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S Manek

Publications and source records attributed to S Manek.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pathologic features of uterine leiomyomas following uterine artery embolization.

Bilateral uterine artery embolization has recently been employed as an alternative to operational treatment of uterine leiomyomas. The pathologic features induced by uterine artery embolization have not been previously described in detail. Usually patients experience symptomatic improvement with a reduction in size of the leiomyomas. This report describes the pathologic features in a series of 10 uterine leiomyomas where tissue was available for histologic examination following uterine artery embolization. Characteristic histologic features within the leiomyomas included massive necrosis, sometimes with dystrophic calcification, vascular thrombosis, and intravascular foreign material that elicited a histiocytic and foreign-body giant cell reaction. In some cases, intravascular foreign material was present elsewhere in the myometrium, the cervix, or paraovarian region. In occasional cases, there were foci of myometrial necrosis and microabscess formation beyond the confines of the leiomyomas. Foci of extrauterine inflammation were also occasionally identified. Histopathologists should be aware of these findings because the use of uterine artery embolization will possibly become more widespread in the future.

Adult↗
PubMed2000

Should tissue from pregnancy termination and uterine evacuation routinely be examined histologically?

OBJECTIVE: To assess the value of routine histological examination of tissue samples collected at termination of pregnancy in the first trimester and emergency surgical uterine evacuation. SETTING: The gynaecological department of a teaching hospital. DESIGN: Prospective study of women attending the gynaecological department in a 12-month period. PARTICIPANTS: All women undergoing a therapeutic first trimester medical or surgical abortion or an emergency surgical evacuation of a failed pregnancy, suspected incomplete spontaneous miscarriage or incomplete induced abortion. MAIN OUTCOME: Association of pre-operative clinical diagnosis and the post-operative histological result. RESULTS: Of 1,576 women studied, the histological report confirmed that products of conception were obtained in 1,465 (93%); in two women (0.13%) molar changes were reported confirming the preoperative diagnosis by ultrasound. Products of conception were not confirmed in the tissue specimens in 0.5% medical terminations, 5% surgical terminations, 10% evacuations following a previous evacuation, 12% evacuations for a failed pregnancy, and 19% evacuations for an incomplete miscarriage. In 87 women (6%), decidua was reported; two of these women had undergone an evacuation for an ultrasound diagnosis of spontaneous miscarriage, but in both a tubal ectopic pregnancy was subsequently diagnosed. CONCLUSION: There did not appear to be any obvious benefit from routine histological examination of tissue removed at termination of pregnancy or emergency uterine evacuation. The histological result was sometimes not consistent with the pre-operative diagnosis and may result in unnecessary further investigation and treatment unless due consideration is given to the clinical presentation.

Abortion, Induced↗
PubMed2000

Expression of the hypoxically regulated angiogenic factor adrenomedullin correlates with uterine leiomyoma vascular density.

Uterine leiomyomas are the most prevalent benign tumor type in women of reproductive age and are one of the most common indications for hysterectomy. The expression of five angiogenic factors, adrenomedullin (ADM), vascular endothelial growth factor (VEGF), acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived endothelial cell growth factor/thymidine phosphorylase, were examined in 91 uteri collected throughout the menstrual cycle; 52 of which contained leiomyomata, and the remainder were normal controls. The microvascular density and endothelial proliferative indices were then determined for each of the uterine sections. ADM and VEGF were the most widely expressed angiogenic factors in the leiomyomas. Furthermore, the expression of ADM and VEGF in the endometrium and myometrium was up-regulated in leiomyoma-bearing uteri compared with controls. Although acidic fibroblast growth factor and basic fibroblast growth factor were expressed in leiomyomas and endometrium in all of the uterine samples examined, they were only expressed in the myometrium of leiomyomata-bearing uteri. Endothelial proliferation in leiomyomas was statistically greater than that of the myometrium and endometrium, both within and between uteri (P < 0.05). The vascular density in the myometrium but not the endometrium was significantly increased in leiomyoma-containing uteri (P < 0.05). Expression of ADM alone correlated directly with vascular density and endothelial cell proliferation index in leiomyomas and myometrium and may account for the high vascularity found in leiomyomas and the myometrium of leiomyoma-bearing uteri. As such, ADM is identified as a novel target for antiangiogenic therapy of these benign, clinically problematic uterine tumors.

Adrenomedullin↗
PubMed2000

Overexpression of H-Ryk in epithelial ovarian cancer: prognostic significance of receptor expression.

