytes is of particular interest because of their central role in immunological memory. Is the recall of a vaccination or early infection, which may be demonstrated clinically up to 50 years after antigen exposure, retained by a long-lived cell, or by its progeny? Using the observation that T lymphocyte expression of isoforms of CD45 corresponds with their ability to respond to recall antigens, we have investigated the lifespan of both CD45R0 (the subset containing responders, or 'memory' cells) and CD45RA (the unresponsive, or 'naive' subset) lymphocytes in a group of patients after radiotherapy. Here we report rapid loss of unstable chromosomes from the CD45R0 but not the CD45RA pool. Immunological memory therefore apparently resides in a population with a more rapid rate of division. Differing survival curves for the two subsets are best described by a model in which there is also reversion in vivo from the CD45R0 to the CD45RA phenotype. Expression of CD45R0 in T cells may therefore be reversible.

Carcinoma of the cervix uteri: an assessment of the relationship of tumour proliferation to prognosis.

The aim of this study was to ascertain whether assessing the growth fraction of cervical carcinoma of 28 patients, using antibody Ki-67, would be of value in clinical practice. The results showed no relationship between growth fraction and age, clinical stage, lymph node involvement or short term (3-5 years) survival.

Salvage surgery following irradiation with different fractionation regimes in the treatment of carcinoma of the laryngo pharynx: experience gained from a British Institute of Radiology study.

The 10-year follow-up of patients in a clinical trial involving the comparison of treatment by three fractions per week versus five fractions per week in radiotherapy of squamous carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. No statistically significant differences have been found between the two trial arms in terms of overall survival, age corrected survival, local recurrence, laryngectomy-free rates or effects on the normal tissues. Local recurrence was found in 320 of the 713 evaluable patients (45 per cent). Salvage laryngectomy was performed in 151 of the 320 patients with recurrence (47 per cent). Survival at 10 years for all node negative patients was 50 per cent in those patients without primary recurrence, compared with 40 per cent in those undergoing salvage laryngectomy.

Reduction in the diameter of human hairs following irradiation.

A measurable reduction in hair diameter was observed in human hairs following single exposures to gamma-rays, 250 KeV X-rays, 8 MV photons and 10 MV electrons in the range 2.9-14.0 Gy. The data from the different types of radiation were pooled and fitted by linear regression with a slope of 2.34 +/- 0.42% Gy-1. There was approximately 2.4% reduction in hair diameter per Gy exposure. It would appear that the measurement of damage to the matrix cells of growing human hairs exhibits potential for use in biological dosimetry, especially in cases of non-uniform overexposure.

Normal tissue reactions in the British Institute of Radiology Study of 3 fractions per week versus 5 fractions per week in the treatment of carcinoma of the laryngo-pharynx by radiotherapy.

The radiobiological data obtained from a multicentre clinical trial of the British Institute of Radiology, which compared the treatment of carcinoma of the laryngo-pharynx by 3 fractions per week (3F/wk) with 5 fractions per week (5F/wk) radiotherapy, have been studied. The trial involved an intake of 734 patients between 1966 and 1975. The number of fractions, overall treatment time and total doses used by different treatment centres ranges from 9 to 40 fractions, 18 to 70 days and 3880 to 7800 cGy, respectively. An 11-13% reduction in the total radiation dose was applied for treatments with 3F/wk as compared with 5F/wk in centres treating over 6 weeks and 3 weeks, respectively. All patients were followed for 10 years from the start of treatment. Different types of early and late normal-tissue reactions were investigated, ranging from a low percentage incidence of perichondritis to 95% for slight early reactions. Greater than 80% of the late normal-tissue reactions seen were observed within the first year after the start of treatment, and 96% were observed within the first 5 years. There was no statistically significant difference in the normal-tissue event-free rates between the 3F/wk and 5F/wk treatment groups. This finding did not differ when different major treatment centres were studied separately. For a number of end-points, alpha/beta ratios and N- and T-exponents of a modified nominal standard dose (NSD) formula have been calculated.

Final report on the second British Institute of Radiology fractionation study: short versus long overall treatment times for radiotherapy of carcinoma of the laryngo-pharynx.

