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Biomedical subjects

J M Higham

Publications and source records attributed to J M Higham.

11 recordsLinked to original sources
PubMed2003

Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding.

BACKGROUND: Irregular bleeding affects up to 60% of hormone replacement therapy (HRT) users. The mechanism of this bleeding is not understood. Reduced endometrial microvascular integrity appears to underlie breakthrough bleeding in pre-menopausal women and the aim of this study was to establish whether similar changes are seen in HRT users and hence to elucidate a possible mechanism of irregular bleeding. METHODS: Endometrium from 34 HRT users with amenorrhoea, irregular bleeding or regular bleeding was assessed for endometrial endothelial cell density (anti-CD34), number of blood vessels per mm(2), vascular basal lamina components (laminin, collagen IV and heparan sulphate proteoglycan) and in 32 subjects and 23 controls for perivascular smooth muscle alpha (SMA). Findings were compared with a control population of 29 post-menopausal women not using HRT, other sex steroids or tamoxifen and with no vaginal bleeding. Staining intensity was assessed in a blinded fashion in all immunohistochemical studies. RESULTS: Four significant differences in endometrial blood vessels were observed between HRT users and controls: (i) a significantly lower density of endometrial endothelial cells (EC staining for CD34) per mm(2) was present in HRT users compared with controls (P < 0.001); (ii) endothelial cells (EC) were predominantly organized within blood vessels (83%) in controls but in HRT users EC were dispersed in the tissues with only 29% in organized vessels (P <0.001); (iii) supportive perivascular cell SMA was significantly reduced in 23 post-menopausal HRT users compared with 23 post-menopausal controls (n = 29, P = 0.013) and (iv) an atrophic or inactive histological pattern of endometrium was more frequently seen in the controls (P < 0.001). CONCLUSIONS: These findings support the hypothesis that exposure to HRT profoundly alters endometrial blood vessels, reducing structural integrity thereby predisposing to irregular bleeding in HRT users.

Actins↗
PubMed2001

Congenital absence of portal vein in the fetus: a case report.

Congenital absence of portal vein (CAPV) is a rare abnormality, which may be associated with other abnormalities. We report a case of prenatal diagnosis of absent portal vein confirmed on postnatal ultrasonography and computed tomography scan. The ultrasound features of CAPV include dilated intra-abdominal segment of umbilical vein, dilated inferior vena cava and the presence of hyperechogenic areas in the liver. Blood coming from the umbilical vein directly drains into the inferior vena cava. The dilated intra-abdominal segment of the umbilical vein shows high velocity pulsatile flow, resembling that of ductus venosus. These findings should prompt a careful search for the portal vein and any associated anomalies.

Adult↗
PubMed1999

Clinical associations with objective menstrual blood volume.

OBJECTIVE: To determine the association between simple clinical parameters and objective menstrual blood volume. STUDY DESIGN: A cohort study, in a London teaching hospital. Women complaining of menorrhagia (207) and those who considered their menstruation to be normal (47) were studied. Those with no demonstrable gynaecological pathology had their menstrual blood loss measured using the alkaline haematin technique. RESULTS: Only 49% of 207 women complaining of menorrhagia had a loss of 80 ml or more. There was an increasing incidence of objective menorrhagia with increasing duration of bleeding and use of more sanitary protection items. Increasing height, age and number of intrauterine pregnancies were all associated with increasing menstrual blood volume. Haemoglobin fell with increasing menstrual blood loss. CONCLUSIONS: Despite these clinical associations it is difficult to establish the quantity of menstrual bleeding with certainty without an objective assessment.

Cohort Studies↗
PubMed1993

A comparative study of danazol, a regimen of decreasing doses of danazol, and norethindrone in the treatment of objectively proven unexplained menorrhagia.

