Randomised trial of two embolic agents for uterine artery embolisation for fibroids: Gelfoam versus Embospheres (RAGE trial).

BACKGROUND: Uterine artery embolisation (UAE) is an established treatment option for women with symptomatic uterine fibroids who wish to avoid surgery. However the most efficacious embolic agent remains uncertain. METHODS: We conducted a pilot double blind randomized controlled trial comparing Gelfoam with Embospheres in women undergoing UAE. Outcomes recorded at baseline, 24-h, 1 and 6 months included complications, inflammatory, haematological markers and ovarian function. Contrast enhanced MRI (CEMRI) was acquired at baseline, 24-h and 6 months. Pain score (visual analogue) was measured at 24-h, quality of life (UFS-Qol) at baseline, 1 and 6 months. All patients were followed to 6 months. RESULTS: Twenty patients were randomized 1:1 to receive either Gelfoam (G) or Embospheres (E). The UFS-Qol symptom score improved in both groups at 6 months mean of 64 ± 18 to 23 ± 16 and 54 ± 15 to 32 ± 26 in the E and G groups respectively. UFS-Qol HRQL also improved in both groups at 6 months, mean 41 ± 28 to 79 ± 20 and 53 ± 19 to 78 ± 21 in the E and G groups respectively.Uterine volume at 6 months reduced from 1018 ± 666mls to 622 ± 436 (p = 0.001) and from 1026 ± 756 to 908 ± 720 (p = 0.15) in the E and G groups respectively. There was a significant difference between groups for this parameter p = 0.01. All uterine arteries were patent at 24-h and 6 months. Complete (100%) fibroid infarction rates were 5(50%) and 2(20%) in the E and G groups respectively. None of the other outcome measures showed any between group differences. There were no re-interventions in either group. CONCLUSION: The only significant between group differences was for a greater reduction in uterine volume at 6 months in the E group. A larger trial (estimate 172 subjects) is required to determine whether other apparent differences are clinically and statistically significant. TRIAL REGISTRATION: ISRCTN67347987.

Can (1)H MR Spectroscopy be Used to Assess the Success of Uterine Artery Embolisation?

PURPOSE: Absence of contrast on contrast enhanced MRI (CEMRI) and reduction in uterine volume at 6 months post-uterine artery embolisation (UAE) currently indicate the successful disruption of the fibroid blood supply by UAE. This study assesses whether (1)H MR spectroscopy ((1)H MRS) can also indicate the success of UAE. METHOD: 20 patients with symptomatic fibroids were randomised 1:1 to undergo UAE with either Gelfoam or Embospheres. CEMRI and spectra (1.5 T) were acquired pre-, 24-h and 6 months post-UAE. LCModel was used to detect significant levels of choline, creatine and lactate in fibroid spectra. Uterine volumes were measured and paired t tests (p < 0.05) assessed volume reduction over time. Qualitative assessments of CEMRI were performed. RESULTS: Choline was detected in 17/18 spectra pre-UAE, 12/14 at 24-h and 6/16 at 6 months post-UAE. Choline was not detected in the 7/7 spectra available for the Embospheres group at 6 months. These fibroids were non-enhancing on CEMRI and associated with a significant reduction in mean uterine volume at 6 months (mean/min/max 396.5/84.1/997.5 cm(3), p = 0.003). Choline was detected in 6/9 fibroid spectra available for the Gelfoam group at 6 months. Of these fibroids, four demonstrated persistent enhancement on CEMRI and two were non-enhancing. This group did not demonstrate significant uterine volume reduction (mean/min/max 117.2/-230.6/382.6 cm(3), p = 0.15). The negative minimum value indicates fibroid growth. CONCLUSIONS: This study has demonstrated the potential of (1)H MRS to provide an additional marker of the success of UAE.

Cardiomyopathy in pregnancy and caesarean section: four case reports.

We present the clinical details of four women with cardiomyopathy who required caesarean section. Two women had peripartum cardiomyopathy and two had hypertrophic obstructive cardiomyopathy, one of whom has had two caesarean sections. Those with peripartum cardiomyopathy were more compromised than those with hypertrophic obstructive cardiomyopathy. Co-operation between obstetric and cardiac anaesthetists ensured optimum experience was available. An incremental combined spinal-epidural technique with invasive monitoring was used for three women and one received general anaesthesia. The risks and benefits of different anaesthetic techniques are discussed.

A structured approach to the interpretation and reporting of ventilation/perfusion scans.

