Ethnic differences in the levator hiatus and pelvic organ descent: a prospective observational study.

OBJECTIVE: To date, most studies on functional anatomy of the pelvic floor have focused on Caucasian women. There is scant information on this topic involving other ethnic groups. The aim of this study was to investigate levator hiatal area and pelvic organ descent in three racially diverse ethnic groups of healthy nulliparous South Asian, Caucasian and black South African women, using three/four-dimensional (3D/4D) transperineal ultrasound (TPS). METHODS: Nulliparous women aged 18-40 years from three different ethnic groups were recruited for this prospective observational study between June 2012 and April 2015. After informed consent and clinical examination of the pelvic floor, all patients underwent a 3D/4D-TPS examination. Ultrasound volumes were captured at rest, on maximum pelvic floor muscle contraction (PFMC) and on maximal Valsalva maneuver. Analyses of variance and covariance were performed to compare the three ethnic groups, and a post-hoc Bonferroni pairwise test was applied. RESULTS: A total of 207 nulliparous women were recruited, comprising 41 South Asian, 69 Caucasian and 97 black women. After controlling for age and body mass index, all measurements of mean levator hiatal area at rest, on PFMC and on Valsalva were higher in black women (all P < 0.0001). Post-hoc Bonferroni pairwise comparison revealed that black women had greater pelvic organ descent and levator hiatal area compared with South Asian and Caucasian women (P < 0.0001). CONCLUSION: This comparative study indicates that there are significant differences in levator hiatal area and pelvic organ mobility between Caucasian, South Asian and black ethnic groups. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Urine cytology as a screening test for bladder infiltration in cervical cancer.

Ultrasound is currently used as a screening test for bladder infiltration in patients with advanced-stage cervical cancer at our institution. Cystoscopy is reserved for patients with abnormal bladder ultrasound findings. This study was undertaken to reevaluate this policy and to compare the results of different screening tests. The study was carried out in Pretoria academic complex. All newly diagnosed cervical carcinoma patients stage II and above were included in this study. The standard staging investigations were done on all patients. In addition, urine midstream and catheter specimens were sent for cytology. Cystoscopy and biopsy were performed on all patients. Two hundred twenty-eight patients were enrolled into this study. At cystoscopy, 47 patients had bladder mucosa suspicious of malignant infiltration, of which 17 had bladder mucosa infiltration diagnosed on histology. Urine catheter cytology has a sensitivity of 94% and specificity of 82% for bladder mucosa infiltration. The predictive value of a positive test is 31% and for a negative test is 99%. Catheter urine cytology is a very useful screening test for bladder infiltration in patients with cervical cancer. Cystoscopy should be reserved for patients with abnormal urine cytology in resource-poor settings with a large burden of disease.

Medical students' perceptions of their development of `soft skills' Part I : A qualitative research methodology

Background: Following the introduction of a new; integrated; problem-oriented undergraduate medical curriculum at the University of Pretoria (UP) in 1997; a research project was undertaken to study interpersonal skills; professional attitudes; teamwork; ethics and related topics - which have come to be known collectively as `soft skills'. This contribution is the first of two articles on the professional socialisation of medical students and their development of `soft skills'. It describes the particular qualitative methodology developed for; and applied to; the study of soft skills among medical students at UP. Methods: This paper describes the aim of the study; reasons for adopting a qualitative research approach to achieve this aim; the theoretical orientation underpinning the qualitative approach that we considered most suitable; the design; the sampling; the data management and analysis; and the methods that we deployed to ensure the credibility of the findings. Research Design: The aim of the study was to explore the subjective meanings that students attributed to soft skills; as they understood them. These subjective meanings involve the way students interact meaningfully with fellow students; lecturers and other individuals participating in the medical and clinical education programme; and the way they construct shared conceptualisations of soft skills and medical education in their lives and social world. A qualitative approach was considered most appropriate; as this study set out to uncover subjective and diverse meanings that do not necessarily amount to generalisable truths. The particular qualitative strategy or design used was that of an extended case study; or `casing'; within the modernist theoretical orientation of symbolic interactionism. Elements of process evaluation were incorporated into the design to account for the process of curriculum reform within which this study was embedded.We recruited participants for this study from two cohorts of students. The first group; who completed their studies in 2001; had followed the traditional curriculum; while the second group; who completed their programme in 2002; had followed the reformed curriculum. The data collection tools were face-to-face individual interviews; focused group interviews and solicited autobiographical sketches. The utilisation of more than one method or data source enabled triangulation or cross-checking of findings. We followed an inductive reasoning approach; which means that we did not search for data to test any hypotheses that had been formulated prior to commencing the study; but focused instead on building constructs that were grounded in or reflected intimate familiarity with the students' world. Conclusion:The modernist qualitative research approach enabled us to uncover; describe and illuminate the subjective points of view on soft skills as expressed by final-year medical students before and after curriculum reform. More specifically; by carrying out an extended case study we were able to perform a process evaluation of the curriculum reform in terms of soft skills and the professional socialisation of the students. This paper outlines how qualitative research methods enabled us to capture and explore aspects of the inner life (social worlds) of these students. Whether they would be the same; similar or different in another setting are questions for further exploration or research - questions prompted by our study in a manner that illuminates the qualities that may be inherent in these subjective meanings