OBJECTIVE: Our purpose was to compare the efficacy of the recommended dose of danazol, a reduced-dose danazol regimen, and norethindrone in the treatment of objectively proven menorrhagia. Recurrence after discontinuing treatment was also assessed. STUDY DESIGN: The study was a single-blind, randomized, parallel, comparative study. After a placebo run-in period over two menstrual cycles, 57 patients with a baseline mean menstrual blood loss of at least 80 ml per cycle were randomly assigned to receive one of three therapies: danazol, 200 mg/day (n = 19) for three menstrual cycles; danazol, 200 mg/day for one cycle, 100 mg/day for one cycle, and 50 mg/day for one cycle (n = 19); and norethindrone, 5 mg three times daily on days 19 through 26 of the cycle for three consecutive cycles (n = 19). Patients in whom treatment was successful (those experiencing blood loss < 80 ml) were entered in the follow-up phase of the study, receiving placebo for a maximum of four menstrual cycles. RESULTS: The final menstrual blood loss on treatment was significantly less for those patients who received both danazol regimens compared with those who received norethindrone (p = 0.017 for reducing dose danazol vs norethindrone and p = 0.043 for 200 mg of danazol vs norethindrone). Both danazol treatment regimens were significantly more successful in reducing menstrual blood loss to within the normal range than was norethindrone. The reducing-dose danazol regimen was successful in eight of 17 patients (p = 0.027), and 200 mg of danazol was successful in nine of 19 patients (p = 0.029), compared with the two successes of 18 patients treated with norethindrone. Significantly more recipients of 200 mg of danazol than of norethindrone subjectively rated their treatment to be moderately or highly effective (p = 0.033). Both danazol treatment regimens were associated with a higher incidence of adverse events than was norethindrone therapy, although the number of withdrawals were similar and infrequent in the three groups. CONCLUSIONS: Both danazol regimens were significantly more effective than norethindrone in reducing the excessive menstrual blood loss of women with unexplained menorrhagia. A subjective assessment by patients found that only the 200 mg of danazol was judged to be significantly more effective than norethindrone in controlling the heaviness of menstrual bleeding. The reduced-dose danazol regimen did not appear to markedly diminish the incidence of adverse events compared with the 200 mg of danazol regimen.

Adult↗
PubMed1992

Endometrial phospholipases A2, polycystic ovaries and pelvic pain.

OBJECTIVE: To compare the activity of calcium independent phospholipase A2 in the endometrium of women with polycystic ovaries and in women with normal ovaries, and to investigate the influence of chronic pelvic pain on phospholipase A2 activity. DESIGN: A prospective descriptive study. SETTING: The Samaritan Hospital for Women and the Unit of Metabolic Medicine, St Mary's Hospital Medical School, London. SUBJECTS: 73 women attending the Samaritan Hospital for Women for clip sterilization, infertility, early recurrent miscarriage or pelvic venous congestion. 45 of these women had no pelvic pain, 22 had normal ovaries and 23 had polycystic ovaries diagnosed by ultrasound. The other 28 women had chronic pelvic pain, 14 of them had normal ovaries and 14 polycystic ovaries. INTERVENTIONS: Endometrial tissue was obtained at curettage or from the excised uterus in the proliferative or secretory phase of the menstrual cycle. The activities of calcium dependent (type 1) and calcium independent (type 2) phospholipase A2 isoenzymes were measured in all endometrial samples. RESULTS: In all the women phospholipase A2 type 1 activity, was significantly higher in the secretory phase than in the proliferative phase (P less than 0.001). There was no difference between women with normal ovaries and those with polycystic ovaries at either stage of the cycle irrespective of whether or not chronic pelvic venous congestion was present. In women with normal ovaries, both with and without chronic pelvic pain, phospholipase A2 type 2 activity was significantly higher in the secretory phase than in the proliferative phase (P less than 0.02 and P less than 0.05 respectively) but in women with polycystic ovaries, with and without chronic pelvic pain, there was no significant difference in activity between the two phases of the cycle. Women with polycystic ovaries had markedly higher proliferative phase type 2 activity than women with normal ovaries (P less than 0.001). Secretory phase type 2 activity was similar in all the women investigated. CONCLUSION: These data suggest that phospholipase A2 type 2 activity is increased in proliferative phase endometrium of women with polycystic ovaries but that the increase is not associated with chronic pelvic venous congestion.