The aim of this study was to develop a structured approach to the reporting and in particular the clinical interpretation of ventilation/perfusion (V/Q) scan results. An initial audit indicated that there were significant variations in the clinical management of patients particularly after a non-diagnostic V/Q scan report. There were also differences in the approaches used to interpret the scan itself. In an attempt to improve this, a set of interpretation guidelines was produced based on the revised PIOPED data. To combat the problems with clinical interpretation, a standard method for assessing the pre-test clinical probability of pulmonary embolism was established. This clinical risk was then combined with the V/Q scan result to give an overall probability for the presence of pulmonary embolism. The more precise risk stratification which resulted allowed explicit clinical advice on patient management to be incorporated into the final report. A second audit was performed with the revised methodology in place. The level of inter-observer variability for scan reporting decreased from 30% to 12%. The prior assessment of clinical risk and the standardized method of combining this with the scan result led to an improvement in patient management. This was particularly true for the non-diagnostic group, in whom additional investigations were more appropriately used. A structured approach which allows the pre-test probability of pulmonary embolism to be combined in an explicit fashion with the V/Q scan result can provide a more precise risk stratification allowing appropriate recommendations to be made. Such an approach can result in improved patient management.

How would patients prefer to spend the waiting time before their operations?

Many surgical patients are anxious while waiting to go to the operating theatre in spite of the best preparation with drugs, information and reassurance. It is possible that patients could be more comfortable if allowed a choice of activities before operations. The objective of this study was to find out how pre-operative patients might prefer to occupy their time. We distributed 200 questionnaires to elective surgery patients and 184 (92%) were available for analysis. Of the respondents, 54.1% wanted to be slightly sleepy, 72.0% preferred not to be fast asleep and 57.2% preferred not to be wide awake. Reading (56.8%), listening to music (57.1%) and chatting with other patients (39.9%) were preferred activities. It might be appropriate to ask patients how sedated they would wish to be before their surgery and perhaps have alternatives to sedation available.

Endometrial status in post-menopausal women on long-term continuous combined hormone replacement therapy (Kliofem). A comparative study of endometrial biopsy, outpatient hysteroscopy and transvaginal ultrasound.

Forty post-menopause women using a preparation of 2 mg 17 beta-oestradiol and 1 mg norethisterone acetate (Kliofem) for a mean duration of 2.9 years were investigated in an open, prospective, method comparison study. Main outcome measures were the histology of endometrial biopsy in comparison with clinical evaluation of the endometrium during panoramic hysteroscopy and endometrial thickness measured by transvaginal ultrasound. Thirty-six women had either an inactive atrophic or unassessable endometrial biopsy, the remaining four (10%) showed benign endometrial changes. In the majority of patients the endometrium had a thin and regular appearance on hysteroscopy (92.5% of cases) with an endometrial thickness not exceeding 7 mm (90% of cases). Non-agreement between histology and hysteroscopy or transvaginal ultrasound findings was associated with the presence of polyps and submucosal fibroids, or innocuous endometrial changes such as a pseudodecidual pattern. No case of malignancy was encountered in any patient in this study. The present study suggests that continuous combined hormone replacement therapy appears to be safe with regard to endometrial health. In the majority of women an inactive endometrium or non-assessable biopsy result will be encountered. However, the numbers examined here are small and endometrial carcinoma has been reported to occur. Continuing follow-up of patients on continuous combined HRT is therefore essential.

Isoflurane for removal of chest drains after cardiac surgery.

Thirty-five patients who had undergone uncomplicated cardiac surgery were randomly allocated to receive either Entonox or isoflurane 0.25% in Entonox as inhalational analgesia for the removal of their two chest drains. The gases were presented premixed in high-pressure cylinders and were self-administered by means of a demand valve. The removal of the second drain was more painful than the first but that pain was better controlled by isoflurane 0.25% in Entonox than by Entonox alone.

Case report: radiological features of epidermal inclusion cyst of the tympanic membrane.

Computed tomography (CT) proved to be invaluable in diagnosing and ascertaining the extent of an epidermal inclusion cyst of the tympanic membrane secondary to a previous myringoplasty.

Intravenous pamidronate in the treatment of osteoporosis associated with corticosteroid dependent lung disease: an open pilot study.

