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Interruption of IL-2 signalling is an attractive therapeutic target in autoimmune disorders. In this study we evaluated the effect of a fusion protein composed of IL-2 and caspase-3 (IL2-cas) on NOD mice, as compared with disease induction by cyclophosphamide.IL2-cas was assessed in NOD mice at various ages and in conjunction with cyclophosphamide administration. The effect of IL2-cas on diabetogenic cells was evaluated in adoptive transfer experiments and in cell suspension in vitro.IL2-cas induced apoptosis in T cells expressing the alpha chain of the IL-2 receptor (cluster of differentiation [CD]25) in vitro, with superior survival of T cells expressing CD4 and forkhead box P3 (FOXP3). The fusion protein decreased mixed lymphocyte reactivity, and pretreatment with IL2-cas decreased the efficacy of adoptive transfer of diabetes into NOD severe combined immunodeficiency mice. Administration of one dose of IL2-cas decreased the incidence of diabetes in NOD mice, showing a superior beneficial effect when administered at young age, and effectively blocked induction of hyperglycaemia by cyclophosphamide, reducing the severity of islet inflammation. Administration of IL2-cas caused an acute increase in CD25(-)FOXP3(+) T cells in the lymph nodes, pancreas and thymus in NOD mice, with similar effects in wild-type mice. Administration of IL2-cas after onset of hyperglycaemia resulted in superior survival.Targeted elimination of cells expressing the IL-2 receptor by this fusion protein disrupts the autoimmune pathogenesis in prediabetic and diabetic NOD mice, despite depletion of CD25(+) regulatory T cells. Furthermore, this particular fusion protein is permissive to the development of FOXP3(+) T cells that might contribute to protracted protection from the progression of insulitis and overt hyperglycaemia.

Little is known about the direct effect of chemotherapy on normal peripheral blood leukocytes (PBL) or its contribution to leukopenia. We examined 5'-fluorouracil's (5FU) effect on PBL apoptosis and adhesion molecules' expression in a single-drug solid-tumor model. Possible apoptosis mediators were examined. The study included 32 colorectal cancer patients; apoptosis was determined by annexin-V binding and light-scatter morphology before and after drug infusion. CD18, CD11a, CD11b, and CD63 membranal levels were assayed by flow cytometry. Apoptosis was increased post-5FU administration in neutrophils (PMN), monocytes and lymphocytes (P < 0.05). Levels of Fas receptor and activated caspase 3 did not vary indicating that the process was not mediated by caspase 3 in the timeframe studied. Reduced CD63 on monocytes and decreased CD18 expression on PMN and non-apoptotic monocytes were observed (P < or = 0.05). CD11a,b expression did not vary. Decreased CD18 and CD63 levels were demonstrated in apoptotic and non-apoptotic PBL implying a more direct association with the drug itself.

IL-2-PE40 is a chimeric protein composed of human IL-2 genetically fused to the amino terminus of a modified form of Pseudomonas exotoxin lacking its cell recognition domain. The immunosuppressive efficacy of IL-2-PE40 was demonstrated in several experimental murine transplant and autoimmune models. However, some observations suggested that IL-2-PE40 could not inhibit the humoral response. In this report, we describe the dichotomous effects of IL-2-PE40 on humoral and cell-mediated immune response in a simple, well characterized in vivo model. Although IL-2-PE40 inhibited the cell-mediated delayed type hypersensitivity reaction to SRBC, it increased the humoral immune response to the same Ag. To understand the mechanism of dichotomous action of IL-2-PE40 on the immune response, IL-2R-bearing T cells were treated with IL-2-PE40 in vitro and the cytokine expression was studied at mRNA and protein level. Similar to IL-2, IL-2-PE40 promoted the expression of T helper 1-like (IFN-gamma) as well as T helper 2-like (IL-4, IL-10) cytokines. These in vitro studies show that IL-2-PE40 can induce signal transduction in activated T cells through the IL-2R before exerting its cytotoxic effect. In contrast to DTH reaction, humoral immune response requires T cell help only for a limited period. Therefore, the short-term stimulation of T helper cells by IL-2-PE40 may be sufficient in vivo to mediate a B cell response in the local environment, whereas the DTH reaction and other cell-mediated immune responses are inhibited by the toxin moiety of the chimeric protein.

