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Biomedical subjects

H Fox

Publications and source records attributed to H Fox.

At least 55 records · Page 3Linked to original sources
PubMed1996

Endometrial response in estrogen replacement therapy quarterly combined with a progestogen.

OBJECTIVE: The aim of the study was to investigate the endometrial histology and the bleeding pattern under a hormone replacement therapy regimen with continuous estrogen quarterly (3-monthly) combined with a progestogen. METHODS: In a prospective, double-blind, randomised clinical trial, 30 healthy, postmenopausal women were allocated to one of the three trial preparations. Group I was treated with 1 mg micronized 17 beta-estradiol continuously, group II took 2 mg micronized 17 beta-estradiol continuously and group III took 1 mg and 2 mg 17 beta-estradiol alternating every 42 days (step-up regimen). One treatment cycle was 84 days, during the last 12 days estradiol was combined with 50 micrograms gestodene. The total treatment period comprised two cycles of 12 weeks each. With regard to endometrial histology, the second cycle was the actual study cycle. In each patient endometrial samples were obtained at the following time points: after the withdrawal bleeding in the beginning (day 8-11) of cycle II (Vabra-method), at the end of the estrogen mono-phase (day 70-72) of cycle II(Pipelle-method), and 8-11 days after cessation of all medication (Vabra-method). Histopathological classification was done by two experienced gynaecological pathologists. All patients kept record of their bleeding events in a diary. Analysis of variance and Kruskal-Wallis test were used for statistical analysis of the data. RESULTS: 29 patients were evaluable for the assessment of endometrial histology. Only one sampling procedure (1.2%) yielded an insufficient amount of tissue. In each treatment group, simple (cystic) hyperplasia was observed exclusively at the end of the estrogen mono-phase (in total 4/29 patients, 14.8%). Hyperplasia disappeared in all cases after the combined estrogen-progestogen phase. No cytological atypia was seen. Fifty-five cycles were evaluable for the bleeding pattern. The onset of the scheduled bleeding (withdrawal bleeding) was in all cycles on day 11 of the combined phase or beyond. Unlike the duration, the severity of the scheduled bleeding episodes was estrogen-dose dependent. In the entire treatment period of 2 x 84 days, breakthrough bleeding occurred in 3 women, totalling 9 days. Spotting occurred rarely and was equally divided among the treatment groups. CONCLUSIONS: A quarterly sequential hormone replacement therapy regimen for women with anintact uterus gives rise to the development of simple hyperplasia without cytological atypia at the end of the unopposed estrogen phase. This occurs independent of the estrogen dose and can be reverted to inactive or atrophic endometrium by the addition of gestodene during 12 days. The combination offers good cycle control. The safety aspects should be investigated further in long-term studies before this regimen can be advocated for routine use.

Analysis of Variance↗
PubMed1995

Role of hepatic carbonic anhydrase in de novo lipogenesis.

The role of carbonic anhydrase in de novo lipid synthesis was examined by measuring [1-14C]acetate incorporation into total lipids, fatty acids and non-saponifiable lipids in freshly isolated rat hepatocytes. Two carbonic anhydrase inhibitors, trifluoromethylsulphonamide (TFMS) and ethoxozolamide (ETZ) decreased incorporation of 14C into total lipids. Both fatty acid and non-saponifiable lipid components of the total lipid were inhibited to approximately the same extent by 100 microM TFMS (29 +/- 0.3% and 35 +/- 0.3% of control respectively in replicate studies). However, neither drug significantly affected ATP concentrations or the transport activity of Na+/K(+)-ATPase, two measures of cell viability. To establish the site of this inhibition, water-soluble 14C-labelled metabolites from perchloric acid extracts of the radiolabelled cells were separated by ion-exchange chromatography. TFMS inhibited 14C incorporation into citrate, malate, alpha-oxoglutarate and fumarate, but had no effect on incorporation of 14C into acetoacetate. Since ATP citrate-lyase, the cytosolic enzyme that catalyses the conversion of citrate into acetyl-CoA, catalyses an early rate-limiting step in fatty acid synthesis, levels of cytosolic citrate may be rate controlling for de novo fatty acid and sterol synthesis. Indeed citrate concentrations were significantly reduced to 37 +/- 6% of control in hepatocytes incubated with 100 microM TFMS for 30 min. TFMS also inhibited the incorporation of 14C from [1-14C]pyruvate into malate, citrate and glutamate, but not into lactate. This supports the hypothesis that TFMS inhibits pyruvate carboxylation, i.e. since all of the 14C from [1-14C]pyruvate converted into citric acid cycle intermediates must come via pyruvate carboxylase (i.e. rather than pyruvate dehydrogenase). Our findings indicate a role for carbonic anhydrase in hepatic de novo lipogenesis at the level of pyruvate carboxylation.