Medical students' perceptions of their development of 'soft skills' Part II: the development of 'soft skills' through 'guiding and growing'

Background: This paper reports on medical students' views on the ways in which their `soft skills' were developed. It is the result of a study on soft skills among two groups of students before and after curriculum reform at the School of Medicine of the University of Pretoria. One of the aims of the reform was to provide more teaching and learning opportunities for the development of soft skills. Soft skills include professional interpersonal and social skills; communication skills; and professional and ethical attitudes.Methods: As symbolic interactionism was used as the theoretical framework to guide the research; qualitative methods were used to collect the data. A purposive-theoretical sample of 42 final-year medical students from the traditional curriculum and 49 from the reformed curriculum was recruited. Data were collected by means of focus groups; individual in-depth interviews and autobiographical sketches.ResultsThe same categories of comments emerged from the data collected from the study participants from both the traditional and the reformed curriculum. The students ascribed their behaviour related to soft skills to personality and innate features. They had varying opinions on whether soft skills could be taught; but there was as a strong feeling that teaching should focus on principles and guidelines for dealing with difficult situations. They believed that; in the end; they should take responsibility for their own development of soft skills. Most participants felt they could at least grow through exposure to teaching activities and the observation of role models. They also indicated that they had developed their soft skills and constructed their own identity through their interaction with others. Their definition of situations was shaped by their interactions with doctors and educators; fellow students and other health professionals. Interaction with patients was considered the most important. For both groups of students their third year was a watershed; as it is the first year of more intensive patient contact and the beginning of serious learning from interaction with patients. The views on the development of soft skills differed very little between the traditional and reformed curriculum groups; except that students who had followed the reformed curriculum felt more prepared through the increased teaching and training efforts. Further consideration needs to be given to the intention of the changed curriculum compared to the actual effect.The way in which the participants in the study described their development of soft skills could be categorised as a complex interplay between `being' and `becoming'. Instead of using the word `acquisition' of soft skills; `development' seemed to be more appropriate. The metaphor of `guiding' and `growing' also captures the development of these skills better than the terms `teaching' and `learning'. Conclusion: Teaching activities in the clinical years should be adapted with a view to facilitating the students' professional growth. New models for the development of medical educators should be created and institutional barriers should be investigated

Management of cervical premalignant lesions.

Management of cervical preneoplasia starts with an abnormal smear result. The use of the Bethesda system is recommended. The management of patients with low-grade abnormal smear results varies around the world. Patients with atypical squamous cells on cytology are recommended to be subclassified into atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells where high-grade squamous intra-epithelial lesions (HSIL) cannot be excluded (ASCH) groups. While patients with ASCUS can be followed with cytology or colposcopy, the risk of having cervical intra-epithelial neoplasia (CIN) is higher in patients with ASCH. Such patients, as well as those with low-grade squamous intra-epithelial lesions on cytology, should be referred for colposcopy to ensure that diagnosis and treatment in CIN is detected. Patients with HSIL should be referred promptly for colposcopic assessment. This should, usually at the same clinic visit, be followed by large loop excision of the transformation zone (LLETZ). Although this is effective treatment, around 15% of patients will have persistent/recurrent disease on cytological follow-up. Patients with positive human papillomavirus DNA tests at follow-up seem to have a considerably higher risk of recurrent preneoplasia than those who have negative tests. Patients over 50 years of age have much higher recurrence risks than younger patients. These factors impact on second-line treatment and follow-up schedules. An important benefit of conservative treatment for CIN with LLETZ is retention of fertility. LLETZ is associated with an increased risk of preterm prelabour rupture of membranes and preterm birth, but not with other adverse pregnancy outcome measures. Conservative excisional management of adenocarcinoma in situ by LLETZ or cold knife cone biopsy is not reported to be as effective as that of CIN, with high risk of residual and recurrent disease at follow-up. Conversely, LLETZ may be acceptable treatment for micro-invasive squamous carcinoma if the excision margins are free of disease and there is no evidence of lymphovascular involvement. The ability to detect and treat premalignant lesions on the cervix reversed the natural history of cervical cancer. Methods of conservative treatment that evolved over decades have been proven safe and effective, allowing retention of fertility. Good clinical guidelines have been developed for most clinical scenarios while some uncertainties persist for other scenarios.

