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Biomedical subjects

J Moodley

Publications and source records attributed to J Moodley.

304 records · Page 17Linked to original sources

Knowledge of cervical cancer screening and use of cervical screening facilities among women from various socioeconomic backgrounds in Durban, Kwazulu Natal, South Africa.

The value of screening for cervical cancer has been proven. Such screening in developed countries has achieved a decrease in incidence and mortality by about 80%. Although screening facilities are available in certain parts of developing countries, the incidence of cervical cancer remains very high and many patients present with late stage disease. The study was performed among women from different socioeconomic circumstances (low, middle, and upper social/financial backgrounds). The assessment was performed by means of a questionnaire. The majority of patients from lower socio-economic circumstances with multiple risk factors were not aware of cervical screening or facilities available for this purpose. However, in spite of knowledge of cervical screening and the availability of such services, the majority of women (87%) from higher social and educational backgrounds did not undergo cervical screening. Most patients resided within a 12-kilometer radius of a facility that either provided or could potentially provide screening. Although some patients (36.7%) had had a screening test performed at some time in the past, only 27.3% of patients reported having had a Pap test. This was due to failure on the part of the healthcare giver to disseminate information to the patient regarding the reason and value of cervical screening. Among women from higher socioeconomic groups, the level of education was better and knowledge of the Pap test was not age-dependent. We conclude that the mere provision of a cervical cancer screening service is not sufficient to ensure successful uptake since screening is a multifaceted entity. Improvement of socioeconomic and educational circumstances should improve the uptake of a screening program only if the healthcare giver provides appropriate information to the patient and the patient takes the initiative to avail themselves of such screening.

Adolescent↗

Transcatheter angiographic embolization for the control of massive pelvic hemorrhage due to gestational trophoblastic disease: a case series and review of the literature.

Pelvic hemorrhage, either uterine or vaginal, secondary to gestational trophoblastic disease (GTD) can be catastrophic and sometimes fatal. Surgical intervention, however, such as resection of vaginal lesions or internal artery ligation are invasive and not without untoward events. Angiographic embolization is emerging as a practical, safe, effective, and less invasive technique with excellent results. This case series describes four patients with internal or external hemorrhage due to GTD. Angiography and embolization was performed using the modified Seldinger technique with gelfoam particles. The advantages of this method include outpatient procedure, conscious sedation, and minimal discomfort to the patient with excellent results. We conclude that angiographic embolization should be the method of choice in such circumstances and should form part of the therapeutic armamentarium of every interventional radiologist.

Adult↗

Gestational trophoblastic syndrome: an audit of 112 patients. A South African experience.

Gestational trophoblastic disease (GTD) represents a spectrum of histologically distinct entities including molar pregnancy and choriocarcinoma. The incidence of GTD varies in different parts of the world with high incidences in countries like Japan (2 / 1000 pregnancies). With the advent of sensitive assays for detection of serum beta human chorionic gonadotrophin (HCG) and ultrasound, GTD can now be detected earlier in pregnancy. To date no studies have been reported from South Africa regarding the epidemiology, management, and outcome of patients with GTD. This study was a retrospective audit based on 112 patients with GTD treated at King Edward VIII Hospital, Durban, South Africa. Clinical records of patients were reviewed with regards to presentation, investigation, management and outcome. Of 112 patients, there were 78 patients (70%) with hydatidiform mole and 34 patients (30%) with choriocarcinoma. The mean age of patients was 28.5 years (SD 8.1 years). The majority of patients were Black females (94.6%) while 4.4% were Asian and 1% Coloured females. The most common presenting symptom was vaginal bleeding (93.8%). There were 74 patients (66.7%) who had a previous normal term pregnancy and only two patients (1.8%) had previous molar pregnancies. Suction curettage was the main treatment modality for patients with molar pregnancy while choriocarcinoma was treated primarily with chemotherapy. A total of 72 percent of patients with molar pregnancy and 28 percent with choriocarcinoma had complete remission after initial treatment. Twelve patients died during the course of treatment mainly due to late presentation and advanced metastatic disease. Complete cure was achieved in 89% of patients. Age, parity, previous history, initial uterine size, presence of theca-lutein cysts, and initial betaHCG concentration was not found to be prognostic for persistent trophoblastic disease. In the present study, the incidence of molar pregnancy and choriocarcinoma was 1.2 / 1000 and 0.5 / 1000 deliveries, respectively. This is much lower than those quoted from countries such as Japan. However, the incidence quoted from our study may be overestimated as this was a hospital-based study and most of the uncomplicated deliveries occur in referring centers. Only 20% of patients in this study were above the age of 35 years with a mean age of 28.5 years. The majority of patients were of Black African ethnic origin mainly due to the fact that our hospital is a referral center for Black patients. Similar to other studies, the majority of patients with molar pregnancy were treated with suction curettage while the majority of patients with choriocarcinoma were treated with chemotherapy. Overall, spontaneous remission was achieved in 60% of patients with molar pregnancy and an overall complete cure was achieved in 89% of patients.