The assessment of fetal growth is crucial in twin gestations, since the information gained often has an impact on pregnancy management. The measurement of the fetal anatomy by ultrasound enables us to follow the growth and development of the fetus. However, the pattern of fetal growth in twin gestations has not yet been precisely characterized in prospective studies. In this light, we initiated a prospective longitudinal study and sonographically examined 35 patients with twin gestations every 3 weeks from the 15th week until delivery. Multiple biometric parameters were measured, including the femur length, humerus length, ulna length, and tibia length. The results of our study showed that growth of these long bones was not significantly different between twins A and B throughout gestation and that the growth velocity between twins and singletons was not significantly different. The incremental growth, although significantly less in twins than in singletons, was so small that it was judged not to be of clinical importance to warrant the generation of separate nomograms for the evaluation of growth in twin gestations.

Item does not contain fulltext PURPOSE: Halofuginone (tempostatin) is a synthetic derivative of a quinazolinone alkaloid showing anti-angiogenic, anti-metastatic and anti-proliferative effects in preclinical studies. The objectives of this phase I study were to assess the dose-limiting toxicities (DLTs), to determine the maximum tolerated dose (MTD) and to study the pharmacokinetics (PKs) of halofuginone when administered once or twice daily orally to patients with advanced solid tumours. METHODS: Patients were treated with escalating doses of halofuginone at doses ranging from 0.5 to 3.5 mg/day. For pharmacokinetic analysis plasma sampling was performed during the first and second course and assayed using a validated high-performance liquid chromatographic assay with mass spectrometric detection. RESULTS: Twenty-four patients received a total of 106 courses. The 'acute' MTD was reached at 3.5 mg/day, with nausea, vomiting, and fatigue as DLT. The recommended dose for chronic administration was defined as 0.5mg/day with the requirement of 5HT3 antagonists to control nausea and vomiting considered as DLT. Several patients experienced bleeding complications on treatment with halofuginone in which a causal relationship could not be excluded. The PKs of halofuginone were linear over the dose range studied with a large interpatient variability. CONCLUSIONS: In this study the DLT of halofuginone was nausea, vomiting, and fatigue. The recommended dose for phase II studies of halofuginone is 0.5mg administered orally, once daily.

Purpose: To compare the clinical characteristics and survival of Ashkenazi Jewish ovarian cancer patients with and without BRCA1 and BRCA2 mutations. Methods: An unselected series of 118 Ashkenazi Jewish ovarian cancer patients were screened for the three common founder mutations in BRCA1 and BRCA2 . Patient survival and other clinical characteristics of the tumours were compared in patients with BRCA1 or BRCA2 mutations and those without mutations. Results: Twenty-seven individuals with invasive carcinomas were found to have mutations (14 with 185delAG and one with 5382insC in BRCA1 and 12 with 6174delT in BRCA2 ). No mutations were identified in the 20 patients with borderline tumours. For the invasive carcinomas, there was a survival advantage for BRCA1 and BRCA2 patients compared to patients without mutations, though the differences were not statistically significant. There were no significant differences in the histopathological characteristics of the tumours between the patient groups. Conclusion: These results are similar to those of other studies and suggest that ovarian cancer in BRCA1 and BRCA2 mutation carriers may have a distinct clinical behaviour.

