Enhanced recovery after fetal spina bifida surgery: what is our global practice?

OBJECTIVE: Prenatal spina bifida closure results in improved outcomes for the child compared to postnatal surgery but is associated with significant maternal morbidity. Optimization of the perioperative care for women who underwent fetal spina bifida surgery could improve maternal and pregnancy outcomes. Enhanced Recovery After Surgery (ERAS) protocols are multimodal, evidence-based care plans that have been adopted for multiple surgical procedures to promote faster and better patient recovery and shorter hospitalization. This study aims to explore if fetal centers have implemented ERAS principles in this setting. Furthermore, we provide recommendations for the perioperative management of patients undergoing fetal spina bifida surgery. METHODS: Fifty-three fetal therapy centers offering prenatal surgery for open spina bifida were identified and invited to complete a digital questionnaire covering their pre-, intra- and postoperative management. An overall score was calculated per center based on the center's compliance with 20 key ERAS principles, extrapolated from ERAS guidelines for cesarean section, gynecologic oncology and colorectal surgery. Each item was scored 1 or 0 when the center did or did not comply with each principle, with a maximum score of 20. RESULTS: The questionnaire was completed by 46 centers in 17 countries (response rate 87%). Twenty-two centers (48%) exclusively perform open fetal surgery (laparotomy and hysterotomy), whereas 14 (30%) offer both open and fetoscopic procedures and 10 (22%) use fetoscopy only. The perioperative management of patients undergoing fetoscopic and open surgery was highly similar. The median ERAS score was 12 (mean 12.5, SD 2.4, range 8-17). Center compliance was the highest for the use of regional anesthesia (98%), avoidance of bowel preparation (96%), and thromboprophylaxis (96%), while the lowest compliance was achieved for preoperative carbohydrate loading (15%), postoperative nausea and vomiting prevention (33%), avoidance of overnight fasting (33%) and a 2-hour fasting period for clear fluids (20%). ERAS scores were similar in centers with a short (2-5 days), medium (6-10 days) and long (≥11 days) hospital stay (12.8 ± 2.4, 12.1 ± 2.0, and 10.3 ± 3.2, respectively, p=0.15). Furthermore, there was no significant association between ERAS score and surgical technique or center volume. CONCLUSION: The perioperative management of fetal spina bifida surgery is highly variable across fetal therapy centers worldwide. Standardizing protocols according to ERAS principles may improve patient recovery, reduce maternal morbidity, and shorten hospital stay after fetal spina bifida surgery. This article is protected by copyright. All rights reserved.

Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.

Morquio A (Mucopolysaccharidosis IVA; MPS IVA) is an autosomal recessive lysosomal storage disorder caused by partial or total deficiency of the enzyme galactosamine-6-sulfate sulfatase (GALNS; also known as N-acetylgalactosamine-6-sulfate sulfatase) encoded by the GALNS gene. Patients who inherit two mutated GALNS gene alleles have a decreased ability to degrade the glycosaminoglycans (GAGs) keratan sulfate and chondroitin 6-sulfate, thereby causing GAG accumulation within lysosomes and consequently pleiotropic disease. GALNS mutations occur throughout the gene and many mutations are identified only in single patients or families, causing difficulties both in mutation detection and interpretation. In this study, molecular analysis of 163 patients with Morquio A identified 99 unique mutations in the GALNS gene believed to negatively impact GALNS protein function, of which 39 are previously unpublished, together with 26 single-nucleotide polymorphisms. Recommendations for the molecular testing of patients, clear reporting of sequence findings, and interpretation of sequencing data are provided.

A randomised, double-blind, placebo-controlled trial of a recombinant version of human alpha-fetoprotein (MM-093) in patients with active rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) tends to remit during pregnancy, with more patients achieving remission in the third trimester, coinciding with an increase in levels of alpha-fetoprotein (AFP). In vitro and animal studies have shown that AFP has immunomodulatory properties. MM-093 is a non-glycosylated, recombinant version of human AFP. OBJECTIVE: To assess the safety, tolerability and clinical effects of MM-093 during a 12-week, randomised, double-blind, placebo-controlled study. METHODS: 12 patients with RA, who had active disease and were on stable doses of methotrexate, received weekly subcutaneous injections of placebo or 21 mg of MM-093. Assessments were carried out at baseline and weekly thereafter. RESULTS: Baseline characteristics were similar in both groups. There was one dropout in the placebo group, due to flare of disease. Treatment with MM-093 was well tolerated. No serious adverse event was observed. By day 85, MM-093 produced a significant mean improvement from baseline in Disease Activity Score 28 (DAS28; 0.913 vs 0.008, p = 0.033) and patient's global assessment (28.9% vs -36.3%, p = 0.02) compared with placebo. CONCLUSION: This is the first randomised, controlled trial of MM-093, a recombinant version of human AFP, in patients with RA. MM-093 was well tolerated. Evidence of efficacy was observed, suggesting that MM-093 may have therapeutic potential in RA.