H-Ryk is an atypical receptor tyrosine kinase that is expressed in a differentiation-specific manner in epithelial tissues. We have previously shown by in situ hybridization and immunohistochemistry that H-Ryk is overexpressed in malignant ovarian tumors. In addition, we have demonstrated that overexpression of H-Ryk is transforming in vitro and in vivo. To evaluate whether expression of H-Ryk is a prognostic factor in epithelial ovarian cancer, we carried out a retrospective study of 88 primary malignant ovarian tumors (28 serous tumors, 11 mucinous tumors, 29 endometrioid tumors, 13 clear cell tumors, 3 malignant mixed Mullerian tumors, 1 mixed epithelial tumor, 1 primary peritoneal tumor, 1 undifferentiated tumor, and 1 transitional carcinoma) diagnosed between 1990 and 1993 using immunohistochemistry. On univariate analysis, overall survival decreased significantly with age (P = 0.01); in patients with International Federation of Gynecology and Obstetrics (FIGO) stage II (P = 0.008), FIGO stage III (P < 0.001), and FIGO stage IV (P < 0.001) disease; and in patients with residual disease (residual disease < or = 2 cm, P = 0.007; residual disease > 2 cm, P < 0.001) after surgery. In addition, overexpression of the H-Ryk receptor in malignant epithelium (P = 0.04) and blood vessel (P = 0.01) was associated with a significantly decreased overall survival. H-Ryk blood vessel overexpression (P = 0.03), residual disease > 2 cm (P = 0.006), and residual disease < or = 2 cm (P = 0.01) conferred a significantly shorter progression-free survival. No correlation was found between H-Ryk overexpression and age, histological subtype, degree of differentiation, FIGO stage, or residual disease. Overall, after adjustment for all of the prognostic factors by multivariate analysis (Cox proportional hazards model), residual disease was the most powerful prognostic indicator for overall survival (P < 0.001) and progression-free survival (P = 0.01) in this patient subset. This implies that H-Ryk acts cooperatively with other biological factors in the pathogenesis of ovarian cancer.

Adult↗
PubMed1999

Overexpression of H-Ryk in mouse fibroblasts confers transforming ability in vitro and in vivo: correlation with up-regulation in epithelial ovarian cancer.

Abnormalities in the function of receptor tyrosine kinases (RTKs) have been demonstrated to be important in the pathogenesis of cancer. H-Ryk, a new member of the RTK family, is an unusual RTK in that it is catalytically inactive because of amino acid substitutions of conserved residues in the catalytic domain. We show by immunohistochemistry that it is expressed in the epithelium, stroma, and blood vessels of normal tissues. Evaluation of a panel of 33 primary ovarian tumors (2 benign, 8 borderline, and 23 malignant) was performed. H-Ryk was overexpressed in borderline and malignant ovarian tumors. In serous and clear cell subtypes, there was increased expression in the epithelium, stroma, and blood vessels. Consistent with this observation, overexpression of H-Ryk in the mouse fibroblast cell line NIH3T3 induces anchorage-independent growth and tumorigenicity in nude mice. This implies that overexpression of the receptor can be transforming and may therefore be significant in the pathogenesis of ovarian cancer.

3T3 Cells↗
PubMed1999

Tenascin is differentially expressed in endometrium and endometriosis.

Endometriosis is characterized by the presence of functional endometrial tissue outside the uterine cavity, most commonly on the ovary and peritoneum. The aetiology of endometriosis is not understood, although the adhesion of endometrial cells to the extracellular matrix (ECM) would be expected to play a central role in its pathogenesis. The expression of ECM molecules in endometrium and in endometriosis has been investigated using immunohistochemistry and western blotting techniques. The ECM components collagen IV, laminin, vitronectin, and fibronectin had a similar pattern of expression throughout the menstrual cycle in endometrium and endometriosis. Expression of tenascin was elevated in the stroma of the functionalis region of the endometrium during the proliferative stage of the menstrual cycle and in endometriosis. Tenascin expression in endometriosis was not modulated according to the stage of the menstrual cycle. It is concluded that expression of tenascin is strictly regulated in endometrium and may be important in endometrial regeneration and in the pathogenesis of endometriosis.

Adult↗
PubMed1999

CD44 expression in cervical intraepithelial neoplasia (CIN) and carcinoma.

