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F al-Azzawi

Publications and source records attributed to F al-Azzawi.

At least 19 recordsLinked to original sources
PubMed2002

Estrogen and colon cancer: current issues.

Carcinoma of the colon is common and its incidence varies according to the geographical location and dietary habits. The aims of this paper are, first, to review the current epidemiological data on the incidence and mortality of colon cancer in postmenopausal women using hormone replacement therapy (HRT); second, to review the published data on the prevalence of estrogen receptors in healthy and malignant colonic tissue; and third, to examine the available evidence of gene silencing as applicable to this and other neoplastic conditions. Estrogen use confers overall protection, with a reduction in the incidence of colon adenoma and carcinoma of about 30%. Estrogen use reduces the colon cancer-related mortality. The risk of colon cancer is decreased among current and recent users of postmenopausal HRT but the molecular mechanisms involved remain unclear. Estrogen acts either on a single major transformation step in the oncogenetic process, or is involved in multiple events that avert the course of this transformation. Aberrant methylation of the CpG islands in the promoter regions of the estrogen receptor gene, as well as of other genes, is equivalent to the silencing of that gene, with the consequence of inactivation, or reduced expression, of a number of genes downstream, including tumor suppressor genes. This epigenetic mechanism, when reversed, suppresses the growth of cancer cells in vitro and in vivo. The ubiquitous distribution of the estrogen receptor genes and their isoforms, in a tissue-specific manner, opens new avenues for the understanding of cellular behavior in health and disease.

Breast Neoplasms↗
PubMed2001

Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate.

OBJECTIVE: This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms. METHODS: The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study. RESULTS: All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group. CONCLUSION: All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern.

Argentina↗
PubMed2000

Headache at menopause and in hormone replacement therapy users.

OBJECTIVES: To determine the prevalence of headache in menopausal women and to assess factors that may influence headache at menopause and in women using hormone replacement therapy (HRT). METHOD: A questionnaire survey was performed on 1000 consecutive women attending Leicester Royal Infirmary menopause clinics. Weight, blood pressure and smoking status were also recorded. RESULTS: Recurrent headache was common and reported by 850 women; 240 women reported a history of migraine. Most women (n = 617) had headaches more frequently than once monthly and 520 women had had at least one headache in the preceding week. Stress was the most common trigger factor (n = 704). A group of 'hormone-sensitive' women was identified (n = 259) whose headaches became worse at menopause and showed variable response to HRT. Logistic regression models showed reported history of migraine and more difficulty coping with stress to be strong predictors for worse headache at menopause and with HRT. Headache improved with age and increasing diastolic blood pressure. No other significant factors were identified. CONCLUSION: Headache is a substantial problem at menopause and in HRT users. It is difficult to predict which women will develop worse headaches at menopause and with HRT, but a history of migraine and reduced coping with stress were significant factors in this group.

Adaptation, Psychological↗
PubMed1998

Effect of a low-impact exercise program on bone mineral density in Crohn's disease: a randomized controlled trial.

BACKGROUND & AIMS: Physical exercise increases bone mineral density (BMD) in healthy young adults and slows the rate of bone loss in later life. The aim of this randomized controlled trial was to investigate the effect of exercise on BMD in patients with Crohn's disease. METHODS: A total of 117 patients with Crohn's disease were randomized to a control group or a low-impact exercise program of increasing intensity. BMD (g/cm2) was measured at baseline and 12 months at the hip and spine (L2-L4) by dual energy x-ray absorptiometry. RESULTS: Nonsignificant gains in BMD occurred at the hip and spine in the exercise group compared with controls (P > 0.05). In fully compliant patients, BMD increased by 3.54% (7.95%) at the femoral neck, 2.97% (7.7%) at the spine, 4.1% (10.26%) at Ward's triangle, and 7.77% (8.2%) at the greater trochanter. Compared with controls, gain in BMD at the greater trochanter was statistically significant (difference in means, 4.67; 95% confidence interval, 0.86-8.48; P = 0.02). Increases in BMD were significantly related to the number of exercise sessions completed (femoral neck; r = 0.28; 95% confidence interval, 0.10-0.45; P = 0.04). CONCLUSIONS: Progressive low-impact exercise is a potentially effective method of increasing BMD in Crohn's disease. If sustained, the increases in BMD may reduce the risk of osteoporotic fracture.