Adult↗

The role of steroid contraceptive hormones in the pathogenesis of invasive cervical cancer: a review.

Invasive cervical cancer remains a leading cause of morbidity and mortality, especially among women in the developing world where screening is either deficient or absent. Of all agents linked to the causation of this disease, high-risk human papillomavirus (HPV) appears to be the strongest factor. However, not all women with HPV develop cervical cancer. Steroid contraception has been postulated to be one mechanism whereby HPV exerts its tumorigenic effect on cervical tissue. Steroids are thought to bind to specific DNA sequences within transcriptional regulatory regions on the HPV DNA to either increase or suppress transcription of various genes. Although some earlier studies were reassuring as no increased incidence of cervical cancer was observed, subsequent research has shown a causative association, especially among long-term users. The role of steroids was further enhanced by the discovery of hormone receptors in cervical tissue. Some earlier studies of oral contraceptive steroids found no increased risk, even after controlling for other risk factors, including smoking and number of partners. However, prospective studies have shown a greater progression of dysplasia to carcinoma-in-situ with more than 6 years of oral steroid contraceptive use. Similar findings were also evident from other work, including the Royal College of General Practitioners Oral Contraception Study. The WHO Collaborative Study of Neoplasia and Steroid Contraceptives showed a relative risk of 1.2 for invasive cancer in users of the long-acting progestational contraceptive, depo-medroxyprogesterone acetate. However, in users of more than 5 years duration, an estimate of 2.4 was reported. The upstream regulatory region (URR) of the HPV type 16 viral genome, mediates transcriptional control of the HPV genome and is thought to contain enhancer elements that are activated by steroid hormones. It has been shown that steroid hormones bind to specific glucorticoid-response elements within HPV-DNA. Experimental evidence has revealed that high-risk type HPV 16 are able to stimulate the development of vaginal and cervical squamous cell carcinomas in transgenic mice exposed to slow-release pellets of 17 beta-estradiol in the presence of human keratin-14 promoter. Squamous cell carcinomas developed in a multi-stage pathway only in transgenic mice and not in nontransgenic mice. The E6 oncoprotein of HPV 16 has been shown to bind to the p53 tumor suppressor gene and stimulate its degradation by a ubiquitin-dependent protease system. Steroid hormones are thought to increase the expression of the E6 and E7 HPV 16 oncogenes, which in turn bind to and degrade the p53 gene product, leading to apoptotic failure and carcinogenesis. However, the molecular basis of this remains to be proven.

Contraceptives, Oral, Hormonal↗

Successful use of anti-retroviral therapy in combination with cytotoxic chemotherapy for persistent molar pregnancy: a case report.

Due to the HIV pandemic, the chances of finding gynecological malignancies in HIV-infected women are increased. This poses management and ethical dilemmas as the treatment for such malignancies are likely to further decrease their immunity. Gestational trophoblastic disease occurs predominantly among young women and has excellent response to chemotherapy. However, such therapy is not possible if their immunity (CD4 counts) is markedly depressed. The patient described presented with persistent molar pregnancy and had low CD4 count. She was given antiretroviral therapy and once the CD4 count had risen to acceptable levels cytotoxic chemotherapy was administered. She received a total of 13 cycles of chemotherapy with no significant untoward effects. After a 6-month follow-up period the patient was well with a negative serum betaHCG level and CD4 count above 200. We conclude that HIV-infected women with gestational trophoblastic disease may be safely treated with cytotoxic chemotherapy provided anti-retroviral therapy is concurrently administered to boost immunity.

Adult↗

Non-puerperal uterine inversion in association with uterine sarcoma: clinical management.