Clinical data indicate that tamoxifen (TAM) therapy may cause an increased risk of endometrial pathology in postmenopausal but not in premenopausal women. Molecular mechanisms of the uterotrophic activity of TAM have not been clearly established nor its relevance to apoptosis in endometrial cells. The present study was implemented to evaluate the apoptotic effect of TAM on primary endometrial cell cultures in the presence or absence of steroid hormones (SHs). A total of 14 primary endometrial cell cultures were established and maintained both with and without SHs. Cell cultures were treated for 24 h with either 20 microM TAM or 10 nM estradiol. Apoptotic cells presented in a pre-G1 peak and the expression of bcl-2 were studied using flow cytometry. All endometrial cell cultures maintained in a SH-containing environment, except one, responded to TAM by a significant increase (P = 0.03) in the pre-G1 cell fraction, indicating a proapoptotic effect. A significant (P = 0.03) reduction in the pre-G1 peak equivalent to an antiapoptotic response was observed in 6 of 13 cell cultures maintained in a SH-deficient environment. In 4 of 10 cell cultures evaluated in both media, the pre-G1 population was medium dependent. In 8 of 10 cultures evaluated for Bcl2 levels, no trend was found in either media, but a dependency on SH content was observed. Comparison between effects of TAM and estradiol demonstrated identical trends, regardless of the menstrual phase or SH content in cell environments. These results suggest that TAM acts as an estrogen agonist on endometrial tissue in both environments. We conclude that TAM modulates apoptotic pathways in primary endometrial cell cultures. The SH content in the cell environment influences the apoptotic effect of TAM and determines the propensity for a cell to undergo apoptosis or, on the contrary, to resist apoptotic death in response to TAM treatment. This is in concordance with the observed clinical risk of endometrial pathologies in postmenopausal versus premenopausal women.

A new mutation, I1307K, recently was reported in the adenomatous polyposis coli (APC) gene. This mutation was found to be predominant in Ashkenazi Jews, creating a hypermutable area and predisposing the development of carcinoma. The objective of the current study was to estimate the prevalence of this mutation in several of the ethnic groups that comprise the Israeli population and to elucidate the clinical features of the mutation carriers with colorectal carcinoma (CRC).A total of 111 consecutive CRC patients were evaluated and their medical history and clinical data recorded. The general population (298 Ashkenazim and 189 Yemenites) also was tested for the presence of this mutation. Mutation screening was performed using both the polymerase chain reaction-based amplification refractory mutation system and a commercial APC kit.Of the total of 111 CRC patients, 15 (13.5%) carried the I1307K mutation and 26 of 487 subjects from the general population (5.3%) carried the I1307K mutation (P = 0.004). Among the 71 Ashkenazi CRC patients there were 12 carriers (16.9%) whereas 17 of the 298 Ashkenazi Jewish general population (5.7%) carried the mutation (P = 0.004). Of the 4 CRC patients of Yemenite origin, 3 carried the mutation and 9 carriers were found among 189 subjects in the general Yemenite population (4.7%) (P = 0.0007). None of the 34 Sepharadic or 2 Arab CRC patients carried the APC I1307K allele. Late age at diagnosis (64.6 years +/- 10.0, which is similar to that of the noncarriers), mostly right-sided tumors, and moderate to good differentiation constituted the phenotype of the mutation carriers.The authors believe the findings of the current study broaden the known spectrum of ethnic groups in which the APC I1307K mutation is prevalent. The phenotype of the mutation carrier CRC patients does not conform to the expected familial pattern of germline mutations. The phenotype and the differential incidence rate of CRC among APC I1307K carriers of various ethnic groups suggest low penetrance.

A series of excellent articles published recently in Gut have evaluated the role of T regulatory (Treg) cells in inflammatory bowel disease (IBD) and surrogate animal models.1 2 In principle, self-tolerance in autoimmune disorders may be restored either by specific interference with effector cells and molecular pathways involved in immune activation, or selective enhancement of suppressive cells and cytokines. Based on the long-standing recognition that interleukin 2 (IL2) is a significant stimulatory cytokine involved in immune activation, interference with IL2 signalling has been considered as a potential approach to arrest autoimmunity. Stimulated lymphocytes (B and cytotoxic T cells) secrete IL2 and express the IL2 receptor α chain (CD25) within a positive feedback loop of activation. More physiological approaches to reinstitution of self-tolerance surround the activity of suppressive immune cells, in particular, Treg cells, which prevent and even reverse ongoing autoimmune reactions.3 4 5 6 One particular potent subset of naturally occurring Treg cells is characterised by CD25 expression at high levels in conjunction with transcription factor X-linked forkhead/winged helix (FoxP3). It is not only a contextual relationship between CD25 and suppressive mechanisms, but ample supply of IL2 is essential to the development and function of these Treg cells, and inhibition of IL2 production by cytotoxic cells is one of the primary mechanisms of suppression. Therefore, disruption of IL2 signalling that tilts the equilibrium against suppressive elements evolves as a deleterious mechanism in the context of autoimmunity, rather than an immunosuppressive strategy. Consistently, mice deficient in IL2 …