Fatigue in rheumatoid arthritis reflects pain, not disease activity.

OBJECTIVE: We determined the amount of fatigue experienced by patients with RA, and its relationship to synovitis, pain and other common clinical features. We also examined to what extent RA fatigue is improved by disease-modifying antirheumatic drugs (DMARDs) and anti-tumour necrosis factor (TNF) therapy. METHODS: We studied two cohorts of 238 and 274 RA patients cross-sectionally and examined treatment responses in 30 RA patients starting anti-TNF and 54 starting DMARDs followed for 3 and 6 months. We measured fatigue using visual analogue scores (VAS) and Medical Outcomes Study Short Form 36 (SF-36) vitality scores. We recorded the disease activity score for 28 joints and its components (tender/swollen joint counts, patient global assessment, ESR), morning stiffness, health assessment questionnaire, physician global assessment, erosive disease, nodules, rheumatoid factor, concomitant medications and illnesses, and the SF-36 questionnaire. RESULTS: Fatigue was common in RA patients; over 80% had clinically relevant fatigue (VAS > or =20 mm), over 50% had high levels (VAS > or =50 mm). It was associated with pain and changes in mental health, particularly depression. In each of the two cross-sectional cohorts, this relationship was similar whichever measures of fatigue and mental health were used. Fatigue fell with DMARDs and anti-TNF: before treatment, 87% of patients had high fatigue, after treatment this fell to 50%. These treatment effects were mainly linked to improvements in pain. CONCLUSIONS: High fatigue levels characterize RA and are mainly linked to pain and depression. The association with disease activity is secondary. Fatigue falls with DMARD and anti-TNF therapy. The balance of evidence suggests that fatigue is centrally mediated in established RA.

The consequences of rheumatoid arthritis: quality of life measures in the individual patient.

Despite conventional treatment, RA still has many deleterious consequences. From the patients' perspective, these include persistent pain, functional disability, fatigue, and depression modified by health beliefs and underlying psychological problems. Disability is a consequence of pain, active synovitis and joint damage. It is usually assessed by self-reported questionnaire; the Health Assessment Questionnaire (HAQ) remains the dominant disability measure, although generic health measures such as Short Form-36 and Nottingham Health Profile provide similar information. Treatment with disease modifying drugs and biologic agents improves pain, fatigue and disability. We specifically evaluated the effects of both these drugs and also disease duration on disability assessed by HAQ scores, as there is most information on this topic and it is of fundamental importance to patients. In early RA HAQ gives a 'J-shaped' curve; the initial fall is due to the immediate benefits of treatment and the subsequent gradual rise due to the inability of therapy to fully suppress the disease or prevent progressive joint damage. In established RA HAQ scores increase by about 1% annually and over 25 years average HAQ scores increase by 1.0. Disease modifying drugs and biologics both significantly reduce HAQ scores and the reduction is maintained for 2-5 years. This reduction is seen in both early and established disease. Early steroid therapy has immediate symptomatic treatment, but does not have long-term benefits. Over 5 years the impact of aggressive therapy with disease modifying drugs declines and there is evidence that insufficient treatment is given to many patients with RA. The outcome of RA is greatly improved by current treatment with disease modifying drugs and biologic agents. However, more needs to be done and achieving better results is enhanced by routinely measuring the impact of the disease in routine practice.

