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Biomedical subjects

A H Gerulath

Publications and source records attributed to A H Gerulath.

14 recordsLinked to original sources
PubMed2002

Gestational trophoblastic disease.

OBJECTIVE: To provide standards for the diagnosis and treatment of patients with hydatidiform mole and gestational trophoblastic tumours (GTT). OPTIONS: Prognostic factors useful for treatment decisions in GTT are defined with patients classified as low-, medium-, and high-risk groups. OUTCOMES: Improved mortality and morbidity. EVIDENCE: Evidence was gathered using Medline for relevant studies and articles from 1980 to 2001 with specific reference to diagnosis, treatment options, and outcomes. The quality of evidence of Recommendations has been described using the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Periodic Health Exam. RECOMMENDATIONS: 1. Suction curettage is the preferred method of evacuation of the hydatidiform mole (III-C). Post-operative surveillance with hCG assays is essential (II-3B). 2. Low-risk patients with both non-metastatic and metastatic disease should be treated with single-agent chemotherapy, either methotrexate or dactinomycin (II-3B). 3. Medium-risk patients should usually be treated with multi-agent chemotherapy, either MAC or EMA (III-C); single-agent chemotherapy may also be used (III-C). 4. High-risk patients should be treated with multi-agent chemotherapy EMA/CO, with selective use of surgery and radiotherapy (II-3B). Salvage chemotherapy with EP/EMA and surgery should be employed in resistant disease (III-C). 5. Placental site trophoblastic tumour that is non-metastatic should be treated with hysterectomy (III-C). Metastatic disease should be treated with chemotherapy, most commonly EMA/CO (III-C).6. Women should be advised to avoid pregnancy until hCG levels have been normal for six months following evacuation of a molar pregnancy and for one year following chemotherapy for gestational trophoblastic tumour. The combined oral contraceptive pill is safe for use by women with GTT (III-C). VALIDATION: These guidelines have been reviewed and approved by the Policy and Practice Guidelines Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC), the Gynaecologic Oncologists of Canada (GOC), the Society of Canadian Colposcopists (SCC), and by Executive and Council of the SOGC. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada.

Antineoplastic Agents↗
PubMed2000

Effect of tamoxifen treatment on the endometrial expression of human insulin-like growth factors and their receptor mRNAs.

The effect of tamoxifen (Tam) treatment on the endometrial expression of IGF-I and II/IGF-IR and IIR mRNAs was assessed by measuring the levels of expression of these mRNAs in the endometrial samples of Tam-treated postmenopausal breast cancer patients by RT-PCR assays. The levels of these mRNAs were compared with those in normal endometrium and in Type I and Type II endometrial carcinomas (EC). The promoter-specific transcript profiles of IGF-I and II were also elucidated. The levels of IGF/IGF-R mRNAs in the endometrium from Tam-treated patients were found to be comparable with the high levels of these mRNAs observed in the proliferative and early secretory phase endometrium and in the samples of Type I EC. These results indicate that Tam acts as an estrogen agonist in inducing the endometrial expression of these genes. Tam stimulated transcription from the multiple promoters of IGF-I and II, with the exception of IGF-II P2 promoter, in which case the transcription across exon 4 appeared to be inhibited. The profiles of IGF-I and II transcripts of endometrium from Tam-treated patients were similar to Type I EC but differed considerably from those of Type II EC. These results suggest that the Tam-associated ECs are likely to be similar to type I EC and will therefore have a more favorable prognosis.

Antineoplastic Agents, Hormonal↗
PubMed2000

Loss of IGF-II imprinting in endometrial tumors: overexpression in carcinosarcoma.

The genomic imprinting of the maternal allele defines the monoallelic expression of the IGF-II gene in most human tissues. The loss of imprinting (LOI) leading to biallelic overexpression of IGF-II has been reported in several human malignancies, including uterine leiomyosarcoma. To ascertain if LOI occurs in endometrial malignancies, the allelic expression of the IGF-II gene was examined in samples of normal human endometrium (n=22) and endometrial tumors (n=12) by assessing the ApaI polymorphism in cDNA segments amplified by RT-PCR. The biallelic overexpression of IGF-II mRNA, involving activation of all four (P1-P4) promoters, was detected in one normal endometrium and in one endometrial carcinosarcoma. Low level biallelic expression of IGF-II was also detected in two samples of hormone-unresponsive/Type II endometrial carcinomas. The level of IGF-I mRNA in these four samples was low. The IGF-IR mRNA was overexpressed in all endometrial cancers including the carcinosarcoma sample, but not in normal endometrium. These data suggest that LOI associated with overexpression of IGF-II and concomitant overexpression of IGF-IR may play a role in the rare carcinosarcoma of the endometrium.