The putative oncogenes BCL-1, BCL-2, and BCL-3 are commonly rearranged by translocations to the immunoglobulin genes in B-cell malignancies. However, Southern blotting rarely detected their involvement in chronic lymphocytic leukemia (CLL). This discrepancy could stem from some unique features of the oncogenesis of CLL or be due to shortcomings of Southern blotting. We have therefore evaluated the role of fluorescence in situ hybridization (FISH) in the detection of these oncogenes in CLL. Twenty consecutive CLL patients were studied by FISH for the detection of BCL-1, BCL-2, or BCL-3 rearrangement and for the presence of trisomy 12. Selected patients were also evaluated by classical cytogenetic techniques and by Southern blot analysis. Juxtaposition of JH and BCL-1 was demonstrated in 10 (50%), BCL-2 in three (15%), and BCL-3 in four (20%) of the patients. Trisomy 12 was detected by FISH in 11 (55%) patients. The coexistence of trisomy 12 and translocation of the BCL-1 oncogene was common. Three of the patients had chromosomal aberrations compatible with those detected by FISH. In contrast, in none of the five patients selected by their positive FISH findings was a rearrangement demonstrated by Southern blotting. We conclude that FISH is a sensitive method for the detection of oncogene involvement in CLL. Mainly BCL-1, but also BCL-2 and BCL-3, are commonly translocated to the immunoglobulin heavy chain locus on chromosome 14. These translocations are often associated with trisomy 12. These findings indicate that the BCL oncogenes are commonly involved in CLL and lend support to the multi-hit theory of cancer development.

We examined the effect of norsegoline, a natural marine product, and dibezine, a synthetic product, on the survival of human myeloid progenitor cells [colony-forming unit-cells (CFU-C)] from normal individuals and from 10 patients with Philadelphia-positive chronic myelogenous leukemia (CML) in chronic phase and blastic crisis. We compared their effect to the effect of IFN-alpha. Norsegoline, dibezine, and IFN-alpha inhibited the proliferation of CFU-C in a dose-dependent manner. The number of CFU-C from bone marrow (BM) of five CML patients in chronic phase exposed for 16 h to norsegoline (10(-8)-10(-6)M), dibezine (10(-8)-10(-6)M), and IFN-alpha (500 units/ml) was found to be statistically lower (P0.05) than the number of CFU-C derived from normal individuals. A 16-h drug exposure of CD34(+) cells isolated from the peripheral blood of three CML patients in blastic crisis and from BM of two patients in chronic phase resulted in a marked inhibition in the ability of the cells to proliferate in liquid culture and a reduction in CFU-C content. Using the fluorescent in situ hybridization technique, we evaluated detection of the BCR/ABL fusion product in the CD34(+) cells. All five patients were 100% Philadelphia positive at diagnosis. BCR/ABL translocations were detected in 94.6 +/- 0.6% of cells following their growth in liquid culture for 7 days. Following exposure of CD34(+) cells to norsegoline, dibezine, or IFN-alpha, BCR/ABL fusion signals could be detected in 73 +/- 11%, 66.5 +/- 4. 7%, and 66.0 +/- 2.5% of cells from BM and 72.3 +/- 5%, 68.8 +/- 7%, and 60.6 +/- 6.8% of peripheral blood, respectively. Our data indicate that norsegoline and dibezine have in vitro an antileukemic effect against Philadelphia-positive cells and may be used in conjunction with currently available agents for ex vivo purging of BM and/or peripheral blood of CML patients in conjunction with autologous bone marrow transplantation.

Data concerning oncogene activation in CLL are very limited. When studied by Southern blot, rearrangements of bcl -1, bcl -2, and bcl -3 have been only infrequently reported. We evaluated the role of fluorescence in situ hybridization (FISH) in the detection of gene rearrangements in two CLL patients. We used multiple DNA probes, including those of chromosome 12, immunoglobulin heavy and light chains, and the oncogenes bcl -1, bcl -2, and bcl -3. Additionally, routine cytogenetic study was performed. In one patient, trisomy 12 and bcl -2 translocation were demonstrated by both methods, while trisomy 12 and bcl -1 translocation were seen in the second patient, who had a normal karyotype. Larger studies should evaluate the role of FISH in the detection of oncogene involvement in CLL and compare it with other molecular methods.