Depo provera discussion paper on clinical care, effectiveness and side effects

Recent changes to the health services have led to an increased provision of clinical care in family planning clinics. While some women may only require contraceptive services, others may demand advice on a breadth of lifestyle issues, including diet and nutrition. Obesity affects 17% of women of childbearing age in Scotland and being overweight during pregnancy has significant health risks. A postal survey of 227 nurses identified as working in family planning clinics in Scotland was conducted in 1998. After a mail shot and one reminder, a net response rate of 64% (n = 145) was achieved. Overall, it was found that obesity was perceived as the most extensive problem in women of childbearing age. Seventy nurses (48%) reported that, in addition to offering family planning services, they gave dietary advice 'frequently' or 'always' to their clients without being asked. There were differences in nutrition-related activities in consultations between nurses offering family planning services only and those who routinely offered nutritional advice. Over half (61%) of the nurses reported that they would give advice regarding weight management even if the patients were not seeking help, although there was no significant difference between the two comparison groups. In some cases, the nutritional advice offered to clients highlighted a deficit in training. Most nutrition education came from diploma and/or training courses and scientific literature, followed by 'experience'. Those nurses already embracing a nutritional advice and guidance role were more interested in further nutrition training (p = 0.018) than the other nurses. However, overall, 67% of the nurses wished to train further in nutrition and weight management. The findings suggest that family planning nurses should be supported to develop nutritional advice and guidance skills, and that there is a pressing need for training in public health nutrition and weight management for nurses working in family planning services.

Tolerability and reasons for discontinuation of Norplant in an inner city population.

We carried out a retrospective analysis of the continuation rates of 142 Norplant acceptors. Follow-up data was available on 110. We assessed the relative impact of side effects on discontinuation. No serious complications (immediate or late) were observed during the 3-year study period and no pregnancies occurred. The 3-year continuation rate was 88%. The commonest reported side effect was cycle disruption (64% of users). However this only accounted for 31% of discontinuations. This we attribute to thorough counselling about menstrual disruption. On the other hand androgenic side effects accounted for 12% of discontinuations but were experienced by 10% of users-perhaps because some users did not expect them. We conclude that Norplant is highly acceptable when offered with specialist counselling and support. Non-bleeding side effects accounted for relatively higher discontinuations and may need to be emphasised in counselling. A dedicated service enhanced acceptability.

Depo Provera. Position paper on clinical use, effectiveness and side effects.

Depo Provera (medroxyprogesterone acetate, DMPA) when given as 150 mg by deep intramuscular injection every 12 calendar weeks (84 days+5 days), is a highly effective contraceptive with a very low failure rate comparable to modern copper IUDs and lower than many other methods. It should be available as a first line method to all who wish to make an informed choice about reversible methods of contraception. Pre-use counselling is essential to minimise the effect of menstrual change which occurs in most patients. However there is great patient variability. Use of DMPA is independent of intercourse and also independent of the user's memory (and thus of continuing motivation), other than remembering the 12 weekly appointments. For many women this is a great advantage. Oral contraceptive methods involve remembering to take a pill each day, in the case of the progestogen only pill within the same three hours each day. This places considerable strain on women who lead irregular lifestyles, who are very busy or travel frequently. Such women often describe a constant 'fear of forgetting', especially with the POP. The main potential disadvantage of DMPA in this country are likely to be menstrual disturbance and weight gain. The combined oral contraceptive pill gives the appearance of excellent cycle control because it removes the natural cycle altogether and replaces it with an artificial one. All progestogen-only methods, whether low or high dose, lead to menstrual disturbances, so in this respect DMPA is not unique. Although troublesome, the menstrual disturbances which occur in DMPA users very rarely require operative medical intervention, and can often be improved simply by short courses of oestrogen or shorter injection intervals. Again, women need to know what can be done so that they are aware that they should seek advice early, rather than miserably waiting.for their 12 week appointment. DMPA has no appreciable effects on blood pressure or thrombosis risk. In this it has an advantage over the combined oral contraceptive pill, and provides a simple, effective alternative for women who cannot use the pill for these reasons. Similarly, it has been suggested that women who suffer from focal migraine and are therefore advised against use of the combined oral contraceptive pill can still use progestogen-only contraceptives. Although the POP is medically safe in these circumstances, in young women it is less effective, and involves strict time keeping, which will be disadvantageous for some women. Side effects, long term use and schedules of administration are also discussed. The use of local protocols to allow nurse administration is to be supported both in general practice and the clinic situation. Perhaps the most important issue surrounding the use of DMPA is that of patient information. The method has had a particularly bad public image, which naturally makes potential users anxious and subject to misinformation from poorly informed or biased sources. Also, it is temporarily irreversible during its three months duration, so the duration of any problems or anxieties resulting from side effects may be longer than for other methods. It is of paramount importance that easily understood, accurate patient information leaflets are available, since biased and inaccurate information is readily available from women's magazines, perpetuating the myths surrounding the method.