Non-puerperal uterine inversion due to uterine sarcoma is a rare entity often diagnosed at the time of surgery. Patients may present with pelvic pain, vaginal discharge, or hemodynamic shock. Clinically, the diagnosis may be suspected if there is a large vaginal mass and difficulty in palpating the cervix. Four surgical procedures have been described to manage non-puerperal uterine inversion, two by the abdominal route and two by the vaginal route. The Haultain procedure performed abdominally is preferred for uterine sarcomas as it facilitates reversion of the uterus vaginally or excision of the pedicle and removal of the prolapsed tumor vaginally. We describe a patient with this condition managed by the Haultain procedure.

Diagnosis, Differential↗

Ovarian germ cell malignancy and human immunodeficiency virus (HIV) infection: a case report.

The occurrence of germ cell tumors in patients with human immunodeficiency virus (HIV) infection has not been previously reported. However, with the HIV pandemic in certain parts of the world, this association has become a reality. The approach to management as well as the role of adjuvant radiotherapy and chemotherapy is problematic as many of these therapies are toxic. The appropriate management of such tumors will remain elusive for sometime. The presentation, management, and outcome of ovarian endodermal sinus tumor in a HIV-infected patient is reported.

Adolescent↗

P53 codon 72 polymorphism and BRCA 1 and 2 mutations in ovarian epithelial malignancies in black South Africans.

Mutations in the BRCA and p53 tumor suppressor genes are implicated in the oncogenesis of ovarian tumors although their exact roles remain unclear. Despite recognized ethnic differences in the frequency of ovarian cancer and in genetic polymorphisms between populations, studies carried out so far have focused almost entirely on Caucasian subjects. In this study, undertaken at King Edward VIII Hospital, Durban, South Africa, we examined blood and/or primary epithelial ovarian tumor tissue from 75 black South African women for the presence of the three most commonly occurring BRCA 1 and 2 mutations (185delAG, 5382insC and 6174delT). The p53 codon 72 allele status was also examined and results were compared to a reference cohort comprising 340 ethnically matched subjects. None of the BRCA 1 or 2 mutations were detected in the patient group. The codon 72 Arg allele frequency in lymphocytic DNA was not significantly different compared with the control group. In contrast, in ovarian tumor DNA, the Arg allele was found significantly more frequently than in the controls; this was observed in terms of both Arg allele frequency (45% vs. 31%; P = 0.017) and Arg homozygosity (20% vs. 9%; P = 0.039). Tumors with the more aggressive serous papillary cystadenomatous histology had a markedly higher Arg frequency (45%) than the mucinous cystadenomas (25%). The higher frequency of the Arg allele detected in this study in black South Africans with ovarian tumors suggests a possible role in malignant transformation and may constitute a risk factor for ovarian and other epithelial cancers through mechanisms yet to be elucidated.

Adult↗

Vaginal malignant melanoma: a case report and literature review.

Vaginal melanomas are rare genital malignancies occurring mainly in the 6th and 7th decades of life. In general, they have a worse prognosis than cutaneous melanomas. In the past, various treatment modalities have been recommended including radical pelvic surgery. However, the prognosis is poor in spite of such radical approaches. More recently, more conservative treatment in the form of wide local excision combined with adjuvant chemotherapy, high-dose radiotherapy, and immunotherapy seem to have promising results. We describe a patient with vaginal malignant melanoma treated with conservative local excision as well as adjuvant radiotherapy, chemotherapy, and interferon.

Combined Modality Therapy↗

Gestational trophoblastic syndrome and human immunodeficiency virus (HIV) infection: a retrospective analysis.

