Naturally occurring double-stranded RNA and immune responses. III. Immunogenicity and antigenicity in animals.

Naturally occurring, double-stranded RNA (ds-RNA)) was immunogenic when injected into mice, rats, guinea-pigs, rabbits, dogs and baboons. The response to native material administered intravenously (i.v.) was strongest in rabbits and mice, and weakest in baboons. Mice, guinea-pigs and baboons injected with ds-RNA complexed with methylated BSA emulsified in Freund's complete adjuvant all gave high antibody responses. When ds-RNA was given in aerosol form to mice and guinea-pigs the response was weaker than that following i.v. injection, and baboons did not respond to antigen given as an aerosol. In most species the immune response obtained was predominantly IgM in nature, and there was no evidence for cell-mediated immunity in any species. The only evidence of an adverse reaction associated with repeated administration of ds-RNA was a systemic anaphylactic-type response in a small group of mice given ds-RNA repeatedly in aerosol form and challenged with ds-RNA i.v.     

An audit of long-stay patients in an inner city palliative care centre

An audit was carried out of patients with long admissions to a palliative care centre in central London. The records of patients remaining in the centre for more than 28 days were examined to see whether there were particular features characteristic of long-stay patients which could be identified to improve future admission planning.     

IgE antibodies to D. pteronyssinus in atopic patients.

An aqueous house dust mite extract was separated by SDS-PAGE and transferred to nitrocellulose membranes by Western Blotting. Two major allergens, Der pI and Der pII associated with the mite faeces and body, respectively, were identified on the protein blot. The blot was then probed with atopic sera and the bound antibodies were labelled with 125I anti-IgE and visualized by autoradiography. Using this technique it is shown that serum samples from eczema patients contain a higher proportion of anti-mite body IgE antibodies, whereas those from asthma patients contain a higher proportion of antibodies against the major mite faecal allergen Der pI. Minor mite body allergens are also shown to be important in eczematous patients. The role of mite allergens in atopic conditions is discussed, along with the significance of the findings presented here.     

Focal fits during chlorambucil therapy

An elderly man receiving chlorambucil for chronic lymphatic leukaemia developed focal fits. The onset and frequency were dose related. There was no evidence of metabolic disturbance or of meningeal leukaemia. Although reported in children and well recognized in animals, chlorambucil-induced fits in an adult have not been previously recorded.     

Hospice at home--a new service for patients with advanced HIV/AIDS: a pilot evaluation of referrals and outcomes.

Between 50 and 70% of patients with a terminal illness indicate a preference to remain at home for as long as possible until their death. Nevertheless, a much smaller percentage actually die at home in England and Wales. A new hospice-at-home service in North London for patients with HIV/AIDS is described in this report. Terminal care for HIV/AIDS patients can be provided at home by a multidisciplinary team which offers 24-hour care.     

An analysis of breast cancer surgery after free transverse rectus abdominis myocutaneous (TRAM) flap reconstruction

BACKGROUND: Breast reconstruction is currently offered on a more routine basis to patients after mastectomy for breast cancer. This paper analyzes the outcomes of breast cancer surgery, and the results and effects of breast reconstruction using free TRAM flaps. METHODS: A retrospective review of 75 consecutive patients who had free transverse rectus abdominis myocutaneous (TRAM) flap breast reconstruction after breast cancer surgery was performed. A total of 92 free TRAM flaps were performed on 75 patients in Victoria, British Columbia, from January 1992 to May 1999. Thirty-three patients (44%) underwent primary breast cancer surgery and an immediate reconstruction (7 bilateral and 27 unilateral) and 42 patients (56%) had delayed reconstruction (10 bilateral and 32 unilateral). RESULTS: Twenty- one patients (28%) had stage 0 disease, 20 (26.7%) had stage I disease, 17 (22.7%) had stage IIA disease, 12 (15%) had stage IIB disease, and 4 (5.3%) had stage IIIA disease. In 1 patient the stage of disease was unknown. The mean patient age was 49.4 years (range 33 to 73). Of the patients undergoing immediate reconstruction 3 had postoperative chemotherapy and 1 had postoperative radiotherapy. Three patients had combined chemoradiotherapy. In none of these cases was the adjuvant therapy delayed by the reconstructive surgery. Overall mean follow-up time from cancer diagnosis was 56.8 months and from the time of TRAM flap reconstruction, 36.7 months. To date, 5 recurrences have been detected (6.6%). Mean time between reconstruction and detection of recurrence was 22.8 months. Detection of recurrence was achieved clinically and was not impaired in any of the cases by the presence of the free flap. Patient satisfaction was assessed via a telephone survey, with 93% of patients pleased with the cosmetic results of their surgery. CONCLUSIONS: For those patients with breast cancer requiring mastectomy, free TRAM flap reconstruction is a safe, cosmetically acceptable surgical alternative that impairs neither effective breast cancer surgery nor detection of recurrent disease.     