PIP: This study presents a review of current clinical evidence on the usefulness of Depo Provera (medroxyprogesterone acetate, DMPA), a long-term method of reversible contraception. It is taken as an intramuscular long-acting agent (150 mg every 12 calendar weeks). The user failure rate approaches the method failure rate, which varies considerably with age. In terms of metabolic effects, it did not show changes in cholesterol or triglycerides and had no significant effect on hemostasis, which impairs the oral glucose tolerance test (OGTT) glucose response and increases insulin response. There were no significant adverse effects on long term growth and development in DMPA exposed children and no delays in return to fertility. For cancers, controlled surveillance of DMPA users found no overall increased risk of ovarian, liver or cervical cancer and even found a prolonged protective effect in reducing the risk of endometrial cancer. However, increased risk of breast cancer in recent users was observed; this could be due to enhanced detection of breast tumors of women using DMPA. The main DMPA disadvantages are menstrual disturbance and weight gain after 1 year. Bone mineral density (BMD) is found to be significantly lower. DMPA patients' sociodemographic characteristics and behavior placed then at higher risk for adverse pregnancy outcome in low infant birth weight and also possibly in polysyndactyl and chromosomal defects. Thus, for injectable progestogen, the data is again less conclusive. Risks may be similar to POP (progestogen-only contraceptive pill), but did not reach significance in the meta-analysis.

Reducing missed opportunities for immunizations. Easier said than done.

BACKGROUND: Missed opportunities for immunizations are associated with underimmunization of preschool-age children. Practice policies limiting immunizations to scheduled preventive visits and guidelines requiring legal guardians to sign consent forms for vaccinations are 2 factors contributing to missed opportunities. However, methods to change these policies have not been sufficiently evaluated. OBJECTIVE: To measure the effectiveness of (1) changing practice policies to incorporate the new national standard to screen and vaccinate eligible children at all office visits and (2) eliminating legal guardian signature requirements. DESIGN: A randomized controlled trial of 2 interventions: (1) changing practice policy and routine to have office nurses screen for immunization status at all visits, attach immunization reminder cards to medical charts for eligible patients, and have providers vaccinate eligible children ("no missed opportunities" intervention) and (2) changing practice guidelines to allow vaccinations without a legal guardian's signature. The first intervention was performed at both sites; the second only at the neighborhood health center (NHC). SETTING: A Pediatric Continuity Clinic in a teaching hospital (hereafter referred to as Clinic), and an NHC. PATIENTS: Enrolled in the trial were 1005 Clinic patients and 983 NHC patients, 0 to 2 years of age. MAIN OUTCOME MEASURES: Missed opportunity rates, immunization rates, and rates of preventive services. RESULTS: Eliminating the requirement for a legal guardian's signature had no effect on any of the outcome measures. The no missed opportunities intervention was partially effective. Study patients had slightly fewer missed opportunities than control patients at each site: (0.60 vs 0.90 per patient per year at the Clinic, P = .01; 1.1 vs 1.3 per patient per year at the NHC, P = .02). For study group patients, immunization reminder cards were attached to medical charts in only one third of vaccine-eligible visits; when attached, they markedly increased vaccination by providers (odds ratio for vaccinating at a visit was 6.9 comparing visits when immunization reminder cards were attached vs not attached). However, at the end of the study, immunization rates were similar for study and control groups at each site. The number of undervaccinated days was slightly lower for the no missed opportunities study group at the Clinic than for the control group (56 days vs 77 days, P < .001), but they were similar for both groups at the NHC. There were no differences in rates of preventive visits or screening tests between study and control groups. CONCLUSIONS: The interventions evaluated to reduce missed opportunities did not increase immunization rates. The key problem was failure to screen for immunization status at all visits. More effective interventions will be needed to overcome barriers within busy primary care practices to substantially reduce missed opportunities.

Selective vagal rhizotomies: a new dorsal surgical approach used for intestinal deafferentations.