Arachidonic Acid↗
PubMed1991

Phospholipase activity in the endometrium of women with normal menstrual blood loss and women with proven ovulatory menorrhagia.

The activity of phospholipase A2 types 1 and 2 and phospholipase C was measured in the endometrium of women with ovulatory menorrhagia and in those with normal menstrual blood loss. In both groups of subjects phospholipase A2 type 1 activity was significantly higher in the secretory phase than in the proliferative phase (P less than 0.001). The median activity (pmol/mg protein/min) for the proliferative phase was 27.6 in normal subjects and 40.4 in women with ovulatory menorrhagia and for the secretory phase the median activity was 144.5 in normal women and 138.1 in women with ovulatory menorrhagia. There was no difference between the two groups of women at either stage of the cycle. Phospholipase A2 type 2 activity was also higher in the secretory phase than in the proliferative phase (P less than 0.05 for normal subjects and P less than 0.001 for women with menorrhagia). The median activity (pmol/mg protein/min) for the proliferative phase was 94.4 (normal subjects) and 56.6 (women with menorrhagia) and for the secretory phase 148.3 (normal subjects) and 142.5 (women with menorrhagia). The activity of phospholipase A2 type 2 was significantly lower in the proliferative phase of women with ovulatory menorrhagia compared with normal subjects (P less than 0.05). Phospholipase C activity (nmol/mg protein/min) was significantly higher in women with ovulatory menorrhagia (median 8.2) compared with women with normal blood loss (median 5.5) (P less than 0.01).

Endometrium↗
PubMed1991

The medical management of menorrhagia.

Menorrhagia is a common problem which may result in chronic anaemia and cause considerable social embarrassment. Various medical treatments are available to reduce excessive blood loss, thus lessening the effects of this benign yet debilitating condition. In this article these drugs and their potential beneficial effects are reviewed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

Assessment of menstrual blood loss using a pictorial chart.

Objective menstrual blood loss measurements (in ml) were compared with the score obtained from a pictorial blood loss assessment chart (PBAC) which took into account the degree to which each item of sanitary protection was soiled with blood as well as the total number of pads or tampons used. Twenty eight women used the chart during 55 menstrual cycles and a single observer assessed 122 cycle collections in a similar manner. A pictorial chart score of 100 or more, when used as a diagnostic test for menorrhagia, was found to have a specificity and sensitivity of greater than 80%. Demonstration of the relation between self assessed pictorial chart scores and the objective measurement of blood loss enables us to provide a simple, cheap and reasonably accurate method of assessing blood loss before embarking upon treatment.

Adult↗
PubMedDate not supplied

Risk-benefit assessment of drugs used for the treatment of menstrual disorders.

This article considers the benign yet debilitating conditions of menorrhagia, dysmenorrhoea and irregular menstrual bleeding. Surprisingly little has been reported in the literature concerning these common ailments which can detract from the quality of female life during the reproduction years. Both dysmenorrhoea and menorrhagia are subjective complaints, but despite accurate means of measuring menstrual blood loss such quantification is rarely performed. This lack of diagnostic accuracy is a cause for concern, especially as both medical and surgical treatment are not without risk. The therapeutic alternatives which are commonly prescribed in an attempt to rectify such menstrual disorders are discussed. These include the nonsteroidal anti-inflammatory agents, the combined oral contraceptives, danazol, progestogens, antifibrinolytics, haemostatics, luteinising hormone releasing hormone analogues and clomiphene. The results of clinical trials which have utilised these various agents are considered in terms of both the effectiveness of treatment and its potential adverse effects.

Anti-Inflammatory Agents, Non-Steroidal↗