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Biomedical subjects

R Markham

Publications and source records attributed to R Markham.

At least 37 records · Page 2Linked to original sources

Recognition of affective facial expressions by children and adolescents with and without mental retardation.

Children and adolescents with mental retardation were compared with children and adolescents without mental retardation on their ability to recognize facial expressions. The groups were matched for either chronological age (CA) or mental age (MA). Children and adolescents with mental retardation recognized facial expressions less accurately than did subjects without retardation who were matched on CA. The MA-matched groups showed no differences in accuracy at the younger MA but a difference was found at the older MA. However, subjects categorized as having cultural-familial retardation did not differ from subjects without retardation matched for MA at either the younger or older MA. Results suggest that children with mental retardation are less able than children without retardation to develop emotional recognition skills by observational learning.

Adolescent

Serum CA-125 levels in women with endometriosis.

Forty-two women with laparoscopically-confirmed pelvic endometriosis (assessed according to the American Fertility Society modified classification) had serum levels of the cell-surface antigen CA-125 measured before, during and after medical therapy with nafarelin acetate or danazol combined with follow-up laparoscopic surgery or laparotomy. Serum levels before treatment (39.3 [SE 6.6] U/ml) were elevated above accepted normal levels in many subjects, and these were highly significantly suppressed during medical therapy with both nafarlin and danazol (13.1 [SE 1.5] U/ml at 5 months); t = 3.198; p = 0.002). Levels tended to rise following therapy but a clear correlation between a rise in serum CA-125 and recurrence of disease was not demonstrated. In 3 individuals treated with nafarelin a dramatic rise in serum CA-125 levels was seen after 2 weeks of therapy. This did not correlate with any exacerbation of symptoms or with any rise in serum oestradiol or with pretreatment AFS scoring. Serum CA-125 levels provide a potential approach to the monitoring of treatment and recurrence in a substantial proportion of women with endometriosis, although preliminary evidence suggests that there will be individual exceptions to any broad correlations.

Antigens, Tumor-Associated, Carbohydrate

Detailed assessment of big big prolactin in women with hyperprolactinemia and normal ovarian function.

Six women with elevated circulating levels of big big PRL (BBPRL) and apparently normal ovarian function were variously studied through a menstrual cycle and menstruation, through pregnancy and suckling, and during stimulation tests with TRH and suppression with bromocriptine. No significant changes in monomeric PRL were demonstrated during the menstrual cycle, but all subjects showed a small and significant rise in BBPRL during the preovulatory phase. High PRL levels were present in day 1 menstrual plasma, but BBPRL was only present in low concentrations. All subjects (n = 5) demonstrated a rise in both PRL and BBPRL during pregnancy, with a consistent tendency for PRL to increase to a proportionately greater extent than BBPRL. One subject exhibited a rise in PRL (by 93%), but not BBPRL, 30 min after suckling. TRH caused a brisk rise in PRL (by 363 +/- 116%) but only a sluggish rise in BBPRL (by 17.5 +/- 7.4%; n = 3). Bromocriptine rapidly suppressed PRL (by 81.8 +/- 34.4%), but only slowly suppressed BBPRL (by 21.0 +/- 8.7% after 6 h; n = 3). Plasma binding studies did not demonstrate any evidence of a circulating specific PRL-binding protein. These data indicate that plasma concentrations of BBPRL may vary under the influence of a number of factors, but are much less sensitive to TRH stimulation, bromocriptine suppression, pregnancy, and suckling than PRL. The occurrence of BBPRL does not seem to be due to a specific circulating binding protein.

Adult

The chick chorioallantoic membrane assay: an improved technique for the study of angiogenic activity.

The chick chorioallantoic membrane assay has been used for many years as an in vivo assay of angiogenic activity. However it has been plagued with the problem of a high incidence of false positive angiogenic responses. In this study the conventional chick chorioallantoic membrane assay was compared with a modification of this technique in a series of batches using a total of 100 eggs. False positive reactions were recorded in 32 out of 50 (64%) using the conventional method and only 11 out of 50 (22%) with the modified method (chi 2 = 17.992; p less than 0.001).