We have developed a dorsal intracranial surgery that is minimally invasive and gives excellent access to either afferent or efferent vagal rootlets to produce selective deafferentations or deefferentations in the rat. We have combined this new unilateral afferent rhizotomy with a contralateral celiac branch cut (to completely deafferent the intestines) and a duodenal catheter placement 4 cm distal to the pylorus. Animals were maintained with 17 h/day access to a nutritionally complete liquid diet. Measures of first meal size, daily intake, and body weight before and after both surgeries indicated that animals with unilateral vagal deafferentiations recovered as fast and completely as sham-operated controls. Intraduodenal oleate (1.2 kcal) infusions reduced the size of the first meal in surgical controls (by 64%; P < 0.01) but not in the deafferented rats. A dual wheat germ agglutinin-horseradish peroxidase/Fluorogold protocol provides verification of sensory and motor lesions. The selective vagal deafferentation provided by the new surgery offers a useful model for determining gastrointestinal sites of nutrient detection and separating pre- and postabsorptive consequences of a meal.

Male postpubertal facial growth in Class II malocclusions.

Maxillary and mandibular postpubertal growth changes were assessed from lateral cephalograms taken when subjects were 16 and 20 years of age. The sample consisted of 39 male subjects with no previous orthodontic treatment who exhibited Class II skeletal characteristics. Significant increases in mean maxillary and mandibular measurements were observed over the age period studied. Mean mandibular growth (Co-Gn) was approximately three times that of maxillary growth (Co-A). Total mandibular growth observed between 16 to 20 years of age was approximately 4.3 mm. The mandible appeared to rotate anteriorly superiorly, reflected by a mean reduction in mandibular plane angle of 1.47 degrees and a greater increase in posterior versus anterior face height. There were not statistically significant changes in incisor angulation. Mean growth changes in this Class II sample were comparable to those previously reported for male subjects with Class I malocclusions over the same age period, suggesting a similarity in postpubertal development between these two groups.

Sequence-dependent activity of 5-fluorouracil plus tauromustine in a transplantable well-differentiated murine colon adenocarcinoma.

Previous in vitro studies with 5-Fluorouracil (5-FU) plus Tauromustine (TCNU) demonstrated sequence-dependent effects. This study extended these investigations into an in vivo experimental model, relevant to clinical disease. A transplantable murine adenocarcinoma of the colon, MAC 29, was shown to have stable histology and reproducible growth. This model was used to determine the influence of sequence of administration of this drug combination. Effects ranged from antagonism, with 5-FU given 24 hours before TCNU, to addition, simultaneous treatment, and synergism, 5-FU 24 hours after TCNU. Careful consideration of sequence should be made during the evaluation of this combination in clinical trials.

Monoclonal antibody study of the decorated spongiome of contractile vacuole complexes of Paramecium.

A monoclonal antibody (mAb) has been developed and selected by immunofluorescence for the radial canals of the contractile vacuole complex (CVC) of Paramecium multimicronucleatum. By applying indirect immunogold labeling to thin frozen sections this mAb has been shown at the electron microscopic level to be specific for the decorated spongiome. We have used the mAb to study the normal interfission appearance as well as developmental stages of the decorated spongiomes. Two decorated spongiomes, presumably involved in water sequestration, radiate as 5-10 bands from unlabeled, circular, 25 microns diameter centers. Two new CVCs arise just anterior to the space occupied by the old spongiomes, the new anterior CVC appearing slightly before the posterior one. Development of the new spongiomes around a 10 microns unlabeled central zone is accompanied by a regression of old spongiome bands until the lengths of these bands in both old and new CVCs are equal just before cell division. After division both old and new spongiome bands grow at equal rates to the same length. Exceptions to the above general scheme, both in number of CVCs in interfission, as well as in position of the new relative to the old CVCs, are also observed.

Substance P and bombesin elevate cytosolic Ca2+ by different molecular mechanisms in a rat pancreatic acinar cell line.