Carcinosarcoma↗
PubMed1999

Discordant expression of insulin-like growth factors and their receptor messenger ribonucleic acids in endometrial carcinomas relative to normal endometrium.

The inappropriate expressions of insulin-like growth factors (IGF-I and II) and IGF-I receptor (IGF-IR) are implicated in the malignant growth of many cancers. To determine changes, if any, in the levels of expression of IGFs and IGF receptor genes in neoplastic endometrium, relative to normal endometrium, the mRNA levels of IGF-I and II and of IGF-IR and IIR were measured in samples of endometrial carcinomas (EC) and normal endometrium, through all phases of the menstrual cycle, by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assays. In normal endometrium, the mRNA levels of IGF-I were elevated in the proliferative and early secretory phases. The IGF-II mRNAs were relatively high in the proliferative phase, but unaltered through early and late secretory phases. Significantly elevated levels of IGF-II transcripts were observed during the menstrual phase, suggesting a possible role of IGF-II in endometrial regeneration. A positive correlation between the levels of IGF-I and IGF-IR mRNAs, apparent in the samples of normal endometrium, was not observed in endometrial carcinomas. The IGF-IR and IIR mRNA levels were elevated in endometrial carcinoma samples. On the other hand, the IGF-I and II mRNA levels were conspicuously low in many carcinoma samples, which were not associated with hyperplasia (type II EC), but relatively elevated in two other carcinoma samples, associated with adenomatous hyperplasia (type I EC). These results albeit with few samples suggest the possibility that the overexpressed receptor, IGF-IR, could be activated differently in two types of endometrial carcinomas, namely ligand-dependently in type I ECs and ligand-independently in type II ECs.

DNA, Complementary↗
PubMed1997

Endometrial transcripts of human insulin-like growth factors arise by differential promoter usage.

By the application of RT-PCR, we have demonstrated that in the human endometrium mRNAs for insulin-like growth factors, IGF-I and II, and their receptors are expressed not only in the intact endometrium, but also in the freshly isolated stromal and epithelial cells. The expression of multiple transcript forms of the IGF-I and II at various phases of the menstrual cycle, occurs by differential use of all four IGF-I transcriptional start sites, and two of the four known promoter sites of the IGF-II gene. The complete spectrum of transcripts is displayed by the proliferative phase and the menstrual phase endometrium. During the secretory phase, the exon 1 upstream start site of the IGF-I gene and the P2 promoter of the IGF-II gene are not used. Irrespective of the phase of the menstrual cycle, the stromal cells always display the same transcriptional patterns of both growth factor genes as those of the intact endometrium. In contrast, the epithelial cells do not express IGF-I transcript originating from the exon 2 upstream initiation site. These results indicate that the expressions of the IGF-I and II genes in the intact endometrium and stromal and epithelial cells are modulated at the transcriptional level during the menstrual cycle by differential usage of promoters and start sites.

Endometrium↗
PubMed1994

Vulvodynia and psychological distress.

OBJECTIVE: To determine whether women with vulvodynia differ psychologically from women with other vulvar pathology and whether women with essential vulvodynia differ psychologically from women with vulvodynia in whom a cause has been identified. METHODS: Women attending a vulvar clinic were given a package consisting of the Brief Symptom Inventory, the Center for Epidemiologic Studies-Depression Scale, the Barsky Somatosensory Amplification Scale, the Whitely Index for hypochondriasis, and a study questionnaire. A gynecologist and dermatologist then took a careful history and performed a gynecologic examination, colposcopy, biopsies, and laboratory examinations. RESULTS: Vulvodynia patients (n = 50) were more symptomatic than women with other vulvar pathology (n = 32) on questions about interference with sexual function (mean difference 1.29, 95% confidence interval [CI] 0.36-2.23, P = .01) and number of doctor visits (mean difference 1.0, 95% CI 0.12-2.12, P = .03). Vulvodynia patients also scored higher than other vulvar patients on the Whitely Index (mean difference 0.45, 95% CI 0.04-0.86, P = .04) and on the Brief Symptom Inventory anxiety subscale (mean difference 0.31, 95% CI 0.09-0.51, P = .05) and somatization subscale (mean difference 0.29, 95% CI 0.10-0.46, P = .04). Women with essential vulvodynia (n = 32) were more anxious (mean difference 0.28, 95% CI 0.02-0.54, P = .02) and more suggestible (mean difference 0.62, 95% CI 0.48-1.72, P = .05) than women with vulvodynia with a physical cause (n = 18). CONCLUSIONS: Vulvodynia patients are more psychologically distressed than women with other vulvar pathology, and women with essential vulvodynia are more distressed than vulvodynia patients with an identified physical cause. Optimal management of vulvodynia patients should include attention to anxiety reduction, sexual function, normalization of every-day bodily sensations, reassurance about the absence of serious disease, and coordination of clinical care to ensure the maximum benefit from consultations.