Adult↗
PubMed1998

Osteoporosis and determinants of bone density in patients with Crohn's disease.

Low bone mineral density (BMD) is common in patients with Crohn's disease; however, the pathogenesis of bone loss and risk factors for osteoporosis are not established. Our aim was to evaluate the clinical, dietary, and nutritional determinants of BMD in Crohn's disease. A cross-sectional analysis of 117 patients with Crohn's disease was undertaken. All patients underwent a clinical and dietary evaluation including assessment of nutritional state and life-style. BMD was measured at the hip and lumbar spine by dual-energy x-ray absorptiometry; and z scores obtained by comparison with age- and sex-matched normal values for the healthy UK population. Multiple regression analysis was used to assess associations between BMD and potential risk factors, allowing for possible confounding variables. Thirteen (11%) patients had osteoporosis (z score < -2), with osteopenia (z score < -1, > -2) in a further 34 (29%). Patients with jejunal disease had significantly lower BMD at the spine (P = 0.03) and femoral neck (P = 0.02) than those with disease at other sites. Mean BMD was significantly lower at the hip of patients with previous bowel resection (diff in means = 0.53, 95% CI -0.97, -0.08, P = 0.02), but type of surgery was not significant. Active disease, menstrual history, diet, level of physical activity, and smoking were not associated with low bone mass. At the lumbar spine, body weight (P < 0.0001), male sex (P < 0.0001), and current prednisolone use (P < 0.02) were independently predictive of low bone mass. Body weight (P < 0.0001), male sex (P < 0.0001), and cumulative steroid dose (P = 0.02) were predictive at the femoral neck. The major determinants of BMD in Crohn's disease are body weight, current steroid use, and cumulative steroid dose. Men with Crohn's disease are at greatest risk of osteoporosis, with jejunal involvement and previous bowel resection also contributing to the low bone mineral density.

Absorptiometry, Photon↗
PubMed1998

Screening for osteoporosis in Crohn's disease. A detailed evaluation of calcaneal ultrasound.

OBJECTIVES: To compare calcaneal broadband ultrasonic attenuation (BUA) and velocity of sound (VOS) in patients with Crohn's disease with an age-matched control population. The validity of BUA as a screening tool for osteoporosis was evaluated and the relationship between BUA and previous fracture studied. DESIGN: Cross-sectional study. BACKGROUND: Since patients with Crohn's disease are at risk of osteoporosis and premature fracture, routine assessment of bone mineral density (BMD) is recommended. Quantitative ultrasound of the calcaneum is an inexpensive and radiation-free means of assessing bone density which also provides information on bone microstructure. METHODS: BUA (dB/MHz) and VOS (m/s) were measured at the calcaneum (CUBAclinical, McCue Ultrasonics, Winchester, UK) and compared with bone mineral density at the hip and lumbar spine measured by dual-energy X-ray absorptiometry (DEXA); 100 patients (42 men) with Crohn's disease and 52 age-matched healthy controls (23 men) were studied. RESULTS: BUA was significantly reduced in patients with Crohn's disease compared with age-matched controls [76.53 dB/MHz (+/-17.3) vs 87.29 dB/MHz (+/-17.9), difference in means = 10.76, 95% CI -16.67, -4.85, P = 0.0004] and was significantly associated with BMD at the spine (r = 0.49, 95% CI 0.32, 0.63, P< 0.0001) and femoral neck (r = 0.54, 95% CI 0.38, 0.67, P < 0.0001). In the diagnosis of osteoporosis (t score <-2.5) BUA had a sensitivity of 66.7% at the femoral neck, with a specificity of 85.6%; sensitivity of BUA at the spine was 75% with specificity 89%. CONCLUSION: Patients with Crohn's disease have reduced BUA compared with an age-matched control population. Calcaneal BUA is significantly associated with BMD at the hip and spine but the correlation is insufficient to recommend ultrasound as a screening tool for DEXA.

