Enhanced expression of cytokines may play a fundamental role in the mechanisms of immunologically mediated recurrent spontaneous abortion.

OBJECTIVES: To determine circulatory levels of IL-1 beta, TNF alpha, IFN-gamma and Neopterin in immunologically mediated recurrent abortion. DESIGN: Blood samples were withdrawn from both groups of first trimester recurrent abortion and controls for the determination of serum IL-1 beta, TNF alpha, IFN-gamma by the corresponding IRMA and serum neopterin by a double antibody RIA. SETTING: Department of Obstetrics & Gynecology, Cairo University Hospitals. PATIENTS: Thirty pregnant women in their first trimester who presented with inevitable abortion with history of at least 3 prior spontaneous consecutive abortions, in addition to twenty-three pregnant women in their first trimester presented with their first miscarriage due to chromosomal anomalies (controls). Every attempt was made to eliminate the possible known contributing factors of recurrent abortion except for the presence of cervical mucus sperm antibodies which were present in 24 out of 30 cases. INTERVENTIONS: None. RESULTS: Serum IL1 beta, TNF alpha and IFN-gamma levels of the abortion group were significantly elevated when compared to the corresponding levels of controls. The incidence of abnormal high values of these cytokines varied between 40 to 70%. There was no significant difference of serum neopterin between abortion and control groups. The increase of IFN gamma, the most active principle inducing neopterin release, was below the concentration needed for neopterin stimulation. CONCLUSIONS: In view of the proven findings that cytokines do have detrimental effects on implantation, trophoblast proliferation, embryo development and fetal survival, our results suggest a potential mechanism of immunologic recurrent abortion which involves the secretion of IL-1 beta, TNF alpha, IFN gamma and other cytokines by activated endometrial lymphocytes and macrophages in response to either trophoblast or sperm antigens and these cytokines could partially defuse or penetrate into the systemic circulation.

Cervical mucus prolactin levels in normal fertile and infertile women.

Cervical mucus and serum samples were obtained from 42 anovular women and 20 normal ovular fertile women (controls) for the determination of prolactin concentration by a solid phase radioimmunoassay. The former group was subgrouped into 14 galactorrhoeic (9 with oligohypomenorrhea and 5 with amenorrhea) and 28 non-galactorrhoeic (19 with oligohypomenorrhea and 9 with amenorrhea). The level of prolactin in cervical mucus of normally menstruating women was significantly higher than that of serum at P less than 0.0125 (11.68 +/- 0.77 ng/ml and 16.09 +/- 1.65 ng/ml, mean +/- SE, respectively). Serum prolactin level in galactorrhoeic amenorrhea cases was 8.2 times that of controls, while cervical mucus prolactin amounted to 32 times its control value. The rise of cervical mucus prolactin in cases of galactorrhea oligohypomenorrhea was 21 times its control value which is markedly higher than that of serum (1.9 times). The average rise of serum prolactin in the whole group of galactorrhea with abnormal menstrual function was about 4 times the control value, while the average rise of cervical mucus prolactin was about 41 times the corresponding control value. In the cases of galactorrhea with menstrual dysfunction, serum prolactin level may be normal in 50% of cases, while cervical mucus prolactin is strikingly elevated in 100% of cases. The possibility of pituitary adenoma should be considered if the level of serum or cervical mucus prolactin exceeds 100 ng/ml and 600 ng/ml respectively. The possible physiological role of cervical mucus prolactin and its source are discussed.

Serotonin metabolism and depression in oral contraceptive users.