Burkitt's lymphoma cells exhibit the reciprocal balanced chromosomal translocation t(8:14) in 75% of patients. Cytogenetic analysis is time-consuming, requires in vitro culture with mitogens and enables to analyse a relatively small number of cells. We evaluated the role of multicolor fluorescent in situ hybridization (FISH) in the rapid detection of t(8:14) in Burkitt's lymphoma cells. FISH detected the JH/myc translocation in 100% of the cells of five cell lines carrying the classical t(8:14) and in fresh cells obtained from a newly diagnosed Burkitt's lymphoma patient. In contrast, the translocation was not detected in the Bajb cell line that does not carry t(8:14). We conclude that FISH is a rapid and reliable diagnostic tool for the detection of the JH/myc translocation in Burkitt's lymphoma patients.

Since the available data on growth in twin gestations have been derived from retrospective cross-sectional studies with varying results, a prospective longitudinal study was initiated to assess fetal head growth in twin gestations as compared to singleton pregnancies. In uncomplicated twin gestations, growth of the fetal head, based on the increment in growth over time and the rate of growth throughout pregnancy, was found not to be significantly different than in singleton pregnancies. In light of these findings, current nomograms derived from measurements obtained in singleton pregnancies remain useful for evaluating fetal head growth in twin gestations.

A case of congenital pyruvate kinase deficiency manifested at antenatal ultrasound as isolated hepatosplenomegaly is reported and the differential diagnosis is discussed. An aggressive obstetric management and appropriate neonatal care permitted a favorable neonatal outcome.

4757 Background: Halofuginone hydrobromide (Tempostatin) is an orally bioavailable quinazolinone derivative that acts as a signal transduction inhibitor in stromal cells and susceptible tumor cells...

Normal values for fetal spleen dimensions are proposed, including longitudinal, coronal, and transverse diameters, the perimeter, and the estimated volume. Similar values were then obtained in cases of Rh-immunization and prolonged premature rupture of the membranes. A good correlation between amniotic fluid optical density and fetal spleen size was found. Only severely affected fetuses showed splenic values above the upper limit. Since sonographic examination can be regarded as a reliable method, nomograms can be useful in detecting growth disorders of the fetal spleen and thus provide a new complementary method to identify possible fetal diseases of genetic disorders.

This communication examines the diagnostic value of the leukocyte esterase activity (LEA) test in the detection of intra-amniotic infection. Amniotic fluid from 171 consecutive patients with premature rupture of membranes (n = 149) and preterm labor (n = 22) was obtained through amniocentesis. Gram stain, bacterial and mycoplasma cultures, and LEA tests were performed. The LEA had a sensitivity of 19%, a specificity of 86.7%, a positive predictive value (PPV) of 42.3% and a negative predictive value (NPV) of 67.6% in the prediction of a positive amniotic fluid culture (prevalence of positive cultures = 33.9%). The Gram stain had a sensitivity of 36.2%, specificity of 94.7%, PPV of 77.8%, and NPV of 74.3%. When both tests were combined, a significant increase in sensitivity to 50% was observed. This was associated with a drop in specificity to 81.4%. There was a correlation between the number of white blood cells in the amniotic fluid and the result of the LEA test. A positive LEA assay was associated with an increased likelihood of postpartum endometritis, but not with clinical chorioamnionitis or neonatal infectious morbidity.

Fetal clavicular length was measured sonographically in 85 fetuses with gestational ages ranging from 15 to 40 weeks. Biparietal diameter (BPD) and femur length (FL) were also measured. A linear correlation was found between clavicular length and gestational age (coefficient of correlation = 0.81). A simple relation was found: The gestational age in weeks is approximately equal to the length of the clavicle as expressed in millimeters. The measurement of clavicular length can be a useful parameter for the estimation of gestational age and in the detection of congenital anomalies that affect the clavicles. Clavicular measurements may also prove useful in the detection of macrosomic fetuses at high risk for obstructed labor or shoulder dystocia.