Adult↗
PubMed1991

Metabolism of [3H]equilin in normal and malignant human endometrium and in endometrial adenocarcinoma transplanted into nude mice.

One of the main components of conjugated equine estrogens is equilin sulfate and this estrogen in postmenopausal women is metabolized to 17 beta-dihydroequilin, 17 beta-dihydroequilenin and equilenin. To investigate the possibility that some of these estrogens may be formed directly in the target tissues, we studied the in vitro metabolism of [3H]equilin in various types of normal and malignant human endometrium, including adenocarcinoma grown in athymic nude mice. The results indicate that normal and neoplastic human endometrium can form the above three metabolites. The highest level of 17 beta-reduced products were isolated from the normal secretory endometrium. Equilenin was the most abundant metabolite isolated from both the normal and malignant endometrium. The formation of [3H]equilenin indicates the presence of a 6,8(9) steroid dehydrogenase-isomerase in the human endometrium. The formation of 17 beta-dihydroequilin in the endometrium may be of importance as this estrogen is 8 times more potent as a uterotrophic agent than equilin and estrone.

Adenocarcinoma↗
PubMed1986

Poor prognosis metastatic gestational trophoblastic disease: experience with moderate dose methotrexate plus folinic acid rescue as initial therapy.

From 1971 to 1981, twenty patients with poor-prognosis metastatic gestational trophoblastic neoplasia (GTN) were treated with moderate-dose methotrexate (1 g) and folinic-acid rescue (MD-MTX-FAR) as initial therapy. Seven (35%) were cured with MD-MTX-FAR, and salvage chemotherapy was successful in an additional seven, for a total cure rate of 70%. The ultimate outcome is similar to that reported for MAC triple therapy during this era. Hematologic and mucosal toxicity were negligible and no serious complications were encountered. We now use combination chemotherapy in patients with poor-prognosis GTN as first-line treatment. However, these results suggest that there may be advantages to the incorporation of MD-MTX-FAR in combination regimens in place of low-dose methotrexate, because of reduced toxicity and potential benefits for the prophylaxis and treatment of cerebral metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1977

Effect of progesterone and estradiol-17beta on nucleic acid synthesis in vitro in carcinoma of the endometrium.

Nucleic acid synthesis was studied in 26 tumor specimens, during a one-hour in vitro incubation with the addition of progesterone and estradiol-17beta. On the response scale used, deoxyribonucleic acid and ribonucleic acid synthesis decreased linearly as the logarithmic concentration of either hormone increased. Inhibition of nucleic acid synthesis was highly significant (P less than 0.001) at 80 microgram per milliliter of progesterone and at 40 microgram per milliliter of estradiol. No evidence of synergism was found when the two hormones were combined at these concentrations. In Grade I and II tumors, the effect when both hormones were combined approximated the sum of effects of the individual hormones. In Grade III tumors, little difference was seen between treatment groups.

DNA, Neoplasm↗
PubMed1977

Giant ovarian cyst in a dwarf.

The authors describe a case of giant mucinous cystadenoma in a dwarf. The cystadenoma weighed 32 kg, almost half the patient's normal weight, Such tumours are rare and are sometimes mistaken for ascites. They are usually benign, but care should be taken to remove them intact since malignant degeneration of mucinous cysts occurs in 5 to 15% of cases. Understanding of the possible complications allows for a favourable prognosis.

Aged↗
PubMed1977

Infant survival following uterine rupture and complete abruptio placentae.

This report concerns a case of spontaneous rupture of the uterus through a previous cesarean scar with resulting complete abruptio placentae and extrusion of the fetus inside the intact membranes and the placenta into the peritoneal cavity. That the infant survived this dual insult is worthy of reporting.

Abruptio Placentae↗