Serotonin and nicotinic acid ribonucleotide metabolic pathways of tryptophan metabolism were studied before and after tryptophan load test in thirty women using oral contraceptive steroids for a period of 2 to 5 years. Ten of them were suffering from depression. Another ten healthy women participated in this study as a control group. Twenty-four-hour urinary excretion of serotonin, 5-hydroxyindole acetic acid and total 5-hydroxyindoles were estimated as indices of serotonin pathway metabolites, while xanthrenate excretion was determined as an index of tryptophan oxygenase pathway. Plasma cortisol, urinary 17-oxosteroids and 17-hydroxycorticosteroids were determined to assess adrenal cortical function. Urinary creatinine output was assayed to check the adequacy of 24-hr urine collection. The changes induced by oral contraceptive steroids on tryptophan and corticosteroid metabolism were correlated with the associated depression. Changes in serotonin metabolism were demonstrated in the depression group before and after tryptophan load test, while in the non-depression group before and after tryptophan load test, while in the non-depression group, these changes were only demonstrated after tryptophan load test. Results indicated the alteration in tryptophan metabolism are usually well compensated in the non-depression group but may accentuate or precipitate the development of depression in susceptible women.

A simple method for the early detection of pregnancy: (A) Comparative study with radioimmunoassay of beta-HCG: and (B) Fallacies compared to other immunological pregnancy tests.

A simple, sensitive and reliable non-radioactive method for the detection of hCG in concentrated urine for the diagnosis of early pregnancy is reported. Twenty ml of urine were sampled, filtered and concentrated by ultrafiltration with ultra-microporous membrane under reduced pressure (Immersible Molecular Separator, Millipore Co) and the hCG in the concentrate was detected by the ordinary latex agglutination inhibition method using beta-hCG antiserum to avoid cross-reaction with high levels of hLH and hMG. Concentrated and unconcentrated urine samples taken at different periods of amenorrhoea (1, 2 and 3 weeks) were also tested by two-slide pregnancy tests and one-tube pregnancy test. Blood and urine samples taken at one and two weeks amenorrhea were assayed for beta-hCG by a specific RIA. Results were compared to the new method. Retention characteristics and concentration efficacy of the ultra-microporous membrane were checked by performing recovery experiments using commercial hCG and lyophilization procedure. The new test proved to be more sensitive, specific and reliable than other nonradioactive methods in detecting low levels of urinary hCG for diagnosing pregnancy as early as one week after missed period in regularly menstruating women. In addition, it is simpler and safer than the serum RIA presently used to detect low levels of hCG.

Endocrinologic and psychologic aspects of galactorrhea associated with normal menstrual cycles.

Twelve cases of galactorrhea in women with normal menstrual cycles who were radiologically free of any pituitary adenomas were investigated. Determinations were made for serum thyroid-stimulating hormone (TSH), T3 resin uptake (T3RU), total thyroxine by radioimmunoassay (T4), free thyroxine index (FT4I), norepinephrine, epinephrine, prolactin and urinary luteinizing hormone, total estrogens, pregnanediol and total catecholamines. Psychologic evaluation and assessment were also done using the Middlesex Hospital Questionnaire and the Eysenk, manual dexterity, Bender Gestalt and trial-making scales. Hypothyroidism associated with moderate hyperprolactinemia and anovulation were the main features in eight cases. Associated psychologic disturbances were reported. The other four cases showed significant elevations in serum epinephrine, norepinephrine and urinary total catecholamines with concomitant pathologic scales of anxiety and neuroticism. Thyroxine replacement and psychotherapy are recommended in the treatment of such cases.

The diagnostic value of hysterosalpingography in infertility cases: part 2, the radiological appearance of tubal pick-up mechanism "hand pointing sign.".

PIP: Hysterosalpingography was used to determine the appearance of the fallopian tubes at the time of ovulation. 47 of 50 normal fertile patients showed a characteristic radiological sign, designated the tubal hand pointing sign, at the time of expected ovulation. 6 figures depict this tubal alteration. The tubal hand pointing sign is seen as the normal tube spreads laterally from the uterine corne. The proximal part of the tube is nearly straight, followed by a convoluted intermediate part. The infundibulum and fimbria ovarica are seen pointing to the ovary and ovarian bed. The tubal pick=up mechanism was suggested as the cause of the radiological appearance described. In 2 cases depicted, the distal part of the tube is creeping, snake-like, over the ovarian surface and bed. Hence, it is suggested that absence or distortion of this tubal hand pointing sign may be helpful in the diagnosis of infertility.^ieng

Genital tract bleeding in IUD users and its relation to the device state.