Management of recurrent cervical cancer.

Treatment for cervical cancer is very successful, especially in early stages. However, most patients presenting in late stages of disease will experience recurrence. The prognosis of recurrent disease is very poor and treatment options are limited. The diagnosis of recurrence may be apparent or difficult, but determining the extent of disease is always complex. Routine follow-up of asymptomatic patients has other objectives and is not a reliable way to detect recurrences. Symptomatic patients require extensive investigation to detect the extent of the disease. For patients with central pelvic recurrences, exenteration offers the prospect of survival in more than one-third of cases. Newer developments include laterally extended endopelvic resection that may become an option for patients with more extensive pelvic recurrence. For patients with recurrences of cervical cancer, the roles of second-time radiotherapy or postradiation chemotherapy are very limited. Palliative treatment is important for all patients with untreatable disease. Pain relief forms a central part of palliative care. Caregivers also experience emotional feelings and probably function best in a system offering strong colleageal support.

Tissue banking in South Africa: a 19-year history.

The establishment of a Tissue Bank and the science of Tissue Banking in South Africa started in the 1960s and is still developing. This article describes the development and growth of Tissue Banking in South Africa. The current emphasis is to supply viable bone products that have been produced under the best possible quality controlled circumstances; with the collaboration between different Organ Donation Organisations. Through collaboration, a dramatic increase in the number of donors was noted over the years. Concurrently, there was a dramatic increase in the usage of different allograft products and now necessitates the development of new graft materials for expanding patient options. As an ongoing concern, the Tissue Bank in South Africa experienced an ever increase in costs to enhance quality/safety controls: increase in historical patient information, documentation and serological testing in a population struggling to control HIV. To date, the South African Tissue Bank has not experienced any untoward patient incidence since the 1960s and currently is getting over 500 donors per year.

A possible role of the cytochrome P450c17alpha gene (CYP17) polymorphism in the pathobiology of uterine leiomyomas from black South African women: a pilot study.

BACKGROUND: To investigate the role of the CYP17 gene promoter polymorphism in the pathobiology of uterine leiomyomas in African and Caucasian women. METHODS: During a 6-month period, 145 Caucasian and black South African women undergoing hysterectomy were included prospectively. Blood samples were obtained for DNA analysis. Factors modifying the risk for uterine leiomyoma growth such as age, parity, age at last birth, weight, body mass index, menopausal status, cigarette smoking and oral contraceptive use were determined. RESULTS: The risk for leiomyoma development among black South African homozygous carriers of the CYP17 A2 allele was shown to be significantly increased when compared to women homozygous for the CYP17 A1 allele or to heterozygous women. Logistic regression analysis disclosed age, parity and CYP17 polymorphism to have an impact on the presence of uterine leiomyomas (p-values are, respectively, 0.0006, 0.0001 and 0.03) in black South African women. However, among Caucasian women, logistic regression analysis showed only intake of oral contraceptives to influence the formation of uterine leiomyomas (p = 0.03). CONCLUSION: This exploratory trial suggests that among African women, homozygous carriers of the CYP17 A2 allele expose their myometrium to a stronger estrogenic stimulation contributing to the pathobiology of uterine leiomyomas.

2-methoxyestradiol strongly inhibits human uterine sarcomatous cell growth.