Amnion

Trauma-induced human endometrial prostaglandin concentrations.

Controversy still continues concerning the factors controlling endometrial prostaglandin concentrations measured under different circumstances. In this study an attempt was made to remove serial samples of normal human endometrium and standardise 4 different short incubation periods at room temperature before snap-freezing the tissue. No significant difference was found in the concentrations of PGE2 and PGF2 alpha, or PGE2/PGF2 alpha ratio, of the series of specimens with the shortest incubation (42.7 seconds) compared with the longest (93.1 secs). The most likely explanation for this is that trauma-induced prostaglandin production is such a rapid process that it is generally complete within less than 30 seconds at room temperature. As reported in previous studies, a significant correlation was found between PGE2 and PGF2 alpha concentrations in some specimens. Large and significant variations in concentration of prostaglandins were found between individuals which were partly accounted for by variations in stage of the menstrual cycle at the time of collection.

Biopsy

Measured menstrual blood loss in women with menorrhagia associated with pelvic disease or coagulation disorder.

Fifty-five women with a convincing clinical history of menorrhagia associated with recognizable pelvic disease (40 women) or a confirmed coagulation disorder (15 women) were studied through one or more cycles with measurements of menstrual blood loss volume by a modified alkaline hematin method. Women with leiomyomata almost always exhibited large volumes of menstrual bleeding, which was invariably reduced by myomectomy and sometimes helped by mefenamic acid. Women with other pelvic disease such as endometriosis, adenomyosis, and myometrial hyperplasia also often exhibited genuine menorrhagia that responded to mefenamic acid, whereas others were found to have normal blood loss even when the history was convincing. Some women with coagulation disorders due to platelet dysfunction exhibited gross menorrhagia but others had blood loss within normal limits.

Blood Coagulation Disorders

The measurement of human endometrial prostaglandin production. A comparison of two in vitro methods.

Two in vitro methods for measuring human endometrial prostaglandin production were compared. Endometrial samples from eight patients were incubated over eight hours by a perifusion and a superfusion technique. The collected fractions were assayed by radioimmunoassay for PGE2 and PGF2 alpha. There was no significant difference between the perifusion and superfusion methods for the pattern and amount of PGE2 and PGF2 alpha production with time. Significantly higher production levels of PGE2 and PGF2 alpha were found in secretory phase endometria than in proliferative phase endometria. Histological examination of the tissue specimens by light and electron microscopy showed that both methods caused gross tissue damage after eight hours experimentation. The superfusion method produced more morphological damage than the perifusion method. However, no tissue damage could be detected after one hour of incubation with either method. Over an eight hour period neither the perifusion nor the superfusion technique appears to be a good indicator of in vivo endometrial prostaglandin production. Either technique used for only one to two hours may better reflect the in vivo situation.

Dinoprost

Blood and total fluid content of menstrual discharge.

Twenty-eight regularly menstruating female volunteers made careful collections of their sanitary pads and tampons on a daily basis throughout one menstrual period in such a way that the total fluid volume of the menstrual discharge could be accurately measured independently of the blood loss. The percentage contribution of blood (equivalent to mixed venous blood from the cubital fossa) to the total varied very greatly from woman to woman (1.6 to 81.7%) with a mean of 36.1 +/- 3.6% (+/- SEM). There was a highly significant correlation between total fluid loss and blood loss (r = 0.911, P less than .001). The proportion of blood remained approximately the same for different total volumes and on different days of the cycle. Women using no contraception or who had undergone tubal sterilization had similar ratios of blood to total fluid loss, whereas intrauterine device (IUD) users had a higher ratio (P less than .025) and oral contraceptive users a lower ratio that just reached statistical significance (P less than .05). It seems probable that the major component of the fluid loss that cannot be accounted for by blood is from endometrial tissue fluid rather than vaginal or cervical secretions.

Blood Volume

A preliminary study of factors influencing perception of menstrual blood loss volume.