PIP: The relationship between the device state of an IUD and genital tract bleeding was investigated. The investigation was based on data collected from a random 1075 insertions of 30-mm Lippes Loops, which constituted a general incidence of bleeding of 15% in IUD users. In 21% of these cases, the bleeding could not be halted by standard treatments, and the IUD was removed. X-ray, hysterography, and ultrasonography were used to diagnose the IUD state in situ. 75% of the cases requiring IUD removal showed abnormal radiological findings, whereas only 20% of the treatable bleeding cases showed radiological device abnormality. Use-duration was the main factor in the findings; users of IUDs for less than 1 year had abnormal radiological findings in 58.3% of resistant cases and in 29.6% of treatable cases. The corresponding figures among users for periods of time varying from 1-3 years and greater than 3 years were 49.6 and 11.4, respectively, and 86.6 and 66, respectively. Device displacement, distortion, and fractures were the most common radiologically detected abnormalities. In the 2 groups studied, the bleeding pattern varied in amount and type. In resistant cases, metrorrhagia was significant. The increase of vaginal discharge (40.4%), uterine colic (88%), tenderness (25.8%), and RVF (35.5%) was detected in the resistant as opposed to the treatable groups. This increase suggests a uterine factor, i.e., the IUD itself.^ieng

Serum sialic acids in the normal menstrual cycle: a possible test for the prediction of ovulation.

PIP: A test for predicting ovulation is described which is based on measurement of serum sialic acids in normal menstrual cycle. In this study of 7 healthy, fertile women, free, bound, and total sialic acids were determined during various menstrual cycle phases. A second experiment was performed on 109 oral contraceptive pill users who were taking combined formulations for less than 1 year, 1-2 years, and 3-5 years. In addition, urinary luteinizing hormone determinations were made throughout the menstrual cycles. Bound and total sialic acids showed significant drops from Day 9-13 of the menstrual cycle, whereas they were at an almost constant level during the remainder of the cycle. Based on luteinizing hormone determinations, this drop was seen to coincide with the preovulatory estrogen peak, and just preceded the luteinizing hormone peak. Pill users, with anovular cycles, did not show such a drop in bound and total sialic acids. Hence, determination of serum sialic acids may be a useful tool for ovulation detection.^ieng

Serum cryoglobulins and sialic acids in cervical erosion.

PIP: Serum cryoglobulins and sialic acid levels were determined in 101 women grouped as follows: 1) 25 normal women (control); 2) 36 women with cervical erosion who were pill users; and 3) 40 women with inflammatory cervical erosion. At the same time, 36 normal pregnant women were tested to detect any cryoglobulins in their sera. The level of serum cryoglobulins in those with cervical erosion was 20 times greater than that of the control group, and proved to be highly significant (p 0.005). Twice the normal values were detected in those cases of hormonal erosion. 55% of the pregnant women showed serum cryoglobulins but this was not significant (p 0.05) when compared with those values for hormonal erosion. Insofar as the serum sialic acids were concerned, no significant changes were noted in those cases of hormonal erosion while a signficant rise was seen in those with inflammatory cases (p 0.05). A S.A./C.G. (sialic acid/cryoglobulin) ratio was deduced and based on the discrepancy in serum cryoglobulins and this ratio in the 2 groups displaying erosion, it is possible that these parameters might be useful in diagnosing the inflammatory nature of cervical lesions.^ieng

Effect of low dosage contraceptive pills on serum pseudocholine esterase level.