Reforming higher specialist training in the United Kingdom--a step along the continuum of medical education

OBJECTIVES: The requirement to align the arrangements for postgraduate training in the United Kingdom with those elsewhere in the European Community provided the opportunity to review and reform our arrangements for higher specialist training. This paper describes the case for change--the strengths and deficiencies of the traditional pattern of postgraduate medical training, demographic influences in the medical workforce and the need for a more structural or planned approach to training. CONCLUSIONS: Over the past 5 years substantial progress has been made: the introduction of new regulatory arrangements and a new higher specialist training grade; the development of a managed and flexible system for delivering training to standards set by the Royal Colleges and which can accommodate the needs of those pursuing academic and research medicine; and the opportunity for trainees' progress to be measured against published curricula. The significant programme of change has been underpinned by careful workforce planning and the publication of comprehensive guidance. Significant reform of higher specialist training has been achieved. This paper also makes the case for a more strategic approach to planning and developing medical education across the continuum, from entry to medical school until retirement, which can guide medical education and improve patient care into the next millennium.     

Do men undergoing sterilizing cancer treatments have a fertile future?

This study was designed to assess the effect of cancer treatments on the natural and assisted reproductive potential of men. A cohort of men with cancer, in whom radiotherapy and/or chemotherapy was planned, were invited to participate. Twenty-two pre- and post-treatment semen samples were analysed. The reproductive potential of participants was assessed with respect to the current range of fertility treatment options available. Abnormal sperm concentrations were found in 27% of patients pre-treatment compared to 68% post-treatment following a mean latency of 20 months from treatment. Fifty-nine percent of patients experienced a clinically significant decrease in sperm, concentration following radiotherapy and/or chemotherapy; 23% developed azoospermia following treatment. Eighty-two percent of patients with testicular malignancy had oligo- or azoospermia post-treatment. Only one patient had a clinically significant reduction in the percentage of motile spermatozoa post-treatment. Cryopreservation of semen prior to treatment improved the fertility prospects of 55% of patients. Intracytoplasmic sperm injection (ICSI) enhanced the fertility prospects of a further 14%. In the absence of, or after depletion of, cryopreserved semen, ICSI could enhance the fertility prospects of 45% of patients. Fertilization has been achieved by ICSI using spermatozoa retrieved by testicular biopsy from an azoospermic testicular cancer survivor 8 years after chemotherapy. It was concluded that chemotherapy and/or radiotherapy may depress semen concentration to the extent of rendering a man infertile. The severity of the reduction in sperm concentration following treatment is unpredictable but likely to be most severe in those with testicular malignancy and those treated with radiotherapy or alkylating chemotherapy agents. Not all men are keen to undergo an appraisal of their post-treatment fertility potential, for reasons which are unclear. Improving awareness and education of patients concerning the effects of both cancer and cancer treatments on reproductive potential is essential. With the advent of ICSI, it is possible to offer a very reasonable chance of conception in all men with cancer who present for cryopreservation of semen prior to treatment in whom spermatozoa (even in very low concentrations) are present in the ejaculate.