Absorptiometry, Photon↗
PubMed1998

Uterine surveillance of asymptomatic postmenopausal women taking tamoxifen.

The aim of this study was to assess the ability of transvaginal sonography (TVS) and office hysteroscopy with sharp curettage to characterize the morphological changes in the uteri of asymptomatic postmenopausal women taking long-term tamoxifen for breast cancer. The overall acceptability of a single-visit screening clinic for these women was also evaluated. Fifty-eight women were recruited from patients undergoing regular follow-up at the Leicester Royal Infirmary for breast cancer. A single-visit clinic was acceptable to 94.8% of these women. Transvaginal sonography detected endometrial thickness of greater than 5 mm in 84.5% of cases, but there was no relationship between total tamoxifen exposure and endometrial thickness. Transvaginal sonography also detected uterine lesions such as fibroids and endometrial cysts in 34.5% of cases. Hysteroscopy detected the latter uterine lesions in 53.4% of cases, with three cases (5.2%) of endometrial polyps also being identified in these women. Sharp curettage sampling of the endometrium produced specimens sufficient for diagnosis in 84.5% of cases; 70.7% of specimens were reported as showing types of 'quiescent' endometrium with 13.8% of specimens showing 'active' endometrium. In the latter group, there was a case of complex hyperplasia detected and also a case with granulomatous endometritis. For each histopathological diagnosis identified, there was a wide range of endometrial thickness recorded by TVS. A single-visit screening clinic involving TVS and hysteroscopy with sharp curettage was acceptable to asymptomatic women taking tamoxifen. However, hysteroscopy was more effective than TVS in detecting endometrial lesions such as polyps, fibroids and cystic areas. Although TVS detected endometrial thickness greater than 5 mm in the majority of cases, there were no malignancies detected and, for each histopathological classification, there was a wide range of endometrial thickness associated. Thus, the isolated use of TVS is insufficient for screening the endometria of these women.

Curettage↗
PubMed1997

The Leicester Endometrial Needle Sampler: a novel device for endometrial and myometrial junctional zone biopsy.

A 48-cm-long, fine (16 gauge) needle was purpose-built to our design for full-thickness endometrial sampling. It is driven by a high-speed cutting device that has a two-step action-loaded spring, and is adjusted to a penetration depth of 16 mm. Pain and tolerance were assessed on a visual analogue scale. The histologic diagnosis obtained by this device, the Leicester Endometrial Needle Sampler, was compared with that of Pipelle endometrial sampling in 40 patients at the end of panoramic hysteroscopy under local anesthesia. The patients' mean age was 51 years (range 39-60) and the mean parity was 2.4 (range 0-6). The mean (+/-standard deviation) pain score was 3.7 +/- 2.2 and the mean tolerability score was 4.4 +/- 3.6. The technique helped to procure a full-thickness endometrial biopsy in all cases, from targeted areas including the myometrial junctional zone, with 100% efficiency.

Biopsy, Needle↗
PubMed1997

Differing responses in blood pressure over 24 hours in normotensive women receiving oral or transdermal estrogen replacement therapy.