PIP: The effect on liver functions of oral contraceptives (OCs) was studied by measuring the effect low dosage (Primovlar and Ovulen) OCs on serum pseudocholine esterase, a hepatic enzyme. 62 women, aged 22-40 years, were studied; and these cases were divided into 3 groups based on duration of OC use. The groups included use for less than 1 year, for 1-3 years, and for 3-5 years, as well as a control group (25 healthy non-OC users). The effect of parity was also studied, with women grouped into 43 parous (1-5 deliveries) and 19 grand multiparous (more than 5 deliveries). Venous blood samples were obtained from each case at 1-week intervals for the determination of pseudocholine esterase levels. The mean value of serum pseudocholine esterase in controls was 110 U+ or -20. Mean values for the respective OC users were 107+ or -18.76 (less than 1 year), 100+ or -19.05 (1-3 years), and 98+ or -19.77 (3-5 years of OC use). Only the 3-5 year group was statistically significant in its difference (P .025). In terms of parity, a statistically significant decrease was detected in the grand multiparous cases P .025). It is emphasized that, based on these findings, great caution should be taken in using succinyl choline during anesthesia for such patients who have used OCs long-term, especially grand multiparas.^ieng

Prognostic value of certain enzymatic and hormonal assays in threatened abortion.

PIP: The following biochemical indices were evaluated comparatively as predictors of the course of threatened abortion: serum oxytocinase, heat stable alkaline phosphatase, leucine aminopeptidase, urinary pregnanediol, and urinary estriol. 36 cases, grouped into controls and pathological cases, were studied. In normal pregnancy, there was a progressive rise in the levels of the serum oxytocinase, leucine aminopeptidase, urinary estriol, and pregnanediol. Serum heat stable alkaline phosphatase showed an undifferentiated range of results in nonthreatened pregnancies. In the group of threatened abortion cases, results were, therefore, considered abnormal if 2 or more successive determinations showed progressive reduction in enzyme or hormonal levels, and abnormality was also diagnosed if the results were below the normal range (published tabularly, per gestational week). The prognostic value of these biochemical indices was as follows: of 16 cases with normal serum oxytocinase values, 31.2% aborted, whereas of 10 with abnormal values, 70% aborted. Of 16 cases with serum leucine normal values, 37.5% aborted, whereas Of 10 abnormal cases, 60% aborted. Of 18 cases with normal heat stable alkaline phosphatase values, 55.5% aborted, whereas of 8 cases with abnormal values, 25% aborted. Of 17 cases with normal urinary estriol determinations, 45% aborted, whereas of 9 cases with abnormal values, 44.5% aborted. And of 17 cases with normal pregnanediol levels, 41% aborted, whereas of 9 cases with abnormal values, 55.5% aborted. These results show that combined estimation of serum oxytocinase and urinary pregnanediol is a reliable parameter in anticipating pregnancy outcome in cases of threatened abortion.^ieng

Treatment of Trichomonas vaginitis with a single dose of tinidazole.

PIP: Trichomonas vaginalis is a flagellate protozoon which in women commonly causes vaginal itching; burning, and a frothy, offensive and seropurulent yellowish discharge. Incidence of infection in women varies from 13 to 60%, and is highest during pregnancy because of excess estrogens and in women with poor hygiene or with vaginitis. In men, the incidence ranges from 9 to 37% of persons with urethral discharge. This study presents the results of the use of a single dose treatment of Trichomonas vaginitis with 2.0 gm Tinidazole. 350 women with vaginal discharge from the Gynecology Dept. of Cairo University hospitals were studied. Microscopic study of the discharge revealed T. vaginalis in 103 cases (aged 17 to 48 years). Majority of the clinical complaints (pruritus vulvae; soreness; sense of fullness in vagina and dysuria) disappeared in all cases after administration of 2.0 gm single dose of Tinidazole. Discharge; dyspareunia and soreness or pain at vulval interoitus disappeared in about 2/3 of cases; improved in about 1/4 and persisted in less than 8% (failure in these cases was attributed to other causes such as cervical erosion; bacterial infections; hormonal or other pathologic lesions in the internal genitalia). Mild gastrointestinal reaction (nausea and vomiting) were observed in 5 cases and transient urticaria in 1 case.^ieng

Diagnosis of intrauterine fetal death by vaginal cytology.