OBJECTIVES: The objective was to test the hypothesis that uterine sarcomatous cells are hormone-sensitive. We included 2-methoxyestradiol, an endogenous metabolite of estradiol with antiproliferative properties. METHODS: Proliferation assays assessed the effects of estradiol, progesterone, tamoxifen, raloxifen, [D-Trp(6)]leuteinizing hormone-releasing hormone (LHRH), ICI 182,780 (faslodex or fulvestrant), and 2-methoxyestradiol on cell growth of a cell line derived from uterine carcinosarcoma, but consisting solely of mesenchymal cells (SK-UT-1). Morphological changes of SK-UT-1 cells after exposure to 2-methoxyestradiol were evaluated and fluorescence immunohistochemistry for tubulin was used to detect changes in the mitotic spindle. Flow cytometry was used to assess the influence of 2-methoxyestradiol on the SK-UT-1 cell cycle as well as the role of p53 in apoptosis. RESULTS: Cell proliferation analysis revealed that SK-UT-1 cells were stimulated by progesterone, tamoxifen, and [D-Trp(6)]LHRH. Cells were insensitive to estradiol, raloxifen, and ICI 182,780. Inhibition occurred after exposure to 2-methoxyestradiol and was accompanied by a threefold increase in the G2/M population, with a concomitant decrease in the G1 population, as shown by cell cycle analysis. SK-UT-1 cells exposed to 2-methoxyestradiol showed morphological changes indicative of apoptosis. Examination of signaling pathways that mediate 2-methoxyestradiol-induced apoptosis showed p53-independent growth inhibition. The inhibition of SK-UT-1 cell growth by arresting the cells during G2/M progression could be attributed to interference with the microtubule system, as determined by fluorescence immunohistochemistry. CONCLUSIONS: The stimulatory effect of progesterone, tamoxifen, and [D-Trp(6)]LHRH suggests that uterine sarcomatous cells are hormone-sensitive. Our finding that 2-methoxyestradiol-mediated growth inhibition of uterine sarcomatous cells occurred in a p53-independent manner may have considerable clinical significance. The inadequate armature against uterine sarcomas and the limited toxicity of 2-methoxyestradiol may render these observations especially important.

Ethnic variations in uterine leiomyoma biology are not caused by differences in myometrial estrogen receptor alpha levels.

OBJECTIVE: Uterine leiomyomas develop in women of reproductive age and regress after menopause, suggesting that they grow in a steroid hormone-dependent fashion. Furthermore, it is widely accepted that symptomatic uterine leiomyomas occur at a twofold to threefold higher frequency in black women than in white women. The present study was designed to investigate a possible physiologic role of racial differences in the myometrial estrogen receptor alpha in this phenomenon. METHODS: We compared the expression of the estrogen receptor and progesterone receptor in myometrium by ligand-binding assay and the estrogen receptor alpha by real-time polymerase chain reaction in women from different ethnic backgrounds who have uterine leiomyoma. RESULTS: Estrogen receptor and progesterone receptor concentrations and estrogen receptor alpha transcription levels were not statistically different between ethnic backgrounds. CONCLUSION: Neither on a transcriptional nor on a protein level were there statistically relevant differences in steroid hormone receptor levels. A causative role for these receptors in the ethnic variation of leiomyoma biology seems unlikely.

PTEN mutations in uterine sarcomas.

OBJECTIVE: Uterinesarcomas comprise three main types: carcinosarcomas, leiomyosarcomas, and endometrial stromal sarcomas. Carcinosarcomas are highly aggressive neoplasms with a biphasic histology of carcinomatous and sarcomatous elements. It is now generally accepted that carcinosarcomas are biphasic tumors that have to be regarded as endometrial carcinomas where metaplasia occurs. Mutations of the PTEN tumor suppressor gene, located on 10q23, play a significant role in the pathogenesis of the endometrioid type of endometrial carcinoma. Loss of heterozygosity of chromosome 10q has been reported in uterine leiomyosarcoma. Since little is known about the molecular pathobiology, our goal was to investigate the potential role of the PTEN gene in the carcinogenesis of uterine sarcomas. METHODS: We examined 21 carcinosarcomas, 21 leiomyosarcomas, and 5 endometrial stromal sarcomas using exon-by-exon polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: Overall 8.5% (4/47) of uterine sarcomas were found to harbor somatic PTEN mutations. Of these, approximately 17% (3/18) were carcinosarcomas with endometrioid-type carcinoma components and approximately 5% (1/21) were leiomyosarcomas. No mutations were detected in carcinosarcomas with nonendometrioid carcinoma components (0/3) and in endometrial stromal sarcomas (0/5). CONCLUSIONS: These data suggest that intragenic PTEN mutations are involved in the genesis of uterine carcinosarcomas with endometrioid-type carcinoma components but rarely contribute to the pathobiology of uterine leiomyosarcomas.