Sixty-nine women with a convincing complaint of menorrhagia took part in a double-blind treatment trial. Menstrual blood loss was measured and the subject's own perception was carefully recorded. Only 38% had objective menorrhagia with a measured loss greater than 80 ml although 59% would qualify with an upper limit of normal of 60 ml. Overall the measured loss in the "heaviest" periods (69.6 +/- 7.3 ml; mean +/- SEM) were significantly greater than that of the "lightest" periods (42.7 +/- 4.7 ml; p less than 0.001), but there were many major errors in perception by individuals. Perceived daily blood loss volume on a 4-point rating scale gave the following group means and ranges: spotting, 2.5 ml (0.1 to 15.5); light, 5.7 ml (0.1 to 63.1); moderate, 16.1 ml (0.5 to 108.6); very heavy, 22.0 ml (1.4 to 215.8); very wide individual ranges of assessment are illustrated. As a whole the group was also able to distinguish between a day-to-day volume increase or decrease, but again there were many major errors. Some subjects who experienced a reduction in measured blood loss from one day to the next actually perceived this as a large increase. Menstrual pain and duration of bleeding were not found to influence perception of blood loss volume, whereas younger subjects (26 and under) were significantly more likely than older women (37 and over) to regard a moderate loss as very heavy. There was no significant correlation between the number of pads/tampons used and the measured menstrual loss, and some individuals showed extreme variations between blood loss and pad usage. This study suggests that the only reliable assessment of menstrual blood loss volume and changes in volume in women complaining of menorrhagia is obtained by objective measurement of blood loss by a technique such as alkaline hematin extraction.

Adult

Long-term treatment of menorrhagia with mefenamic acid.

Thirty-six women with menorrhagia were treated with mefenamic acid during all menstrual periods for more than 1 year. These women had experienced objective and subjective benefit--menstrual blood loss was reduced and other menstrual symptoms improved during a preliminary 4-cycle double-blind placebo-controlled trial with mefenamic acid (placebo cycles: 65.6 +/- 5.3 ml; mefenamic acid cycles: 45.3 +/- 5.1 ml, mean +/- SEM). This reduction in menstrual blood loss was maintained at 6 to 9 months (49.2 +/- 9.9 ml) and at 12 to 15 months (42.8 +/- 4.8 ml) after the trial. These reductions were significant at the 6- to 9-month (paired t test = 2.18; P less than .05) and the 12- to 15-month interval (paired t test =- 4.40; P less than .001). Significant sustained reductions in blood loss were seen in the women with menorrhagia due to ovulatory dysfunctional bleeding and in those who had undergone tubal sterilization. Significant reductions were also seen in dysmenorrhea, headache, nausea, diarrhea, depression, number of sanitary towels used, and number of mefenamic acid capsules taken. A significant increase in serum ferritin was found between admission and completion of the follow-up trial in 11 women (P less than .01).

Clinical Trials as Topic

Influence of danazol treatment during the luteal phase on pituitary and ovarian function during the subsequent menstrual cycle.

Eight subjects with normal menstrual cycles were treated with danazol (800 mg daily) during one luteal phase to assess the effect on follicular development in the subsequent cycle. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone were measured daily throughout both cycles. Following danazol there was a consistent and significant delay to the preovulatory estradiol (P less than 0.05) and LH (P less than 0.02) peaks and a significant suppression of the early follicular phase FSH (P less than 0.05) and preovulatory estradiol peak plasma levels (P less than 0.05). All other parameters of the post-danazol cycle were indistinguishable from normal. However, there was a small suppression of midluteal phase FSH during danazol treatment, compared with the posttreatment cycle, which was significant for three subjects. It is suggested that the small effect of luteal phase danazol on subsequent follicle development may occur at an intraovarian level through an effect on receptors or enzymes as well as through the small degree of suppression of midluteal phase and early follicular phase FSH.

Adult

Dynamic tests of hypothalamic and pituitary function in women treated with danazol.

Gonadotropin-releasing hormone (GnRH) tests (12 women) and estradiol benzoate stimulation tests (8 women) were carried out before and during short- or long-term treatment with danazol. There was no difference in the height or timing of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peaks following GnRH or estradiol benzoate between any of the treatment groups or between the pretreatment and treatment responses within groups. However, some individuals did show an apparent attenuation of response during treatment. These results indicate that danazol does not produce a profound or consistent suppression of the hypothalamus or pituitary in normal women in the reproductive age group. The impressive clinical effect of danazol may be mediated by additive minor to moderate suppressive effects at each level of the hypothalamic-pituitary-ovarian-endometrial axis.

