The incidence and prevalence of systemic lupus erythematosus (SLE) in a well defined area in the Midlands was determined, by case ascertainment using multiple sources, during the period 1.5.89 to 30.4.90. This first such study of SLE in the UK showed incidence rates of 1.5/100,000/year for males and 6.5/100,000/year for females. The highest incidence was seen in age groups 40-49 and 50-59 years, with rates for females of 10.5 and 18.4/100,000/year respectively. Prevalence rates were 3.7/100,000/year for males and 45.4/100,000/year for females: SLE was found to be more prevalent amongst Afro-Caribbean groups. The socioeconomic status of the SLE patients was similar to the local study population, using social class by occupation and disadvantage by geographical area as indicators. Marked overlap between different sources of retrieval suggests that ascertainment of cases was high.

Objective-To investigate the incidence of ovarian failure after pulse cyclophosphamide treatment in systemic lupus erythematosus (SLE) and to compare this with two control groups: SLE patients treated with azathioprine, and a healthy age matched population. Methods-All women patients with SLE treated with pulse cyclophosphamide in our departnent were identified and questioned concerning menstrual history. All the hospital notes were reviewed and details recorded on dose of cyclophosphamide, duration of treatment, side effects and lowest pretreatment neutrophil and leucocyte counts during the course of treatment. Disease controls were recruited from our departnent and healthy controls from the local family health services authority (FHSA) register. Results-Incidence of ovarian failure in the premenopausal cyclophosphamide treated group was 54% and the incidence of premature menopause (occurring before age 40 years) was 41%. Increasing age at start of treatment showed a linear trend with incidence ofovarian failure (p = 0.01). Using logistic regression, increasing duration oftreatment was related to incidence of ovarian failure (p = 0 047 in those treated age 35 years or younger). An association between the lowest neutrophil count throughout the treatment period, when taken immediately before each planned cyclophosphamide pulse, and the incidence of ovarian failure was also demonstrated (p = 0 04 in those treated before age 40 years). Conclusion-Ovarian failure-in particular, premature failure after treatment with pulse cyclophosphamide-is common.

Nuclear transplantations into metaphase II (MII) and S phase oocyte cytoplasm were performed to investigate the influence of recipient cell cycle stage on nuclear function and development of bovine nuclear transplant (NT) embryos. Rate of inactivation of histone H1 kinase and duration of DNA synthesis in activated oocytes were determined. The proportion of S phase blastomeres in in vivo produced day 5.5 bovine embryos was measured. DNA synthesis was also assessed in NT embryos after transfer into MII and S phase cytoplasm. MII NT embryos were produced by fusing a blastomere into a MII oocyte; the fusion pulse served to activate the oocyte. S NT embryos were produced by fusing a blastomere into an early S phase oocyte electrically activated 4 h prior to fusion. Nuclear envelope structure, chromosome constitution, and extent of development were examined in MII and S NT embryos. Histone H1 kinase activity dropped to baseline within 2 h of electrical activation. A second electrical pulse did not alter H1 kinase activity when delivered 4 h after the first pulse. The frequency of S phase blastomeres in day 5.5 bovine embryos ranged from 79% to 100%, depending on the duration of culture in 3H-thymidine. Nuclear transplantation into MII cytoplasm resulted in a transient drop in DNA synthesis over 3.5 h. DNA synthesis resumed at 4.5 h post activation (hpa), concomittantly with initiation of DNA replication in activated oocytes. In contrast, DNA synthesis was not interrupted after transfer into S phase cytoplasm. DNA synthesis persisted until 13.5 hpa, as in activated oocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives-An analysis of the eYcacy of tacrolimus treatment in three patients with diYcult and severe systemic lupus erythematosus (SLE) whose active disease had been previously poorly controlled by cyclosporine and cyclophosphamide. Methods-A review of patient notes. Results-Two patients are well controlled after six and nine months of treatment with tacrolimus 0.06 mg/kg/day and 0.18 mg/kg/day. Previous persistent vasculitis had resolved and other features of active disease were controlled. The third patient's vasculitis had not improved significantly after two months of treatment and tacrolimus 0.17 mg/kg/day was discontinued because of nephrotoxicity. Conclusion-Tacrolimus may be a useful additional immunosuppressive agent in some patients whose SLE is not well controlled by conventional treatments.

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