Adenosine Triphosphate↗
PubMed1995

Patterns of deterioration in senile dementia of the Alzheimer type.

OBJECTIVE: To determine rates of decline in Alzheimer's disease. DESIGN: A longitudinal review of patients diagnosed as having dementia during life, tested serially with the Extended Scale for Dementia, and confirmed by autopsy as having Alzheimer's disease. SUBJECTS AND SETTING: Twenty-nine dead patients with Alzheimer's disease from the participants in the University of Western Ontario Dementia Study Project, confirmed at autopsy as having Alzheimer's disease. METHODS: Analysis of the Extended Scale for Dementia data according to a trilinear model. FINDINGS: In the middle phase of the trilinear model, there was a mean annual change of 13% (range, 2.5% to 51.7%). CONCLUSIONS: It is likely that the common method of averaging a group of different individual scores from the initial and middle phases of observation of Alzheimer's disease collapses together individuals at different stages of the disorder, some of whom are in the initial plateau phase and whose conditions are not declining rapidly. The trilinear model of decline avoids this difficulty and the present study provides postmortem confirmed figures on rate of change.

Aged↗
PubMed1995

The Euro-Team Early Pregnancy (ETEP) protocol for recurrent miscarriage.

The underlying causes and rationale for treatment of recurrent abortion are not entirely clear. The Euro-Team early pregnancy protocol was developed as a diagnostic work-up based on the evaluation of risk factors. Possibilities for therapy can be based only on the expectancy that elimination of some risk factors may improve the prognosis.

Abortion, Habitual↗
PubMed1995

Brenner tumour of the vagina.

Polyps of the vagina are rare and are either of inflammatory/reactive or neoplastic origin. A case of extraovarian Brenner tumour of the vagina in a postmenopausal woman, who presented with a vaginal polyp, is described. The polyp was excised and on histological examination, had the triphasic pattern (transitional, glandular and stromal) characteristic of Brenner tumour. The histogenesis of Brenner tumour is discussed in the context of this unusual location and the controversy of its origin.

Aged↗
PubMed1995

Accumulation of extracellular matrix and developmental dysregulation in the pancreas by transgenic production of transforming growth factor-beta 1.

Transgenic mice expressing transforming growth factor-beta 1 (TGF-beta 1) in the pancreatic beta-islet cells directed by human insulin promoter were produced to study in vivo effects of TGF-beta 1. Fibroblast proliferation and abnormal deposition of extracellular matrix were observed from birth onward, finally replacing almost all the exocrine pancreas. Cellular infiltrates comprising macrophages and neutrophils were also observed. Plasminogen activator inhibitor was induced in the transgenic pancreas as well as fibronectin and laminin, partly explaining accumulation of extracellular matrix. TGF-beta 1 inhibited proliferation of acinar cells in vivo as evidenced by decreased bromodeoxyuridine incorporation. Development of pancreatic islets was dysregulated, resulting in small islet cell clusters without formation of normal adult islets; however, the overall islet cell mass was not significantly diminished. Additional transgenic lines with less pronounced phenotypes had less expression of TGF-beta 1 transgene. These findings suggest that TGF-beta 1 might be a mediator of diseases associated with extracellular matrix deposition such as chronic pancreatitis, and this mouse model will be useful for further analysis of the in vivo effects of TGF-beta 1, including its potential for immunosuppression.

Animals↗
PubMed1994

Placental water content and distribution.

