Can foam sclerotherapy be used to safely treat bilateral varicose veins?

OBJECTIVE: We assessed the use of ultrasound guided foam sclerotherapy (UGFS) to treat bilateral varicose veins either as synchronous or interval procedures. We specifically assessed total foam volume usage and its influence on early outcome and complications. METHODS: We reviewed our prospectively compiled computerised database of patients with bilateral varicose veins who have undergone UGFS. Duplex findings, foam volumes used and clinical outcome were assessed. RESULTS: One hundred and twelve patients had undergone UGFS for bilateral varicose veins. Sixty-one had bilateral UGFS (122 legs) and 51 had interval UGFS (102 legs). Seventy-eight percent bilateral and 60% interval procedures were for single trunk disease. Median foam volumes per treatment episode were: 17.5 mls bilateral, and 10 mls interval FS. At two weeks 81% of legs had complete occlusion after bilateral UGFS compared to 70% after interval UGFS. One patient in the bilateral UGFS developed transient visual disturbance. There was no systemic complications in the interval UGFS. CONCLUSIONS: Bilateral foam sclerotherapy treatment did not adversly affect vein occlusion rates and there was no significant difference in complication rates between the two groups. Bilateral UGFS can be safely performed in selected patient presenting with bilateral varicose veins.

Isocostunolide, a sesquiterpene lactone, induces mitochondrial membrane depolarization and caspase-dependent apoptosis in human melanoma cells.

Isocostunolide is a sesquiterpene lactone isolated from the roots of Inula helenium. Its chemical structure was determined by NMR and FAB-MS spectra. No biological activities of this compound have yet been reported. In this study, we found isocostunolide could effectively induce cytotoxicity in three cancer cell lines (A2058, HT-29, and HepG2), with an IC(50) of 3.2, 5.0, and 2.0 micro g/mL, respectively. DNA flow cytometric analysis indicated that isocostunolide actively induced apoptosis of cancer cells accompanied by a marked loss of G0/G1 phase cells. To address the mechanism of the apoptotic effect of isocostunolide, we analyzed the induction of apoptosis-related proteins in A2058. The levels of pro-caspase-8, Bid, pro-caspase-3, and poly(ADP-ribose) polymerase (PARP) decreased. However, the level of Fas was increased markedly in a dose-dependent manner. Furthermore, this compound markedly induced a depolarization of mitochondrial membranes to facilitate cytochrome c release into cytosol. The findings suggest that isocostunolide may activate a mitochondria-mediated apoptosis pathway. To address this, we found that isocostunolide-induced loss of mitochondrial membrane potential occurred via modulation of the Bcl-2 family proteins. The production of intracellular reactive oxygen species (ROS) in A2058 was not elicited. In summary, for the first time, we have isolated and characterized isocostunolide from I. helenium. This compound induces apoptosis through a mitochondria-dependent pathway in A2058 cells.

Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3'-digallate (TF3).

SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS). The virally encoded 3C-like protease (3CL(Pro)) has been presumed critical for the viral replication of SARS-CoV in infected host cells. In this study, we screened a natural product library consisting of 720 compounds for inhibitory activity against 3CL(Pro). Two compounds in the library were found to be inhibitive: tannic acid (IC(50) = 3 microM) and 3-isotheaflavin-3-gallate (TF2B) (IC(50) = 7 microM). These two compounds belong to a group of natural polyphenols found in tea. We further investigated the 3CL(Pro)-inhibitory activity of extracts from several different types of teas, including green tea, oolong tea, Puer tea and black tea. Our results indicated that extracts from Puer and black tea were more potent than that from green or oolong teas in their inhibitory activities against 3CL(Pro). Several other known compositions in teas were also evaluated for their activities in inhibiting 3CL(Pro). We found that caffeine, (-)-epigallocatechin gallte (EGCg), epicatechin (EC), theophylline (TP), catechin (C), epicatechin gallate (ECg) and epigallocatechin (EGC) did not inhibit 3CL(Pro) activity. Only theaflavin-3,3'-digallate (TF3) was found to be a 3CL(Pro) inhibitor. This study has resulted in the identification of new compounds that are effective 3CL(Pro) inhibitors.

Evaluation of metal-conjugated compounds as inhibitors of 3CL protease of SARS-CoV.

