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Biomedical subjects

B G Lindeque

Publications and source records attributed to B G Lindeque.

At least 19 recordsLinked to original sources

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.

Female↗

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.

Biopsy↗

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.

Adult↗

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.

Antineoplastic Agents, Hormonal↗

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.

Adult↗

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.

Exons↗

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.

Adult↗

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.

Aged↗

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.

Age Factors↗

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.

Adult↗

[Chronic osteomyelitis - a diagnostic dilemma].

Infective skeletal lesions can mimic bony tumours. Bony lesions without periosteal reactions in adult patients with normal leucocyte counts will have a different differential diagnosis from that of children with bony lesions and a periosteal reaction. In the latter, osteomyelitis should be distinguished from Ewing's sarcoma and osteogenic sarcoma. Due to the difficult preoperative diagnosis a retrospective study was undertaken which included 14 patients with the histological diagnosis of chronic osteomyelitis but normal leucocyte count and no periosteal reaction. Radiographs showed cavities in 82%, infiltration in 12% and sclerosis in 6% of cases. All patients who underwent skeletal scintigraphy studies showed increased uptake in the lesions. Magnetic resonance showed increased signal intensity in T2 images. Ordinary radiographs are still the most valuable primary investigation for skeletal lesions.

Adolescent↗

Screening for cervical neoplasia in Mamelodi--lessons from an unscreened population.

AIM: To determine the prevalence of abnormal cervical cytological findings in an unscreened population; to assess patients' awareness of cervical cancer and the importance of early diagnosis; and to evaluate the accuracy of visual inspection of the cervix as a screening method for asymptomatic cervical cancer. STUDY STRUCTURE: Descriptive. SETTING: Mamelodi Hospital, a community day hospital east of Pretoria, serving a black urbanised population that had never been exposed to a routine cervical cytological screening programme. METHODS: One thousand and ninety-five women of reproductive age, who presented with a non-gynaecological complaint, were offered cervical cytological testing and were asked to complete a questionnaire. Visual appreciation of the cervical condition was noted and compared with the cytology report. RESULTS: The prevalence of abnormal cervical cytological findings (low- and high-grade squamous cervical intra-epithelial neoplasia (CIN), excluding human papillomavirus-induced cell changes only) was 54/1,000. Only 2% of the patients had a good knowledge of cervical cancer and cervical screening. Visual inspection of the cervix detected 4 out of 5 cervical cancers in this group, but failed to identify those patients with high-grade CIN. CONCLUSION: This study shows a high prevalence of abnormal cervical cytological findings in a population ignorant about cervical cancer. Recommendations on how to improve this situation are made.

Adult↗

Sacral and non-spinal tumors presenting as backache. A retrospective study of 17 patients.

Among 1302 cases reported to our tumor registry, 78 presented with backache as primary symptom. 17 of these had non-spinal tumors, 7 pelvic, 6 sacral, 3 femoral, and 1 costal. There were long delays in making the correct diagnosis; some patients even had had spinal surgery. The mistakes were the classic ones: poor history, poor physical examination, poor radiological work-up. Analysis of these 17 cases suggests that standard spinal radiographs should include an AP pelvis film and a lateral sacral projection. Patients with persistent radiating pain and normal radiographs should have a Tc-99 scan. The correct diagnosis would have been made in all the cases if this protocol had been followed.

Adult↗

Ionogran--an ionomeric micro implant in bone tumour reconstruction. A clinical evaluation.

A new implant material, Ionogran (Ionos, Medizinische Produkte GmbH & Co. K.G., Germany), is evaluated in a series of 60 cases requiring augmented bone grafting for major bone defects. The material, an ionomeric porous micro implant (IMI), is stable, non-degradable, osteoconductive and biocompatible. It promotes the formation of osteoid and displays a dynamic surface activity which stimulates the process of repair. In the compromised situation of a large cavity following curettage and cryotherapy, Ionogran when mixed with a mulch of autogenous cancellous bone is a valuable filler, providing a direct osteoid bond with host bone, and a permanent scaffold which maintains shape, length and form of the affected part. It replaces allogenic bone grafts and the problems associated with that technique.

Adolescent↗

A properly conducted trial of a ventouse can prevent unexpected failure of instrumental delivery.

A retrospective study over a 5-year period reviewed 71 unexpected failures of instrumental delivery and compared them with a group of 21 trials of ventouse to identify causes for failure and their impact on neonatal outcome. There was a statistically significant difference between the two groups in terms of pre-application assessment of fetal size, maternal pelvis and palpable fetal head above the pelvic brim (P less than 0.00001). There was also a significant difference in neonatal morbidity (P less than 0.01). All 5 neonatal deaths occurred in the failure group and were associated with multiple instrumentation.

Extraction, Obstetrical↗

Osteoid osteoma. Diagnosis, localization, and treatment.

The preoperative insertion of a needle under computed tomographic scan, performed under local anesthesia, is a convenient and important new way to localize the nidus in osteoid osteoma. It necessitates less bone removal, which should reduce the postoperative fracture rate. It should also help to locate the lesion during surgery. Some clinical points and previously unstressed pathologic findings are also discussed.

Aspirin↗

Bizarre parosteal osteochondromatous proliferation of a phalanx.

A rare proliferative osteochondromatous malformation of a proximal phalanx is described. This malformation may mimic the appearance of a sessile osteochondroma or parosteal osteosarcoma on X-rays and may be mistaken for a low-grade osteosarcoma on histology, with disastrous therapeutic consequences. We found that cryotherapy followed by local excision was adequate to remove the tumour.

Arthrodesis↗