Danazol

Efficacy of mefenamic acid in patients with a complaint of menorrhagia.

Sixty-nine patients with a convincing history of menorrhagia completed a 4-cycle double-blind randomized placebo-controlled crossover trial of mefenamic acid taken during menstruation. Only 30 of these patients demonstrated objective menorrhagia with a measured menstrual loss greater than 80 ml during the placebo cycles, but the remainder reported passing clots and/or using 2 pads at a time. Fourteen of these women (20%) had a loss of less than 35 ml while taking placebos. This raises serious questions about the establishment of menorrhagia based on history alone. Overall, there was a mean reduction of 28.1% in menstrual blood loss between placebo and mefenamic acid cycles (P less than .001). The greatest reduction recorded was 80%, and most of the large percentage reductions were seen in patients with high loss during placebo cycles. Significant reductions in blood loss (P less than .001) were seen in patients with ovulatory dysfunctional uterine bleeding and menorrhagia that developed after tubal interruption. There was also an indication based on small sample sizes that mefenamic acid reduced blood loss in women with anovulatory dysfunctional uterine bleeding, fibroids, intrauterine devices, and von Willebrand disease. No reduction was seen during the mefenamic acid cycle in the group with a loss of less than 35 ml during the placebo cycle. There was a significant shortening of duration of bleeding (P less than .003). Fifteen patients (21.7%) experienced no objective reduction in blood loss.

Adolescent

Plasma prostaglandin F metabolite concentrations following cervical encerclage.

Peripheral plasma concentrations of 13, 14-dihydro-15-keto prostaglandin F2 alpha (PGFM) were measured in seven women having elective cervical encerclage in an otherwise normal pregnancy. Three of seven patients had a statistically significant elevation of PGFM levels at 60 minutes after commencement of surgery. On the basis that the majority of patients had no significant rise and that there was no objective evidence of uterine contractions post-operatively, the routine administration of prostaglandin inhibitory agents to patients having cervical encerclage cannot be recommended.

Cervix Uteri

Oral vancomycin for antibiotic-associated pseudomembranous colitis.

Nine patients with antibiotic-associated pseudomembranous colitis were treated with oral vancomycin. All had severe diarrhoea, tissue-culture evidence of a clostridial toxin in stool, and typical lesions on sigmoidoscopic examination, despite discontinuation of all antimicrobials for periods of 10 days to 8 weeks. Oral vancomycin was given in doses of 2 g daily. All patients showed a good clinical response with gradual resolution of diarrhoea over 7 days and a rapid decrease in concentrations of the toxin in stools. Follow-up sigmoidoscopies in seven patients showed major improvement or complete clearing of lesions after 7-10 days of vancomycin treatment. The mean concentration of vancomycin in twenty-five stools obtained during treatment was 3100 microgram/g, levels in serum being very low. These results suggest a role for oral vancomycin treatment of antibiotic-associated pseudomembranous colitis which persists for extended periods despite discontinuation of the incriminated antimicrobial.

Administration, Oral

Plasma prolactin levels and ovarian responsiveness to exogenous gonadotropins.

Standard gonadotropin stimulation tests of ovarian function and basal plasma prolactin measurements have been carried out in 151 patients with amenorrhea or severe oligomenorrhea. In 90 of these a standardized multiple pituitary stimulation test, including the prolactin response to thyrotropin releasing hormone, was also performed. There was a tendency for the basal estrogen excretion and the ovarian response to gonadotropin to be lower in patients with hyperprolactinemia. These correlations were weak and did not reach the levels of statistical significance except when compareing the ovariance response in patients with mild hyperprolactinemia to those with moderate or severe hyperprolactinemia. It is concluded that, in women, elevated plasma prolactin levels have little, if any, direct inhibitory influence on the ovariance response to gonadotropins in vivo.

Female