OBJECTIVE: To examine the effects of oral and transdermal estrogen replacement therapy (ERT) on ambulatory 24-hour blood pressure (BP) recordings. METHODS: In a nonrandomized, prospective study, 90 normotensive, oophorectomized women, ages 30-59 years, underwent ambulatory 24-hour BP measurements at study entry and after 3 and 6 months of either oral (n = 50) or transdermal (n = 40) ERT. RESULTS: In the women receiving transdermal estrogen, we observed a change in mean nighttime systolic BP of -4.2 mmHg (95% confidence interval [CI] -7.7, -0.7; P = .039) after 6 months, treatment. There was a change in mean daytime diastolic BP after 3 months (-3.3 mmHg; 95% CI -5.5, -0.9; P = .016) and 6 months (-4 mmHg; 95% CI-6.8, -1.2; P = .014), and in mean nighttime diastolic BP after 3 months (-3.8 mmHg; 95% CI -6.6, -0.9; P = .027) and 6 months (-4.4 mmHg; 95% CI -7.1, -1.7; P = .005). No significant BP changes were observed in the women taking oral estrogen. Although the statistical power to detect a change of 4 mmHg at the 5% significance level was 90% for diastolic BP, it was weaker for systolic BP (63%) in this group. However, in more than one-third of the women receiving either treatment, a statistically significant increase in BP was observed. CONCLUSIONS: Transdermal ERT was associated with a reduction in mean ambulatory BP, whereas oral treatment did not alter BP. Although the overall effect of estrogen was to lower BP, individual responses were variable, and BP increased in more than one-third of the women on either treatment. Therefore, long-term monitoring of ambulatory measurements may be required.

Administration, Cutaneous↗
PubMed1997

The relation of hand skin-fold thickness to bone mineral density in patients with Crohn's disease.

OBJECTIVES: In healthy postmenopausal women, the association of skin-fold thickness (SFT) with bone mineral density (BMD) is well described, and a low SFT is a useful predictor of osteoporosis. In this study the association between hand SFT and BMD in patients with Crohn's disease was assessed; and the potential for hand SFT as a screening test for osteoporosis evaluated. DESIGN/METHODS: In a cross-sectional study, BMD was measured at the hip and lumbar spine by dual energy x-ray absorptiometry (DEXA). SFT was measured on the dorsum of the right hand using Holtain Tanner Whitehouse calipers. One hundred and seventeen patients (48 male) with Crohn's disease and 50 (25 male) controls were studied. RESULTS: There was a significant correlation between hand SFT and BMD (expressed as t scores) at all four measured sites (lumbar spine r = 0.41, P < 0.0001, 95% CI 0.25-0.55, Ward's triangle r = 0.38, P < 0.0001, 95% CI 0.21-0.53, trochanter r = 0.33, P < 0.0001, 95% CI 0.16-0.48, femoral neck r = 0.38, P < 0.0001, 95% CI 0.21-0.53). On stepwise regression analysis, the association remained significant after correcting for age, weight, menstrual status and current steroid use (P < 0.05). Hand SFT was significantly lower in patients with Crohn's disease than controls (difference in means 0.51 mm, 95% CI 0.3-0.72, P < 0.0001). Mean hand SFT was significantly lower in patients with osteoporosis compared to patients with normal BMD (difference in means 0.74 mm, 95% CI 0.33-1.15, P < 0.001), as was that of osteopenic patients compared to patients with normal BMD (difference in means 0.28 mm, 95% CI 0.01-0.55, P < 0.05). In the diagnosis of osteoporosis, the sensitivity of hand SFT ranged from 29% to 93%, with specificities of 54% to 95%. CONCLUSIONS: Hand SFT is independently associated with BMD in Crohn's disease and is lower than in age-matched healthy subjects. Hand SFT in combination with other easily measurable confounding variables might be useful in screening for osteoporosis in patients with Crohn's disease.

Adult↗
PubMed1996

Immunohistochemical and hysteroscopic assessment of postmenopausal women with uterine bleeding whilst taking Tibolone.