BACKGROUND: Bisphosphonates have been shown to be effective agents in the treatment of postmenopausal osteoporosis. Because corticosteroid associated osteoporosis is often associated with increased bone turnover, the effect of intermittent intravenous infusions of pamidronate on this condition has been investigated. METHODS: Seventeen patients (five male) with chronic corticosteroid dependent lung disease (15 asthma, two sarcoidosis) were treated with infusions of 30 mg pamidronate once every three months for one year. These patients had been taking an average of 14 (range 7.5-40) mg prednisolone a day for an average of 14 (range 3-30) years. Bone density measurements, by dual energy x ray absorptiometry, and radiography of the dorsolumbar spine were carried out before and one year after treatment. Bone formation was assessed by measurement of serum alkaline phosphatase and bone resorption by measurement of the fasting urinary hydroxyproline: creatinine ratio at the same time as densitometry and radiography were performed. RESULTS: Pretreatment density of L2-4 and the neck of the femur was significantly lower in these patients compared with a cohort of 100 age and sex matched controls (L2-4 (mean (SEM)): 0.906 (0.050) g/cm2 v 1.142 (0.016) g/cm2; neck of femur: 0.793 (0.030) g/cm2 v 0.936 (0.013)) g/cm2. After treatment there was a significant fall in serum alkaline phosphatase activity from (mean (SEM)) 220 (16) U/1 to 174 (9) U/1 (normal 80-280 U/1) and in the fasting urinary hydroxyproline:creatinine ratio from (mean (SEM) 0.040 (0.006) to 0.024 (0.003) (normal < 0.033). A significant rise was noted in L2-4 density to 0.927 (0.047) g/cm2; mean rise of 3.4%). No change was noted in density of the neck of the femur. CONCLUSIONS: Intermittent infusions of intravenous pamidronate would seem to be effective in both reducing turnover of bone and increasing bone density in corticosteroid induced osteoporosis associated with chronic lung disease. Longer term controlled studies are indicated.

A comparison of the pharmacodynamics of rocuronium and vecuronium during halothane anaesthesia.

Thirty healthy patients were randomised to receive either a single bolus dose of rocuronium 0.6 mg.kg-1 or vecuronium 0.1 mg.kg-1 during halothane anaesthesia. Onset time, duration 25, duration 75 and train-of-four 70 were measured. The onset of neuromuscular blockade following rocuronium was more rapid than vecuronium (p = 0.0001). All other pharmacodynamic parameters were similar. During the first minute following injection of the neuromuscular blocking agent, the heart rate increased by 36% in the rocuronium group but remained stable in those patients who received vecuronium (p = 0.0008). No adverse effects were noted in either group.

Real time ultrasound in the assessment of intraocular foreign bodies.

The accurate detection and localisation of retained intraocular foreign bodies (IOFB) is important in the planning of subsequent surgical management. Using a porcine eye model, the authors have compared the relative detection rates of real time ultrasonography and plain roentgenograms for a variety of IOFBs. With an overall detection rate of 93%, ultrasonography appears to be a considerably more sensitive investigative tool than plain roentgenograms (40%) for the imaging of IOFBs, particularly those that are non-metallic.

Bispecific F(ab' gamma)2 antibody for the delivery of saporin in the treatment of lymphoma.

This work describes the successful use of bispecific F(ab' gamma)2 antibody (Ab) in combination with a ribosome-inactivating protein (RIP), saporin, for the treatment of neoplastic disease in vivo. A total of three thioether-linked F(ab' gamma)2 heterodimers were prepared, each having dual specificities for saporin and the guinea pig lymphoblastic leukemia, L2C. In all three cases specificity for the L2C cells was provided by a high affinity mouse anti-idiotype (anti-Id) mAb, whereas the antisaporin activity came from either one of two mouse mAb or an affinity-purified rabbit polyclonal Ab. In vitro studies, measuring protein synthesis, showed that all three derivatives were extremely efficient at delivering saporin to L2C cells, to the extent that addition of the rabbit Fab' gamma-containing bispecific Ab to cell culture at 1 microgram/ml increased the toxicity of saporin (50% inhibiting concentration) by close to 90,000-fold. Similarly, in leukemic guinea pigs, a small dose of saporin (10 micrograms) which by itself showed no therapeutic effect, was able to completely eradicate Id-positive tumor when given in combination with an excess of bispecific Ab. Although tumors did eventually emerge in most of these animals, immunofluorescence analysis showed that in almost all instances the escaping cells were Id- variants of the L2C. Experiments to define the optimal treatment regimen in this model showed that, although the administration of saporin and bispecific Ab at separate sites could be therapeutically effective, mixing the Ab and saporin to form immune complexes before injection did generally enhance their performance. A molar surplus of bispecific Ab in these mixtures both extended the metabolic survival of the saporin and enhanced the therapeutic performance, with molar ratios above 3:1 generally being required for optimum treatment when using saporin at 10 micrograms. Derivatives containing polyclonal antisaporin were more efficient than those containing mAb, yielding optimum therapeutic results with a molar ratio of 1.5:1 when combined with 10 micrograms saporin. These findings have shown that bispecific F(ab' gamma)2 Ab, as well as being straightforward to prepare, can also function as an extremely efficient vector for delivering cytotoxic agents such as ribosome-inactivating protein to unwanted cells in vivo.