Sacrocolpopexy--a report on 262 consecutive operations.

OBJECTIVES: This report analyses the outcome and complications of 262 consecutive sacrocolpopexy procedures for the repair of vaginal vault prolapse and enterocele. METHODS: From March 1994 to February 2001, 262 patients underwent surgical repair using a standardised retroperitoneal technique. Initially dura mater strips were used and from the 19th patient onwards, Gore-tex soft tissue patch was used to suspend the vaginal apex to the anterior sacral ligament. Halban-type occluding sutures were placed in the pouch of Douglas. All patients were followed up and the minimum duration of follow-up was 16 months. RESULTS: Vaginal vault prolapse was successfully managed in 259 of 262 patients giving a success rate of 98.8%. In addition, 4 patients had a repeat enterocele that required surgical repair. The overall surgical complication rate was low. Erosion of the patch through the vaginal vault occurred in 10 patients, necessitating removal of the patch. Prolapse did not recur in any of these patients. CONCLUSION: Abdominal sacrocolpopexy is a very successful and safe surgical management of vaginal vault prolapse.

Uterine sarcomas in South African black women: a clinicopathologic study with ethnic considerations.

BACKGROUND: There is considerable evidence for a higher incidence of uterine sarcomas in blacks when compared to whites. However, whether this higher incidence is related to differences in clinicopathologic presentation is not known. PATIENTS AND METHODS: We reviewed slides and clinical charts of 81 patients with a primary diagnosis of uterine sarcoma referred between 1991 and 1999 to Kalafong Academic and Pretoria Academic Hospital. After review, 49 cases remained for study. RESULTS: Uterine sarcomas were distributed between leiomyosarcoma (LMS) (39%), carcinosarcoma (CS) (49%) and endometrial stromal sarcoma (ESS) (12%). LMS and ESS tend to present at an earlier age when compared to CS (respectively p < 0.008 and 0.02). Of women with LMS more women are premenopausal when compared to CS (p < 0.009). Lower abdominal pain is more common in LMS (p < 0.009), whereas bleeding is more common in women suffering from CS (p < 0.01). Lymphovascular space involvement and cervical involvement are more common in CS when compared to LMS. In CS, the carcinoma component has most of the metastatic potential. CONCLUSION: Among black South African women different clinicopathologic features for uterine LMS, CS and ESS are observed. We also present genetic and/or hormonal factors possibly contributing to the pathophysiology of uterine sarcomas in blacks.

Microsatellite instability in uterine sarcomas.

Studies have shown a 15-30% frequency of microsatellite instability in endometrial cancer. In addition, we found a 21% frequency of microsatellite instability in endometrial cancer. Our aim was to investigate the presence of microsatellite instability and loss of heterozygosity in uterine sarcomas. The records of 69 women referred to Kalafong Academic and Pretoria Academic Hospital with a primary diagnosis of uterine sarcoma were reviewed. At histological review of 43 cases with a primary diagnosis of leiomyosarcoma, diagnosis of mitotically active leiomyoma was made in 21. Diagnosis of carcinosarcoma was made in 21 cases and endometrial stromal sarcoma in five. In all cases, genomic DNA was extracted from normal myometrium and tumor and analyzed for microsatellite instability and loss of heterozygosity. High-frequency microsatellite instability was absent in leiomyosarcoma, endometrial stromal sarcoma, and mitotically active leiomyomas and was observed in 1 (5%) carcinosarcoma. Loss of heterozygosity for chromosome 11 was present in 8/48 (17%) of uterine sarcomas, equally distributed between leiomyosarcomas (4/22 = 18%) and carcinosarcomas (4/21 = 19%). There was no loss of alleles in endometrial stromal sarcoma nor mitotically active leiomyomas. In conclusion, it is suggested that tumor suppressor genes may play a role in the tumorigenesis of uterine mesenchymal cells, whereas mismatch repair genes contribute to the carcinogenesis of endometrial cancer.

Uterine carcinosarcoma with melanocytic differentiation.