SummaryIntra-uterine growth retardation may be classified by ultrasonography into symmetrical and asymmetrical. In the symmetrical type the biparietal diameter increases in parallel with, but below, the normal growth curve and the head to abdominal circumference ratio is normal. In the asymmetrical group the biparietal diameter is either normal or flattened, and deviates from the normal curve, whilst the head to abdomen circumference ratio is above normal in both situations. We have reviewed 34 cases of intra–uterine growth retarded fetuses. Ten of these were symmetrical of which five had malformations. Twenty-four were asymmetrical and in eighteen of them the mother had hypertensive disease. The course and outcome of pregnancy and labour were different in these two groups. This classification can be useful in planning the clinical management of pregnancies with fetal growth retardation.

A 25-year-old woman in the 7th month of pregnancy was operated upon for a ruptured cerebral aneurysm. Sodium nitroprusside was used to achieve effective controlled hypotension. Signs of foetal distress were transient. Subsequent delivery was spontaneous and uneventful. Development of the child at 2 yr was satisfactory. The various physiological aspects and the action of nitroprusside on both mother and foetus are discussed.

The value of real time ultrasonography (RTUS) in the management of first trimester elective pregnancy terminations was studied in 120 consecutive patients. RTUS was found essential in determining accurate gestational ages, identifying incomplete pregnancy terminations, diagnosing abnormal pregnancies, and in performing difficult terminations. It is suggested that RTUS be employed in the routine management of first trimester pregnancy terminations.

In vitro fertilization (IVF) and embryo transfer (ET) have recently become an accepted treatment modality for patients with mechanically caused infertility. The first series admitted to our program comprised 42 patients with confirmed mechanical infertility. The method of patient selection and the techniques of laparoscopy, follicular aspiration and oocyte recovery are described. From 26 laparoscopies, a total of 39 oocytes was recovered. Normal cleavage of 10 oocytes was obtained; they were transferred into the uterus at the 4- to 16-cell stage. One pregnancy was obtained. An IVF and ET program involves certain ethical, legal and religious questions, which have special implications in Israel: foster mothers and the use of donor sperm are forbidden. Only married couples may enter the program. Indications, methods, success rates and method failure are discussed.

Fetal stomach dimensions were measured sonographically in 152 fetuses with gestational ages ranging from nine to 40 weeks. Nomograms of the mean +/- 2 standard deviations (SD) for the longitudinal, anteroposterior, and transverse diameters of the fetal stomach were generated throughout pregnancy. A linear growth function was observed across gestational age, and a high degree of correlation existed between gestational age and the transverse (r = 0.809, P less than .0001), anteroposterior (r = 0.798, P less than .0001), and longitudinal (r = 0.749, P less than .0001) diameters. These data provide a method by which variations from the norm can be assessed, and offer potential prenatal diagnosis of a variety of gastrointestinal lesions.

The association between fetal heart rate (FHR) accelerations and fetal movements during uterine contractions was studied in 52 pregnant women near term or at the beginning of labor. FHR and uterine contractions were recorded by tococardiograph. At the same time, fetal movements, whether associated or not with contractions, were viewed by real-time ultrasound. During uterine contractions, 95.5% of the FHR accelerations were associated with fetal movements. Also, 90.9% of the accelerations which appeared when the uterus was not contracting were associated with fetal movements. Fetal movements were not seen in 91% of uterine contractions which were not associated with FHR accelerations. The suggestion is made that uterine contractions stimulate both fetal movements and FHR accelerations.

Indomethacin, a prostaglandin synthetase inhibitor given to 94 women suffering from functional menorrhagia, IUD's and sub mucous fibroid related bleeding, reduced menstrual loss and duration of menstruation in 70 patients (74.5 percent). A significant decrease in duration of menstruation of 2.1 days was obtained in the responding group. In functional bleeding, the mean decrease was 1.7 days, in IUD's related menorrhagia 2.9 days and in menorrhagia due to submucous fibroids 2 days. Age, parity and duration of menstruation before treatment had no significant effect on the response or reduction of duration of bleeding. The medication was discontinued only in two patients because of minor gastronntestinal symptoms.