1. Dual-excitation microfluorometry (Fura-2 as indicator) was employed to monitor directly changes in the cytosolic calcium concentration [( Ca2+]i) in single cells. We investigated and compared the effects of stimulation of AR42J rat pancreatic acinar cells by two peptide agonists, substance P and bombesin. 2. Substance P (10(-7) M) and bombesin (10(-8) M) each gave rise to a marked, but transient, elevation in [Ca2+]i. The calcium signals evoked by the two peptides were qualitatively and quantitatively very similar. However, in the absence of extracellular Ca2+ the response to substance P, but not bombesin, was abolished. These results suggest that substance P induces calcium influx across the cell surface membrane but does not release calcium from internal stores. Bombesin in marked contrast releases calcium from intracellular stores in the absence of any detectable calcium influx. 3. Depolarization by high-K+ extracellular solutions evoked a marked, but transient, rise in [Ca2+]i. This elevation in [Ca2+]i was strictly dependent upon the presence of Ca2+ in extracellular media. 4. Nifedipine (5 x 10(-6) M), an antagonist of L-type voltage-dependent Ca2+ channels, blocked the elevations in [Ca2+]i induced by either substance P or high-K+ solutions, but not that evoked by application of bombesin. 5. Patch-clamp, single-channel current recordings from cell-attached patches of membrane confirmed the presence of voltage-dependent calcium channels in the surface membranes of AR42J cells. Whole-cell current recordings demonstrated voltage-dependent inward Ca2+ (Ba2+) currents which were increased in amplitude by substance P and blocked by nifedipine. 6. The protein kinase C (PKC) activators, the phorbol diester, phorbol 1,2-myristate 13-acetate (PMA, 10(-7) M), and cell-permeable diacylglycerol analogues, 1-oleoyl-2-acetyl-sn-glycerol (OAG, 2.5 x 10(-6) M) and sn-2-dioctanoyl glycerol (DiC8, 2.5 x 10(-6) M), mimicked the effect of substance P, but not bombesin, in elevating [Ca2+]i in a manner that was blocked by removal of extracellular Ca2+ or application of nifedipine. 7. The PKC inhibitor, polymyxin B (2.5 x 10(-6) M), applied 2 min prior to stimulation blocked the effects of substance P and PKC activators, but not bombesin, in elevating [Ca2+]i. 8. The calcium signals evoked by substance P and bombesin are achieved by activation of different molecular mechanisms. Substance P, the evidence suggests, activates PKC which in turn stimulates calcium influx by opening voltage-dependent Ca2+ channels in the cell surface membranes.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium metabolism in malaria-infected erythrocytes.

Changes in the concentration of free calcium regulate many intracellular metabolic pathways and other important aspects of cellular function. The erythrocyte maintains intracellular calcium concentrations within a narrow range, but infection by malarial parasites disrupts these homeostatic mechanisms. The observation that infected erythrocytes have supranormal concentrations of calcium raises questions about the storage and functions of calcium ions within parasites. These are addressed in the following review by Sanjeev Krishna and Laura Squire-Pollard.

Pathovar-Specific Antigens of Xanthomonas campestris pv. begoniae and X. campestris pv. pelargonii Detected with Monoclonal Antibodies.

Two monoclonal antibodies specific for lipopolysaccharide antigens of Xanthomonas campestris pv. begoniae and pv. pelargonii reacted with all of their respective pathovar strains and not with 130 strains of other xanthomonads or 89 nonxanthomonads tested. These results, as well as previous results, indicate that pathovar-specific monoclonal antibodies were readily generated to strains of X. campestris pathovars that generally infect single hosts.

The establishment, characterization and calibration of human ovarian carcinoma xenografts for the evaluation of novel platinum anticancer drugs.

Twenty-three serially transplantable ovarian carcinoma xenografts have been established in female nude mice from forty-two donor samples provided by both previously treated and untreated patients. The lines are all of human karyotype and mirror the histopathology of the original explant. Sixteen examples have been calibrated against four reference platinum drugs: cisplatin, carboplatin, iproplatin, tetraplatin. Three distinct patterns of response were observed: (i) tumours which were comparably sensitive to all four drugs (2 lines); (ii) tumours which were comparably refractory to treatment with all four drugs (5 lines); (iii) tumours which exhibited "individual" patterns of response to the group of calibrating drugs (9 lines). The "response rate" overall of the tumour panel to each of the clinically used drugs was 44% (7/16), though the pattern of response was not identical for each drug. Only 2/16 tumours (13%) were sensitive to tetraplatin, these also being the same tumours which were particularly sensitive to the other three drugs. It was also possible to confirm in 8/9 lines that the therapeutic response of the xenograft reflected that of the corresponding patient's tumour to platinum-based chemotherapy. This tumour panel has now been adopted for evaluating novel platinum-based drugs designed specifically for the treatment of ovarian cancer.

The 5-HT3 antagonist, BRL 43694, does not compromise the efficacy of cisplatin in tumour-bearing mice.

Binary combinations of cisplatin and the 5-HT3 antagonist, BRL 43694, have been used to treat both conventional mice bearing either L1210 leukaemia or ADJ/PC6 plasmacytoma and nude mice xenografted with a human ovarian carcinoma (HX/110). In no case was there evidence for antagonism by the antiemetic of the antitumour properties of cisplatin.