The appropriate management of gynecological malignancies in association with human immunodeficiency virus (HIV) infection is not established. To date the reported literature on the subject consists mainly of case reports. Due to the increasing prevalence of HIV infection, especially in sub-Saharan countries, the chances of finding both conditions in the same patient has produced management and ethical dilemmas. This retrospective study describes the management of 12 HIV-infected patients and compares their outcome with 29 non HIV-infected patients. The mean age of the non HIV-infected patients was 30 years (range 16-56 years), while the mean age of the HIV-infected patients was 32 years (range 20-47 years). In terms of risk factors, there were 72% of non HIV-infected women in the high-risk category compared to 50% of HIV-infected women (P = 0.468). All patients who received treatment had CD4 counts greater than 200 cells/microl. Two HIV-infected women who did not receive any form of chemotherapy due to low CD4 counts (41 cells/microl and 84 cells/microl) demised of their disease. The majority of women (86% non HIV-infected & 90% HIV-infected) received lfewer than 10 cycles of chemotherapy to attain cure. Most side effects were minor. None of the HIV-infected patients who received chemotherapy demised of their disease. In total, irrespective of risk category, there were 38 patients (93%) who were cured of their disease by chemotherapy including 10 HIV-positive patients. All patients were alive and free of disease at their last follow-up visit. Although the numbers are small, it is proposed that HIV-infected patients with choriocarcinoma and a reasonable degree of CD4 counts (>200cells/microl) should receive standard therapy.

Adolescent↗

The interaction between steroid hormones, human papillomavirus type 16, E6 oncogene expression, and cervical cancer.

Various risk factors have been implicated in the causation of cervical cancer including human papillomavirus (HPV), the early genes (E6 and E7 ) of which encode the main transforming proteins. Studies have suggested that steroid hormones may enhance the expression of these genes leading to loss of p53 gene-mediated cell apoptosis. A total of 120 cervical tissue samples were obtained from patients with proven cervical cancer. Patients who used depo-medroxyprogesterone acetate steroid contraception were recruited as part of the steroid arm. Only HPV DNA type 16 samples were used for the study. Controls included three cell lines (CaSki, SiHa, & C33A) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal housekeeping gene. Of 120 patients, there were 111 patients with HPV type 16 identified. Of this number, RNA was present in 63 samples. There were 30 women (30/63) who used steroid contraception. In relation to patients who used contraception, HPV 16 E6 gene expression was present in 79% (n = 23) and 88% (n = 30) of steroid users compared to nonusers, respectively. In total there were 25 patients (40%) with expression of the HPV 16 E6*I gene and 30 patients with expression of the E6*II gene. There were 57% of steroid users (n = 17) who had expression of the E6*I/E6*II gene, compared to 52% (n = 17) of nonusers (P = 0.800). From a molecular level, this study does not confirm the role of injectable progesterones in cervical carcinogenesis.

Adolescent↗

Effects of antihypertensive drugs on the unborn child: what is known, and how should this influence prescribing?

This review discusses the use of antihypertensive drugs in acute and long term treatment of hypertensive disorders of pregnancy, including their placental transfer and adverse effects on the fetus. All antihypertensive agents cross the placental barrier and are present in varying concentrations in the fetal circulation, with varying resultant effects on fetal metabolism. Antihypertensive drugs that are lipid soluble will pass through the placental barrier with ease whereas the most polar will not. Placental transfer diminishes under conditions that decrease the surface area or increase the thickness of the placenta. Highly protein-bound drugs form complexes which impair placental transfer while unbound drugs cross the placenta easily. The ionised drug form is highly charged and cannot cross lipid membranes while the un-ionised form can easily cross the placenta. A decrease in placental blood flow can slow down the transfer of lipid soluble drugs to the fetus. Close monitoring of the fetal and maternal condition is necessary for the rest of the pregnancy after antihypertensive therapy is commenced. Methyldopa is the initial drug of choice for long term oral antihypertensive therapy in pregnancy. Neither short term nor long term use of methyldopa is associated with adverse effects. In the short term (<6 weeks) beta-receptor antagonists are effective and well tolerated provided there are no signs of intrauterine growth impairment. ACE (angiotensin converting enzyme) inhibitors are contraindicated in the second and third trimesters of pregnancy because they are teratogenic. Intravenous dihydralazine is widely used for rapid reductions of severely elevated blood pressure. The use of nifedipine concurrently with MgSO4 must be approached with caution because the combination is associated with severe hypotension, neuromuscular blockade and cardiac depression. In the last decade, knowledge of antihypertensive drugs used in pregnancy has improved and new drugs, e.g. calcium antagonists, which have been shown to have great potential for use in pregnancy, have been introduced. Safety for the fetus with newer drugs has not yet been adequately evaluated. Currently, well established and cost effective drugs such as methyldopa (long term use) and intravenous dihydralazine (rapid reduction) are the agents of choice to treat hypertensive disorders of pregnancy.

Adult↗

Carbohydrate metabolism in African women with twin pregnancy.