The gonadomimetic steroid Tibolone, is currently widely used for the treatment of menopausal symptoms. Up to 20% of women have been reported to have episodes of bleeding whilst on therapy. We investigated 37 cases who experienced bleeding episodes whilst on Tibolone and compared these to six cases who experienced no bleeding whilst on therapy and who underwent similar investigations in the course of a clinical study. All women underwent a diagnostic hysteroscopy and an endometrial biopsy, under a local anaesthetic. The endometrium was assessed by histology and with immunohistochemical markers for cellular proliferation (Ki67, PCNA), Heat Shock Protein 27 (HSP27) and bcl-2. There were 17 women with intracavitary lesions on hysteroscopy (including one in the control group), 10 with polyps, five with fibroids, two with congenital uterine anomalies. Histological diagnosis was not obtained in 16 cases. The high incidence of uterine polyps in the group who bled on Tibolone suggests an etiologic relation. The staining pattern with HSP27 demonstrated an oestrogenic effect. There were no differences in the bcl-2 immunoreactivity between those who bled and those who did not bleed on treatment which suggests absence of a link. Similarly, there were no differences in the expression of the proliferation markers. We conclude that episodes of bleeding in patients receiving Tibolone for hormone replacement therapy, whilst warranting investigation, should not cause undue concern.

Adult↗
PubMed1996

Thrombophilia and lipid profile in post-menopausal women using a new transdermal oestradiol patch.

OBJECTIVE: To assess the changes, over a 6-month period, in serum lipoproteins, apoproteins and coagulation factors, induced in post-menopausal women treated by a new transdermal oestradiol patch. METHODS: Fifty-three hysterectomised, healthy, post-menopausal women were treated by a new transdermal patch designed to deliver 50 micrograms of 17 beta oestradiol per day (Gynaderm, Shire Developments). One patch was applied twice weekly. RESULTS: Forty-two patients completed the study. There was no significant change in the level of total cholesterol, triglycerides, HDL or LDL. There was a significant rise in the level of ApoAI after 3 months on therapy but this was not sustained after 6 months; there was also a significant drop in the level of ApoAII after 6 months on treatment. The changes in ApoB and Lp(a) were not statistically significant. There was a significant drop in the level of antithrombin III and of protein S, and a significant rise in factor VII. The drop in the level of fibrinogen and of protein C were not statistically significant. CONCLUSION: The transdermal route of oestradiol administration causes minimal changes in lipoprotein metabolism. The statistically significant changes in the thrombophilia profile parallel those observed with oral HRT, but, similarly, may not reflect clinical significance. The potential of transdermal oestrogens as cardioprotective agents is yet to be determined.

Administration, Cutaneous↗
PubMed1996

Carotid plaque regression on oestrogen replacement: a pilot study.

OBJECTIVE: To investigate the effect of unopposed oestrogen on atheromatous carotid plaques. SUBJECTS: Seventeen postmenopausal women with known carotid disease. METHODS: Carotid intimal thickness and plaque length and thickness were measured prior to and following 3 and 6 months of treatment, using Duplex ultrasound. A total of 22 plaques were followed up. RESULTS: There was a reduction in plaque length after 3 (-8.14%, p = 0.001) and 6 months (-28%, p = 0.001) of treatment. The reduction in plaque thickness (-18%, p = 0.004) was significant after 6 months of treatment. Reductions in intimal thickness were not statistically significant. CONCLUSION: Our results suggest that oestrogen replacement is associated with significant plaque regression.

Aged↗
PubMed1996

Endometrial responses to hormone replacement therapy: the bleeding pattern.

Little information is available concerning the response of the endometrium to exogenous sex steroid therapy, particularly in the post-menopausal state. In this study we examined the variability of the bleeding pattern in 103 post-menopausal women receiving cyclical sequential combined hormone replacement therapy (HRT) over 6 months. All patients kept menstrual diary cards to record the onset, duration and subjective assessment of the severity of bleeding. We defined a cycle as starting from the commencement of treatment till the day of onset of bleeding. Two groups were identified amongst 99 women who experienced bleeding: those with a mean cycle length of 29 or more days (late bleeders, n = 50) and those with shorter mean cycle length (early bleeders, n = 49). The former were characterized by less variability in cycle length and bleeding that was of shorter duration. Four women experienced no bleeding. There were no significant differences between the two groups in age, year since the menopause, weight, height, body mass index (BMI), parity, or in the previous use of HRT. The only significant difference was in their smoking habits. This suggests a possible link of a hypo-oestrogenic state to poor cycle control.