Five quintuplet pregnancies, following induction of ovulation with clomiphene and HMG-HCG, are the subject of this communication. In 3 women, pregnancy was associated with ovarian overstimulation, and two patients required emergency surgery because of torsion of an ovarian cyst. Two women aborted in mid-trimester, while the other 3 delivered by cesarean section at 33-35 wk gestation. 15 babies were born, weighing 700-2200 g. 8 infants suffered from respiratory distress syndrome and 5 babies were born with correctable malformations. 13 newborns survived, and all are mentally and physically well-developed. Four of the 5 women conceived again. The management of the patients during multiple gestation and the outcome of pregnancy are discussed.

The Ypsilon intrauterine device (IUD), which consists of stainless steel covered with silicone rubber, was studied in 209 women. In the 3,169 woman-months of use, there were 21 pregnancies, nine expulsions, and in 24 instances the Ypsilon IUD was removed for medical reasons (side effects). The net cumulative pregnancy rate in the 12 months after insertion was 6.4% and the expulsion rate was 3.8%; the medical removal rate was 9.0%. No perforations or tubal pregnancies occurred. The comparatively low medical removal rate renders the Ypsilon IUD a fairly good device for clinical use, although the pregnancy rate is rather high.

Our experience with the New Anderson-Ansell “Latex Leaf” IUD is presented. This device is elastic, soft, made from inert silicone rubber and impregnated with copper and zinc. The elasticity allows easy insertion and removal, at reduced pain. The IUD was inserted in 185 women comprising 2376 months of use. The net cumulative termination rates for 12 months after insertion (life table method) are: for pregnancies 1.1%, for expulsion 3.8%, and for medical removal because of bleeding 27.0%. No perforations and no tubal pregnancies occurred.

The presence of HCG (human chorionic gonadotropin) in the blood and urine of women with IUDs during the luteal phase of the menstrual cycle has been reported and suggests that IUDs have a post-implantation abortifacient action (the embryo produces HCG after implantation). This study examines the validity of this hypothesis. 8 randomly selected Lippes Loop wearers aged 21 to 35 years (mean age, 29 years) participated in the study. IUD use ranged from 7 to 38 months (means, 23 months). Mean length of menstrual cycle was 30.5 days. The women were asked to have sexual intercourse regularly at least every 2 days, beginning from the 12th day of the menstrual cycle. 57 blood samples were collected every 2nd day, starting day 18 of the menstrual cycle until the onset of subsequent menses. Radioimmunoassay (RIA) for HCG beta subunit, luteinizing hormone (LH) and progesterone was done. Ovulation occured in all women as shown by serum progesterone levels above 3 mg/ml. HCG could not be detected in any sample, including samples with high levels of LH, suggesting that there is no cross-reactivity of the anti-HCG beta subunit antibody with LH. This study did not confirm studies of others which found HCG in the blood/urine samples of IUD wearers. The disparity in findings may be attributed to either non-specific interference, or of a cross-reaction between the anti-serum used for the beta HCG RIA and LH. The true mechanism of IUD remains unknown. Either the IUD prevents the embryo from reaching the HCG-secreting stage, or the IUD interferes with fertilization itself.

We present a 31-year-old woman with a 45,X chromosome constitution who had had two miscarriages. This report brings to 11 the number of presumably non-mosaic Ullrich-Turner syndrome patients who have achieved pregnancy. A review of the literature indicates an increased incidence of chromosome abnormalities and a high rate of fetal death in offspring of such patients. However, in light of the fertility in these patients, genetic counseling should be reevaluated and perhaps amniocentesis recommended in successful pregnancies.

To determine the relative accuracy of fetal weight estimation using the biparietal diameter (BPD), the abdominal circumference (AC), and the femur length (FL) in three formulae (BPD/AC, FL/AC, and BPD/AC/FL), 63 patients in labor were examined. All patients delivered within 24 hours of ultrasound examination. A good correlation was found between the estimated fetal weight and the actual birth weight, using the three formulae: BPD/AC (r = 0.96); FL/AC (r = 0.95); and BPD/AC/FL (r = 0.96). The FL/AC formula overestimated fetal weight (P less than 0.01), however, particularly in fetuses weighing more than 2000 g. The mean percentage error with the BPD/AC formula was 0.99 per cent, 3.82 per cent with the FL/AC, and 2.43 per cent with the BPD/AC/FL formula. This study showed that although all three formulae were comparable, the best estimation of the birth weight was obtained when either the BPD/AC or the BPD/AC/FL formulae were used. Additionally, the results demonstrate that reliable estimates of fetal weight can be made even at term or in laboring patients.