BACKGROUND: The expression of the CD44 gene is markedly changed in many neoplastic tissues. The identification of tumor-specific CD44 expression patterns may aid tumor diagnosis. METHODS AND RESULTS: The transcription and translation of the CD44 gene were analyzed by reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and by immunohistochemistry. Samples were obtained from 24 normal and 24 neoplastic or malignant human cervical tissues. Southern blot hybridization analysis of RT-PCR products revealed an increase in the size and number of CD44 standard and variant transcripts in malignant cervical tissues compared with corresponding normal tissues. Misprocessing of mRNA was indicated in cervical carcinoma cells by the retention of intronic sequences. Multiple CD44 mRNA and protein isoforms were present throughout carcinoma tissues, whereas localization was restricted to the basal epithelium in normal cervical tissue. Analysis of desquamated cervical cells from cases of cervical intraepithelial neoplasia stages I-III showed progressively deranged patterns of CD44 expression, with more alterations being detected in the more advanced stages. CONCLUSIONS: Marked alterations in CD44 expression occur in cervical tissues during progression to malignancy. CD44 expression analysis could aid the early diagnosis of cervical malignancy using minimally invasive methods.

Antigens, Neoplasm↗
PubMed1999

Absence of a relationship between endometriosis and the N314D polymorphism of galactose-1-phosphate uridyl transferase in a UK population.

An association between the N314D polymorphism of galactose-1-phosphate uridyl transferase and endometriosis has recently been reported in a North American population. To determine whether such an association exists in the UK population, we genotyped 148 women with sporadic (n = 91) or familial (n = 57) endometriosis, a control population of 95 male blood donors and a control group of 53 women with a normal pelvis at hysterectomy. Heterozygosity for the polymorphism was found in 14.9% (22/148) of affected women, 13.7% (13/95) of male blood donors and 11.3% (6/53) of women with a normal pelvis. There was no statistically significant difference in the frequency of the polymorphism between cases and controls in the UK population, even when the cases were divided into groups of moderate-severe disease, sporadic cases or familial cases. We conclude that the galactose-1-phosphate uridyl transferase N314D polymorphism is unlikely to be associated with endometriosis in the UK population.

Adult↗
PubMed1999

Tamoxifen and the endometrium: review of 102 cases and comparison with HRT-related and non-HRT-related endometrial pathology.

Tamoxifen, a synthetic anti-estrogen that paradoxically acts as a partial estrogen agonist on the endometrium, is associated with an increased frequency of proliferative endometrial lesions, including hyperplasias, neoplasms, and polyps. Tamoxifen-related polyps are characteristically multiple and fibrotic. A variety of metaplasias and periglandular stromal condensation may be seen. Relatively few articles have focused on the descriptive morphology of the full range of tamoxifen-associated lesions. The present study further defines the histologic features in both endometrial polyps and nonpolyp endometrium. One hundred and two specimens (including 50 polyps) were reviewed using hormone replacement therapy-related endometrial specimens and conventional polyps as the control groups. The most characteristic findings of tamoxifen-associated lesions included polarized glands along the long axis of polyps (40%), a cambium layer (72%), frequent and diverse metaplasias, staghorn glands (36%), myxoid degeneration (12%), and small glands (36%). Similar morphologic features were identified in the hormone replacement therapy and control groups but to a variable, lesser extent. Overall, the tamoxifen group consisted of 18 cases of hyperplasia (11 complex, 7 simple) and one case each of adenofibroma, adenosarcoma, endometrial stromal sarcoma, and leiomyosarcoma. Although none of the features is diagnostic, the presence of diverse metaplasias, polarized glands, staghorn glands, and a cambium layer strongly suggest tamoxifen exposure especially if a number of these features are present concurrently within the same material.

Adult↗
PubMed1998

PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium.

Tamoxifen is currently the most widely used drug for the treatment of breast cancer, but there now exists considerable evidence that tamoxifen can also induce endometrial hyperplasia in pre menopausal women. We have used PCR differential display on primary human endometrial isolates in an attempt to identify genes induced by tamoxifen but not estrogen. Eight such differentially expressed bands were cloned and sequenced, one of which was found to be the peptide adrenomedullin. We have shown that adrenomedullin is a novel growth factor for endothelial cells and is angiogenic in vivo in the chick chorioallantoic membrane assay. Immunohistochemical analysis of endometrial sections have shown that while macrophages in the endometrium express adrenomedullin at a low level, endometrial macrophages of women receiving tamoxifen strongly express adrenomedullin (P=0.008). We postulate that endometrial induction of the angiogenic factor adrenomedullin by tamoxifen is part of the mechanism by which tamoxifen results in endometrial hyperplasia.

Adrenomedullin↗
PubMed1998

Nerve and blood vessel growth in response to grafted dermis and cultured keratinocytes.