The percentage of total placental water (%H2O(T)), maternal (%MBV) and fetal (%FBV) blood volumes, non-vascular extracellular (%EW) and intracellular (%IW) water, and villous histology were studied in placentas from 12 normal term pregnancies after a normal vaginal delivery, 19 caesarean sections at term after a normal pregnancy and history of a previous caesarean section and 47 caesarean sections at term or preterm due to pregnancy complications. Values were derived from change in placental dry weight, maternal and fetal haemoglobin content and 51CrEDTA space after incubation of placental fragments. Normal ranges (mean +/- SD) after term vaginal delivery were: H2O(T) 83.9 +/- 0.2%, MBV 10.9 +/- 0.2%, FBV 7.4 +/- 0.9%, EW 57.3 +/- 1.3% and IW 11.2 +/- 0.6%. %H2O(T) was higher after caesarean section; other measurements were not affected. There were no differences between placentas after 33-37 and after 38-42 weeks gestation. Three of eight placentas after rhesus incompatibility had %H2O(T) above the mean +2SD of term placentas and five of 17 IUGR placentas were below the mean -2SD. The remaining placentas following maternal pre-eclampsia, hypertension, or diabetes had no apparent alteration in %H2O(T). A blind histological diagnosis of 'true' oedema was associated with both a significantly high %IW and %H2O(T). Perhaps this is due to alteration in placental cell volume regulation in certain situations.

Blood Volume↗
PubMed1993

Cathepsin-D expression in cervical carcinoma and its prognostic significance.

An immunohistochemical study was made of cathepsin-D protein expression in each of the three main types of uterine cervical carcinoma (squamous carcinoma, adenosquamous carcinoma and adenocarcinoma) with particular reference to lymph node status and prognosis. Of the 61 cases, 54.1% showed cytoplasmic staining in more than 2.5% of tumour cells counted. Cathepsin-D expression was significantly higher in adenocarcinoma (mean -3.128) than in squamous carcinoma and adenosquamous carcinoma (mean -3.709, p = 0.047 using logit transformation). Cathepsin-D had no prognostic value in any of the three tumour types. No relationship was found between cathepsin-D staining and lymph node status and there was no advantage in adding cathepsin-D values to lymph node status. These results suggest that immunostaining for cathepsin-D protein expression is unlikely to be of use as a prognostic marker.

Adenocarcinoma↗
PubMed1993

Pathology of early malignant change in the ovary.

Our scanty knowledge of the pathology of early malignant change in the ovary is reviewed. The concept of ovarian intraepithelial neoplasia is discussed, and the malignant potential of ovarian cystadenomas is considered. The question of overt malignant change in tumors of borderline malignancy is reviewed. It is concluded that any advance in our understanding and our knowledge of the early stages of malignant change in the ovary will only come from the use of newer techniques that allow a more sophisticated approach than that allowed by purely morphological methods.

Adenocarcinoma↗
PubMed1993

Bilateral ovarian cysts with squamous intraepithelial neoplasia.

We report a case of bilateral ovarian cysts lined exclusively by squamous epithelium showing multifocal intraepithelial neoplasia. The cervix showed synchronous high-grade intraepithelial neoplasia (CIN III). We interpreted the ovarian lesions as squamous carcinoma of borderline malignancy and believe that they are part of a "field change" that also involves the cervix.

Carcinoma in Situ↗
PubMed1993

Primary neoplasia of the female peritoneum.

Primary neoplasms of the female peritoneum may be mesothelial or Müllerian in nature. Primary mesotheliomas may be cystic, benign papillary or diffuse malignant. Primary Müllerian tumours of the peritoneum are thought to arise within the secondary Müllerian system: the overwhelming majority are serous in nature and probably develop from pre-existing endosalpingiosis. Primary peritoneal serous tumours of borderline malignancy are identical histologically to the peritoneal 'implants' found in association with ovarian serous tumours of borderline malignancy, whereas primary peritoneal serous adenocarcinomas are histologically identical to ovarian serous adenocarcinomas. The recognition of a primary peritoneal serous neoplasm of borderline malignancy rests on the presence of either normal ovaries, ovaries containing only a fully benign neoplasm or ovaries showing only minimal surface involvement. The diagnosis of a primary peritoneal serous adenocarcinoma is made if the ovaries are of normal size with either no tumour or only minimal surface involvement: in some cases normal ovaries will have previously been prophylactically removed because of a family history of ovarian cancer. The differential diagnosis between a primary serous adenocarcinoma and a diffuse malignant mesothelioma can be difficult and is often not resolved by either electronmicroscopy or immunocytochemistry.

Female↗