PIP: Papanicolaou and Traut (1943) reported that in vaginal smears, superficial cells increased in number following fetal death. The presence of parabasal cells; leucocytes; histiocytes and the disappearance of navicular cells were also noted. Sosska (1949) reported a decrease in the number of superficial cells with loss of clumping of cells in vaginal smears following fetal death. This study evaluates the colpocytologic pattern in 72 cases of intrauterine fetal death: 22 occurred in diabetic patients and 38 in toxaemic patients; in the remaining cases, fetal death was attributed to other cases of placental insufficiency. Vaginal smears were fixed in 95% alcohol for 20 to 30 minutes then stained with Papanicolaou stain; they were then examined for the following parameters: 1) estimation hormonal pattern (parabasal; intermediate and superficial cells) using the Maturation Index (MI); 2) presence or absence of clumping and its degree, and 3) general background of smear and presence or absence of leucocytes; cellular debris or bacteria. Definite changes in smear pattern were observed using both the MI and the Pyknotid Index (PI). The findings support the use of vaginal cytology in determining intrauterine fetal death if the following characteristics are observed in the smear: 1) well-defined shift of MI to the left with the presence of easily identified parabasal cells; 2) increase in number of superficial cells with rise in PI, and 3) definite reduction in navicular cell count and in degree of clumping regardless of period of gestation.^ieng

Enzymatic and hormonal assessment of foetoplacental unit in normal and complicated pregnancies.

PIP: This study compared and correlated the relationship and dependability of serum oxytocinase, leucine amino peptidase, and heat stable alkaline phosphatase levels as well as urinary estriol and pregnanediol excretion values as placental function tests. 2 groups were studied, those with normal (25 cases) and those with abnormal pregnancies (84 cases). There were 84 cases of pregnancy complications which were matched with control, uncomplicated pregnancies after determining the normal range of the factors under study. Of no significance in predicting fetal status at birth were serum heat stable alkaline phosphatase determinations. Serial assays of urinary estriol were useful predictors of fetal status at birth in 80% of complicated cases; 50% of complicated case outcomes were correctly predicted using the serum oxytocinase value. In complications of diabetes mellitus, the urinary estriol assays were sensitive and reliable indicators of the pregnancy state, whereas in preeclampsia complications, both the serum oxytocinase and urinary estriol assays were of prognostic value. However, serum leucine amino peptidase was of less prognostic significance than the oxytocinase determinations. Pregnanediol assays showed insignificant results as diagnostic aids. For assessing the status of the feto-placental unit, combined urinary estriol and serum oxytocinase assays are the most reliable prognostic indicators.^ieng

Urinary estrogens in postmenopausal Egyptian females.

PIP: This study evaluates the effects of age; body weight, and parity of postmenopausal Egyptian females on ovarian function as monitored by urinary estrogen excretion both total and fractionated. It has been established that urinary estrogens are markedly reduced in the postmenopausal than in the childbearing age. 48 postmenopausal Egyptian females with normal liver and adrenocortical functions were studied. Their ages ranged from 1 to 22 years after menopause. 96 urine samples were collected; 50 from 25 females with body weight ranging from 40 to 90 kg, and 46 from 23 females grouped according to parity. The urine samples were used to determine urinary estrogens (total and fractions); 17-oxosteroids and 17-hydroxy corticosteroids. Fasting blood serum samples were also collected for liver function tests. The mean value of 17-oxosteroids was 6.368 + or - 3.1 mg/24 hours urine; mean value of 17-hydroxy corticosteriods was 9.675 + or - 4.2 mg/24 hours urine. All liver function tests were within normal levels. The findings show that urinary estrogens (both total and basic fractions) are inversely proportional to age to 12 years after menopause. Thereafter, urinary estrogens curve to a constant low level up to 22 years after the last menstrual cycle reported. Bodyweight of postmenopausal females did not correlate with urinary estrogen excretion (P 0.1 between different age groups). Nulliparous subjects had lower values of urinary estrone; estradiol 17 B; estriol and total estrogens than multiparous subjects (P 0.005). This was presumed to be due to their ovarian hypofunction^ieng