Adult↗
PubMed1996

Hysteroscopy or ultrasound?

The methods of evaluation of the uterus and in particular of the endometrium are the subject of a heated debate, but only because those who argue are trying to establish one single technique which is all-encompassing and 100% accurate. Such specifications are very hard to identify in any technique and consequently we have to have an open mind as to what the patient needs and what combination of methods are to be used to achieve the diagnostic goal.

Biopsy↗
PubMed1995

Abnormal uterine bleeding on hormone replacement: the importance of intrauterine structural abnormalities.

OBJECTIVE: To examine the importance of submucous myomas and endometrial polyps before and after menopause and in abnormal withdrawal bleeding on hormone replacement therapy (HRT). METHODS: Between May 1991 and May 1993, women presenting with abnormal withdrawal bleeding on HRT (n = 106), menstrual problems in pre-menopause (n = 92), or postmenopausal bleeding (n = 33) underwent diagnostic outpatient hysteroscopy for the presence of intrauterine structural abnormalities. The findings were compared with a control group of post- and perimenopausal women without bleeding problems (n = 183). RESULTS: When compared with women who had normal uterine cavities, the presence of submucous myomas was associated with a threefold increase in the risk of abnormal menstrual bleeding in premenopausal women (odds ratio [OR] 3.34, 95% confidence interval [CI] 1.77-6.43; P < .001) and a twofold increase in the risk of abnormal withdrawal bleeding in post- and perimenopausal women (OR 2.4, 95% CI 1.25-4.53; P = .004). This did not seem to be related to the number of myomas detected. The frequency of endometrial polyps was not found to be significantly higher in women who had menstrual disorders or abnormal withdrawal bleeding on HRT. Postmenopausal bleeding without hormonal stimulation was not significantly associated with submucous myomas or polyps. CONCLUSION: As increasingly more women request HRT, bleeding problems presenting pre-menopause can no longer be expected to resolve "naturally" after menopause. In the presence of submucous myomas, these women will continue to have a higher risk of abnormal withdrawal bleeding when treated with hormone replacement, whereas endometrial polyps are not associated with an increased bleeding risk. Hysteroscopic assessment of the uterine cavity and subsequent counseling as to the risk of heavy or prolonged bleeding will be helpful in their future management and may improve compliance.

Adult↗
PubMed1995

Effect of a new cyclical sequential postmenopausal HRT on lipoprotein, apoprotein and thrombophilia profile.

We examined the changes in lipoprotein, apoprotein, and thrombophilia profile in postmenopausal women using a new cyclical sequential combined HRT regimen. The study medication consisted of two tablets of Hormonin (oestriol 0.27 mg, oestrone 1.4 mg and oestradiol 0.6 mg), daily and norethisterone (1 mg) BP (Shire Developments) for the last 12 days of every 28 day cycle. Serial fasting blood samples were collected at the beginning of the study and, thereafter, at 3-monthly intervals for 1 year, each patient acting as her own control. Thirty-five healthy postmenopausal women completed 1 year of follow-up and had a complete set of fasting blood samples. The lipid profile; total cholesterol, triglycerides, HDL, LDL, Apo AI, Apo AII, Apo B and Lp(a), as well as the coagulation parameters; antithrombin III, factor VII, fibrinogen, protein C and protein S, were measured at each occasion. There was a statistically significant drop in total cholesterol and LDL levels. Lp(a) level dropped after commencing treatment and remained below baseline for the rest of the study. The initial increase in Apo AII was not maintained for the duration of the treatment. The changes in Lp(a) and Apo AII were not statistically significant. The level of protein S dropped significantly throughout the study. The changes in other coagulation factors were not statistically significant. The effect of this hormonal combination on the lipid parameters is favourable, and although the change in protein S is striking, its clinical significance remains unclear.

Adult↗