A 65-year-old black woman was found to have a 3.0 cm endometrial tumor that was a carcinosarcoma with a major epithelial and a less prominent mesenchymal component. The latter was undifferentiated but one focus of chondroid differentiation was noted. The former showed papillary serous differentiation. Melanin pigment was observed in both epithelial and mesenchymal components. Staining with antisera to S100 protein and HMB-45 confirmed the presence of melanocytes. An endocervical focus of tumor also contained melanin. Electron-microscopic studies showed large tumor cells with an irregularly indented nucleus and abnormal giant cytoplasmic melanosomes. Only one case of uterine carcinosarcoma with melanocytic differentiation has been previously reported.

Predicting response to neoadjuvant chemotherapy in patients with cervical carcinoma: can we do without any longer?

The aim of the study was to identify variables that may predict the response to neoadjuvant chemotherapy (NACT) in patients with cervical cancer as maturing data from the literature indicate that this therapeutic strategy might be beneficial to some but harmful to others. Clinico-pathologic variables including age, histology, tumor differentiation, as well as immunohistochemical overexpression of p53, mdm2, c-erbB-2, and cathepsin D in 37 of these patients were evaluated as possible predictors of response to the NACT. Fifty-five patients with stage IIB cervical cancer submitted to two courses of cisplatin/ifosfamide/mesna prior to definitive treatment with radical surgery or radiation therapy were the subjects of this study. The clinical response rate was 80% but none of the variables was able to predict response to NACT. Unless methods are found enabling us to predict response and therefore to identify those patients that could benefit from including NACT in the treatment of locally advanced cervical cancer, only women with primarily resectable tumors should be selected for this multimodality approach as a result of the possibility of cross-resistance with radiation therapy in nonresponders.

The prognostic significance of p53, mdm2, c-erbB-2, cathepsin D, and thrombocytosis in stage IB cervical cancer treated by primary radical hysterectomy.

The objective of this study was to evaluate the value of platelet count, p53, MDM2, c-erbB-2, and cathepsin D immunoreactivity as predictors of lymph node metastasis (LNM) as well as their prognostic significance in patients with stage IB cervical cancer treated by radical hysterectomy between 1991 through 1995. We also report on the outcome of a protocol considering lymph-vascular space invasion (LVSI) in addition to LNM as a strong motivation for adjuvant radiotherapy. A total of 93 patients were the subject of this retrospective study. The incidence of positive nodes was high (30.1%). Thrombocytosis (>/= 400.000/mm3) was present in 6.7% of patients. Positive immunostaining was found for p53 (50.6%), MDM2 (21.7%), c-erbB-2 (14.5%), and cathepsin D (45.8%), but none of them was able to predict LNM. Only thrombocytosis was associated with an unfavorable prognosis: a statistically significant association was shown with relapse-free and overall survival in an univariate analysis (P = 0.0431 and P = 0.0012, respectively) with a tendency to significance in multivariate analysis (P = 0.079 and P = 0.0882, respectively). We postulate that thrombocytosis in early stage cervical cancer could be a marker for subclinical tumor burden. LVSI, regarded as an indication for adjuvant radiotherapy, was no longer associated with poor relapse-free or overall survival, but resulted in a 41% postoperative irradiation rate. Further research is needed to establish the value of LVSI in postoperative radiotherapy decision making.

Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting.

In this randomized, double-blind, parallel group, placebo-controlled, dose-ranging study, we have compared three doses (0.1 mg, 1.0 mg and 3.0 mg) of the 5-HT3 receptor antagonist, granisetron (Kytril), as prophylactic therapy for the prevention of postoperative nausea and vomiting. The aims were to determine the optimal dose of granisetron and to evaluate its safety profile. We studied 527 adult patients, undergoing elective open abdominal surgery or vaginal hysterectomy during general anaesthesia. Antiemetic prophylaxis with a single dose of granisetron 1.0 mg or 3.0 mg resulted in a significant reduction (P < 0.001 compared with placebo) in the numbers of patients experiencing postoperative vomiting, or nausea, or who achieved total control during the postoperative periods 0-6 h and 0-24 h. The two higher doses of granisetron (1.0 mg and 3.0 mg) provided effective prophylaxis against vomiting, with 78% and 77% of patients, respectively, being free from vomiting in the first 6 h after surgery, and 63% and 62% in the first 24 h. This compares with 50% and 34% at 0-6 h and 0-24 h, respectively, in the placebo group. Granisetron was well tolerated and the optimum dose was 1.0 mg.