A 25-year-old woman in the 7th month of pregnancy was operated upon for a ruptured cerebral aneurysm. Sodium nitroprusside was used to achieve effective controlled hypotension. Signs of foetal distress were transient. Subsequent delivery was spontaneous and uneventful. Development of the child at 2 yr was satisfactory. The various physiological aspects and the action of nitroprusside on both mother and foetus are discussed.

A prospective longitudinal study was conducted in order to determine by sonographically estimated fetal weight the patterns of fetal growth in twins. Thirty-five healthy women with normal twin pregnancies were examined every three weeks from the 15th week of gestation to delivery. Among the measurements obtained were the biparietal diameter (BPD), the abdominal circumference, and the calculated fetal weight. From 15-28 weeks, the growth velocity of the BPD and abdominal circumference remained fairly constant, with a steady increase in incremental growth. Beyond this age, we observed a slowing in growth of the BPD, while the abdominal circumference continued at a constant rate. The growth velocity of the weight steadily increased throughout pregnancy. Although greater biologic variability in weight between twin A and B was observed as gestational age progressed, the overall mean weights of twin A and B were not statistically different. We have generated a nomogram of fetal weight gain throughout pregnancy.

Fetal activity throughout pregnancy has been thoroughly studied. Relatively little informations regarding intrapartum fetal activity is available. Richardson et al. [8] found no fetal respiratory movements. While Boylan et al. [2] and Whittman et al. [12] reported decreased fetal breathing movements in active labor. This study was undertaken to evaluate the normal pattern of fetal activity in labor. Fetal movements (FM) and fetal breathing movements (FBM) were monitored by realtime ultrasound during active labor at term. The incidence of FM and FBM were measured in 18 fetuses. Results were correlated with simultaneous fetal heart rate (FHR) changes, postpartum cord blood pH and Apgar score. Recordings were made for one hour on every patient. The mean percentage incidence (PI) of FM was 19.5 per cent (range: 10.1-28.6 percent) and FBM was 8.5 per cent (range: 0-27 percent). All FM were associated with FHR accelerations, stronger movements were associated with higher FHR accelerations. No FHR accelerations were observed with FBM alone, unless accompanied by fetal movement. The lowest PI of total fetal activity (TFA, i.e. FM plus FBM) was 12.1 per cent. Movements decreased as labor progressed, while FBM remained unaltered. All newborns had cord venous blood pH of greater than 7.25 and Apgar scores of greater than or equal to 7, at five minutes. Our data suggest that in the normal uncompromised fetus, FM and FBM continue during labor at term. However, while FM tends to decrease as labor progresses. FBM tends to be constant throughout labor. This finding might indicate the autonomous nature of FBM.(ABSTRACT TRUNCATED AT 250 WORDS)

The development of fetoscopy and the ability to obtain fetal blood samples have made possible the prenatal diagnosis of diseases not diagnosable by amniocentesis. Foremost among these disorders are the hemoglobinopathies. We report our experience in establishing the first program for fetoscopy and fetal blood sampling in the Middle East. The results demonstrate that the experience and training required for a fetoscopy and fetal blood sampling program can be obtained in about one year. During that year, 23 couples who fetuses were at risk for a hemoglobinopathy learned the genetic status of their fetuses.

A case of hyperprolactinemic anovulation with amenorrhea and galactorrhea, due to Phenothizine derivative (Majeptil) is presented. Treatment with bromocriptine, 2.5 mg b.i.d., p.o., or L-Dopa, 500 mg, p.o., did not suppress serum prolactin and menstrual cycle was not resumed. Pituitary prolactin response to TRH and Pituitary LH and FSH response to LHRH were found to be normal. It seems that at the dose used, bromocriptine (a dopaminergic agonist) cannot counteract the phenothiazine induced hyperprolactinemia. Hence, it is not effective in induction of ovulation while the patient is under phenothiazine treatment.