The aim of this study was to study innervation and angiogenesis in response to grafts of dermis and cultured keratinocytes using immunohistochemical techniques. In a porcine model, fresh autologous de-epidermalized dermis and cultured autologous keratinocytes were combined using a two-stage technique, to produce keratodermal grafts. Wounds were encased within skin graft chambers that prevented the influence of the surrounding skin. As grafts contracted, a peripheral rim of granulation tissue became exposed, allowing us to compare the wound bed beneath grafts with that beneath the raw granulating surface. Grafts were studied for 6 weeks. Angiogenesis was studied using antisera to von Willebrand factor to detect endothelial cells. Nerve growth was studied using antisera to S-100, a Schwann cell marker, and to four axonal markers: protein gene product 9.5, C-flanking peptide of neuropeptide Y, calcitonin gene-related peptide, and vasoactive intestinal peptide. In kerato-dermal grafts (n = 28), organization of blood vessels and nerve growth occurred only beneath areas with epidermal cover as compared with the surrounding granulation tissue. Initially, the immunoreactivity to von Willebrand factor was high, but in areas with epidermal cover it assumed a more orderly pattern with fewer blood vessels. Innervation was first detected by S-100 immunoreactivity seen at 1 to 2 weeks, closely followed by that to protein gene product 9.5 and much later to calcitonin gene-related peptide. C-flanking peptide of neuropeptide Y and vasoactive intestinal peptide immunoreactivity were detected in the wound depth surrounding large blood vessels at 4 to 6 weeks. In control wounds that had been either grafted with de-epidermalized dermis alone (n = 10) or allowed to granulate (n = 10), persistently there was high immunoreactivity to von Willebrand factor but minimal immunoreactivity to the neural markers. In conclusion, kerato-dermal grafts become innervated, and beneath their surface there is also vascular organization to resemble normal skin. Keratinocytes themselves may influence angiogenesis and innervation, as both processes failed to occur beneath granulating areas.

Animals↗
PubMed1997

Immunohistochemical expression of inhibin/activin subunits in epithelial and granulosa cell tumours of the ovary.

Dimeric inhibin-A has been shown recently by a sensitive two-site ELISA assay to be a useful tumour marker in granulosa cell tumours of the ovary. It is also elevated in some patients with malignant epithelial ovarian tumours. To identify the precise subunits of inhibin expressed in ovarian tumours, three monoclonal antibodies, R1, E4, and INPRO (against the alpha C-, beta A-, and pro-alpha-subunits, respectively), were evaluated by immunohistochemistry on a panel of six granulosa cell and nine epithelial tumours. All granulosa cell tumours stained positively with E4 and R1, suggesting expression of dimeric inhibin-A; in two patients where serum levels were measured pre-operatively, they were elevated. The tumours also reacted weakly with INPRO, suggesting the presence of precursor forms of the alpha-subunit. Eight malignant epithelial ovarian tumours expressed the beta A-subunit only, as recognized by E4, while one tumour expressed both alpha- and beta A-subunits, which correlated with an elevated serum inhibin-A level. Thus, while granulosa cell tumours express inhibin, the majority of epithelial tumours probably express activin, a result which needs to be confirmed by serum measurements.

Activins↗
PubMed1997

The development of neovascularisation in flap perfabrication with vascular implantation: an experimental study.

Femoral arteriovenous pedicles were implanted beneath the abdominal skin in rats (n = 30) to investigate the development of neovascularisation over time. New vessel formation was assessed by micro-angiography and quantified under light microscopy. Flap viability was assessed by dye injection studies at different time intervals. Two weeks after implantation of the vascular pedicles, neovascularisation was confined to the vicinity of the arteriovenous pedicle only and none of the flaps were viable. At 4 and 6 weeks, 4 out of 6 flaps were viable, with new vessel formation being widespread throughout the subcutaneous tissue. All flaps were viable at 8 and 12 weeks. Neovascularisation in the dermis up to the epidermis was observed after 8 weeks. Neovascularisation in the panniculus carnosus showed a steady increase after 6 weeks. There was a decrease in the total number of vessels at 12 weeks compared to 8 weeks but at 12 weeks the diameters of the vessels were considerably larger. Flap survival was best predicted by the amount of neovascularisation in the panniculus carnosus. In this experimental model, it is concluded that prefabricated flaps should be raised at 8 weeks instead of 4 or 6 weeks after the implantation of an arteriovenous pedicle, to reduce the risk of flap failure.

Angiography↗
PubMed1997

Molecular approaches to diagnosis and management of ovarian cancer.

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.