The second British Institute of Radiology trial of dose fractionation in radiotherapy compared two groups of prospectively randomized patients with squamous carcinoma of the laryngo-pharynx; one group was treated in a short (less than or equal to 4 weeks) and the other in a long (greater than 4 weeks) overall time. Treatment in any one centre could be given, with no planned gap in the course of treatment, either as a conventional, daily (5 fractions per week regime) or as 3 fractions per week. A total of 611 patients were allocated to treatment, of whom nine have had to be excluded from the analysis for a lack of information. Patients were admitted to the trial from January 1976 to December 1985 and were followed up for a maximum of 10 years and a minimum of 3 years. A reduction in total dose was made for use in the short compared with the long treatment regime. This reduction in total dose varied between 18% and 22% depending on whether 5 fractions or 3 fractions per week regimes were used. Overall, no statistically significant differences have been found between the two arms of the trial. The patients treated with 5 fractions per week in a short overall treatment time showed fewer late normal tissue effects. An analysis based on stratification by age, stage and anatomical site gave a relative risk (short/long overall treatment time) for deaths of 1.23 with a 95% confidence interval from 0.96 to 1.59. Analyses stratified for stage and site gave relative risks with 95% confidence intervals of 1 x 10 (0.84-1.44) for local recurrences/tumour persistence, and 1.01 (0.70-1.45) for laryngectomies.

Recruitment, follow-up and analysis times in clinical trials of cancer treatment: a case study.

A study has been made of the way in which the number of events available for analysis in a clinical trial was dependent on the recruitment period, the maximum follow-up time on individual patients and the length of time between the start of the trial and its analysis. The events considered were deaths, local recurrences and late radiation effects on normal tissue in patients treated for cancer of the laryngo-pharynx by two different fractionation regimes. The relationship is demonstrated between the number of events and the 95% confidence intervals that can be placed on differences between results in the two arms of the trial. It was found, in this particular trial, that no significant improvement in precision was gained by following up patients beyond 5 years or carrying out the analysis later than 2 years after the end of recruitment. The results are discussed in the context of the initial design of clinical trials, particularly those in which the aim is to test therapeutic equivalence.

The predictive value of tumor classification compared with results of the British Institute of Radiology fractionation trial in the treatment of laryngopharyngeal carcinoma.

Data from a clinical trial involving 734 patients have shown the value and the deficiencies of the current Union Internationale Contre le Cancer's tumor, node, and metastasis classification system for prognostic purposes. The tumor-category classification provides a good discriminant for both nodal involvement and survival; however, the previous node classification system only discriminated between node-negative and node-positive patients, as nodal fixity was not found to be a discriminator. The current anatomical site classification is ambiguous for some laryngeal and pharyngeal subsites, and modifications to the present system based on prognostic values are proposed. A difference in patient age between tumor categories has been shown, and various differences in incidence and survival data for the sexes have been demonstrated. Differences in observed and expected survival rates are related to continued late deaths from tumor. Multivariate analyses have shown that stage grouping is the most powerful prognostic discriminator, followed by anatomical site and age.

Phase II studies of ifosfamide alone and in combination in cancer of the cervix.

A series of phase II studies using ifosfamide (IFX) as a single agent and in combination with cisplatin and bleomycin (BIP) in advanced and recurrent cervical cancer have been coordinated at the West Midlands CRC Clinical Trials Unit (Birmingham, UK). The aims of these studies were to identify single agents and combination regimens that may be of value for palliation and have potential for use as neoadjuvant and adjuvant therapy at the time of primary treatment. A total of 79 patients with disease non-amenable to radical local therapy were treated with single-agent IFX or the BIP combination. In 30 patients treated with single-agent IFX, 10 objective responses (30%) were seen, with 1 complete response. In 49 patients treated with BIP, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxicity included alopecia, nausea and vomiting, myelosuppression, infection, reduction in renal function and disturbance of consciousness. These data indicate that IFX is highly active in cervix cancer and, in combination with bleomycin and cisplatin, can be used for effective palliation and cytoreduction in greater than 70% of patients. IFX-containing regimens have potential for use as neoadjuvant and adjuvant therapy in patients at high risk of recurrence with conventional treatment. These hypotheses are currently being tested in prospective randomised trials.