Carbohydrate metabolism was evaluated in 21 twin pregnancies and in 21 women with singleton pregnancies. The groups were matched for age, weight, parity, and period of gestation. A 100-g oral glucose tolerance test was performed on all 42 subjects. No significant differences in venous plasma glucose responses were found between singleton and twin pregnancies. The only significant difference between the insulin responses of the two groups was a lower plasma insulin concentration at 60 min in the twin group (P less than 0.03).

Adult↗

Maternal deaths due to pre-existing cardiac disease.

Heart disease in pregnancy is an uncommon problem in the developed world, but reaches a high prevalence in poor countries. In South Africa 0.65% of all pregnant women have heart disease, and there is an unacceptably high morbidity and mortality rate (9.5% ). Rheumatic heart disease accounts for most of this mortality, mitral stenosis being the commonest lesion. In April 2000 the National Committee on Confidential Enquiries into Maternal Deaths (NCCEMD) reported that close to half of non-obstetric maternal deaths in South Africa were due to cardiac disease. Several preventable factors were identified that precipitated decompensation and could have accounted for this high mortality. Among them, lack of adequate antenatal evaluation, uncontrolled fluid infusion, failure to identify the patient at risk, and failure to recognise the risk of autotransfusion in the postpartum phase, were contributing factors. This report of the problems seeks to address ways in which these difficulties may be rectified.

Cause of Death↗

Fulminant amoebic colitis: a favorable outcome.

Fulminant amoebic colitis (FAC) is often associated with a poor outcome (reported mortality between 55% and 87.5%). We present the outcome of a conservative surgical approach to the management of this condition. Over an 8-year period (January 1992 to December 1999), 23 patients with FAC were managed and prospectively evaluated by a surgical unit at King Edward VIII Hospital, Durban. There were 19 males and 4 females with a mean age of 36 years (range, 18-57 years). Unrelenting abdominal signs was the indication for surgery in all patients. A preoperative diagnosis of FAC was made in 20 patients; in 1 patient the diagnosis was made intraoperatively. FAC was not recognized in 2 patients. The 21 patients diagnosed with FAC were managed by perileal antegrade colonic lavage; 2 patients underwent total colectomy and ileostomy. Following colonic lavage and ileostomy, there was a 95% survival rate (N = 20). Both patients who underwent total colectomy and ileostomy died postoperatively. Patients underwent restorative surgery at a mean period of 7.2 weeks (range, 6-10 weeks) following the initial surgery. The extent of colonic stricturing invariably warranted colonic resection. This included total colectomy (N = 12), right hemicolectomy (N = 5), left hemicolectomy (N = 2), and right and transverse colectomy (N = 1). The overall survival rate of the 23 patients presenting with FAC was 82.6% (N = 19). Early recognition of FAC and a conservative surgical approach are associated with a favorable outcome. Resectional surgery in FAC has a potentially fatal outcome and should be avoided.

Adult↗

Granuloma inguinale (donovanosis) in women. An analysis of 61 cases from Durban, South Africa.

BACKGROUND AND OBJECTIVES: Granuloma inguinale (GI) appears to be making a resurgence in South Africa. Local cases were reviewed in order to determine an increasing prevalence and whether differences appeared between pregnant and non-pregnant women. STUDY DESIGN: Retrospective analysis of clinical records of patients attending a large tertiary teaching hospital, serving an underprivileged population. RESULTS: Sixty-one women with GI were diagnosed over a 3-year period. The most common clinical presentation was genital ulceration in both pregnant (88.5%) and nonpregnant (45.7%) patients. The next most common presentation was genital tract bleeding (19.7%), which occurred mainly among nonpregnant women. The vulva was the most frequent anatomical site involved (54.1%), in both pregnant (88.5%) and nonpregnant (28.6%) women. Multiple sites of infection (vulva, vagina, cervix) occurred only among nonpregnant women. Fourteen of 33 (42.4%) patients whose syphilis serology results were available had reactive tests. Erythromycin and tetracycline were the most common single antimicrobial agents used for therapy and response varied according to site and size of lesion. CONCLUSIONS: This study confirms our clinical impression of the increasing prevalence of GI, especially among women in Durban, South Africa. The protean manifestations of the disease are demonstrated with sharp distinctions between pregnant and nonpregnant women and there was a high prevalence of concomitant syphilis.

Adolescent↗