Biomarkers, Tumor↗
PubMed1997

Measurements of oxygenation and perfusion in skeletal muscle using multiple microelectrodes.

This paper describes an apparatus to measure tissue oxygenation and perfusion (as measured by the wash-in rate of gaseous hydrogen) simultaneously at multiple points in muscle using needle microelectrodes. The development of suitable electrodes and apparatus is described, as well as the development of the method and its validation. In particular, the potential for tissue damage secondary to electrode insertion, the need for in vivo voltammetric determination of the operating potential and the extent of any electrode-tissue and of electrode-electrode interactions are explored, and are shown to be insufficient in magnitude to affect the technique. Its subsequent use to characterise oxygenation and perfusion in rabbit skeletal muscle at rest is also described. In resting tibialis anterior muscle of the rabbit the mean pO2 was 18 +/- 13.3 mm Hg and the mean perfusion was 4.4 +/- 1.3 ml s-1 100 g-1. There was a heterogeneity in simultaneously-measured values of pO2 and perfusion at different points within muscle, and also a temporal variation at the same site. The spans between the highest and lowest simultaneously-measured values of pO2 in muscle ranged from 14 to 80 mm Hg, and for perfusion, from 1 to 12 mls-1 100 g-1. No significant correlation was evident from histological examination between either pO2 or perfusion and surrounding fibre type or capillary density.

Animals↗
PubMed1997

Telomerase activity in human gynaecological malignancies.

AIM: To evaluate whether increased telomerase activity can be clinically useful for detecting malignant cells in a variety of gynaecological specimens. METHODS: Telomerase activity was examined in frozen tissue samples of histologically confirmed lesions of the endometrium, ovary, and cervix. It was also assessed in exfoliated cells in cervical smears from patients with premalignant and malignant lesions and in ascitic fluid obtained from cases with malignant or non-malignant ovarian tumours. RESULTS: Solid tissues from carcinomas were telomerase positive in all specimens of endometrial (6/6) and cervical (6/6) origin, and in almost all from the ovary (12/13). Normal tissues from the cervix (0/5) and the ovary (0/5) were telomerase negative, but samples from normal endometrium were found to show telomerase activity, possibly due to the cyclical regenerative nature of this tissue. Conversely, dissociated cells in cervical smears from preneoplastic and frankly neoplastic lesions rarely showed detectable telomerase activity. Thus smears from patients with malignant tumours were only positive in one of two patients, whereas those from CIN-2 (0/5) and CIN-3 (1/17) lesions and from normal (0/10) samples were almost all negative. Telomerase activity was also scarcely detectable in cells obtained from ascitic fluid from patients with ovarian tumours. CONCLUSIONS: As in many other organs, telomerase activity is increased in solid tissue specimens from malignant tumours of the female reproductive tract, but it is not yet a reliable indicator of the presence of exfoliated cancerous or precancerous cells in clinical specimens from such lesions. Interpretation should be guarded until more extensive studies have been conducted. The data on solid tissues presented here confirm that activation of this enzyme is a major hallmark of the neoplastic process.

Ascites↗
PubMed1997

Histamine H2 receptor antagonist-refractory oesophagitis: the efficacy of long-term omeprazole maintenance treatment.

BACKGROUND: Erosive oesophagitis refractory to high dose histamine H2 receptor antagonists (definition: failure to heal fully after > or = 3 months' treatment with cimetidine 3.2 g or ranitidine 0.9 g) responds well to omeprazole 40 mg daily but frequently relapses when the patients are put back on maintenance H2 receptor antagonists at medium or even high dose (e.g. cimetidine 1.6 g and 3.2 g, respectively). AIM: To investigate the efficacy of maintenance omeprazole 20 mg daily in refractory erosive oesophagitis. PATIENTS & METHODS: In this open, sequential study, patients with H2 receptor antagonist-refractory oesophagitis were healed on omeprazole 40 mg daily and then put on maintenance H2 receptor antagonists (cimetidine 1.6 g or 3.2 g). Relapses were re-treated with omeprazole 40 mg; upon rehealing, patients were put on maintenance omeprazole 20 mg daily for up to 4.5 years. RESULTS: Healing on omeprazole occurred in 38 out of 39 patients (97%) at 12 weeks. Only six of the 38 patients (16%) relapsed (asymptomatic in half) during subsequent maintenance treatment, whereas all had relapsed earlier on high dose H2 receptor antagonists. CONCLUSION: Within the limits of interpretation of an open study, omeprazole 20 mg daily seems effective in maintaining prolonged remission in this group of patients with H2 receptor antagonist-refractory oesophagitis.

Adult↗