3C-like (3CL) protease is essential for the life cycle of severe acute respiratory syndrome-coronavirus (SARS-CoV) and therefore represents a key anti-viral target. A compound library consisting of 960 commercially available drugs and biologically active substances was screened for inhibition of SARS-CoV 3CL protease. Potent inhibition was achieved using the mercury-containing compounds thimerosal and phenylmercuric acetate, as well as hexachlorophene. As well, 1-10 microM of each compound inhibited viral replication in Vero E6 cell culture. Detailed mechanism studies using a fluorescence-based protease assay demonstrated that the three compounds acted as competitive inhibitors (Ki=0.7, 2.4, and 13.7 microM for phenylmercuric acetate, thimerosal, and hexachlorophene, respectively). A panel of metal ions including Zn2+ and its conjugates were then evaluated for their anti-3CL protease activities. Inhibition was more pronounced using a zinc-conjugated compound (1-hydroxypyridine-2-thione zinc; Ki=0.17 microM) than using the ion alone (Ki=1.1 microM).

Cloning, functional expression, and characterization of cystatin in sesame seed.

A cDNA fragment encoding cystatin, a cysteine protease inhibitor, was obtained from maturing sesame seeds. The clone was constructed in a nonfusion or fusion vector and then overexpressed in Escherichia coli. The recombinant cystatins were found in the soluble fraction of cell extract and were demonstrated to be functionally active in a reverse zymographic assay. The corresponding endogenous 22 kDa cystatin of low abundance in mature seeds was purified to homogeneity via a papain-coupling affinity column and confirmed by western blotting with antibodies against the recombinant cystatin. Both endogenous and recombinant cystatin proteins showed effective inhibitory activities against papain with K(i) values of 7.89 x 10(-8) M and 2.77 x 10(-8) M, respectively. Immunodetection indicated that cystatin was specifically expressed in maturing seeds and rapidly degraded in germination. Accordingly, zymographic and inhibition analyses showed that sesame cystatin could not inhibit the de novo synthesized proteases in germinating seeds. It is suggested that sesame cystatin may play a role in the regulation of endogenous cysteine proteases during seed maturation and germination.

Effects of hormone replacement therapy on olfactory sensitivity: cross-sectional and longitudinal studies.

OBJECTIVE: To determine whether hormone replacement therapy (HRT) preserved or improved olfactory sensitivity in healthy postmenopausal women. METHODS: Sixty-two postmenopausal women participated in a cross-sectional study of olfactory sensitivity involving detection, intensity discrimination, quality discrimination and two measures of quality recognition. In addition, 24 postmenopausal women participated in a longitudinal study of olfactory sensitivity. This study allowed for the measurement of estrogen effects (while holding practice effects constant) and the measurement of practice effects (while holding HRT conditions constant). RESULTS: In the cross-sectional study, we were unable to detect any differences between those receiving HRT and those not receiving HRT. Duration of exposure to HRT was examined by selecting women who had 5 or more years of exposure to their HRT regimen. Even after the data were reorganized into those for opposed- and unopposed-estrogen use, we were unable to detect any differences. However, olfactory threshold increased as a function of increasing age, regardless of HRT status. A gradual decrease in ability to detect odors was observed from the 4th to the 6th decade, with a greater decrease between the 6th and 7th decades. In the longitudinal study, no effects of HRT were detected even when practice effects were uncontrolled. Practice effects were assessed both between and within subjects. No effects of practice were detected when initial baseline performance was used as a covariate. CONCLUSION: Although prophylactic HRT has been suggested to be associated with improved olfactory function, we find that its use in healthy postmenopausal women does not enhance performance in a wide range of olfactory tasks.

Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials.

Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives (OCs) containing 20 microg ethinyl estradiol (EE) have not been demonstrated in placebo-controlled trials. Two placebo-controlled, randomized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females (n = 704; >or=14 years old) with regular menstrual cycles and moderate facial acne. Patients were randomized to receive 20 microg EE/100 microg levonorgestrel (LNG) or placebo for six cycles. Body weight was measured at baseline and during Cycles 1, 3, and 6. The occurrence of adverse events was recorded at each visit. Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [0.72 kg +/- 2.64 (SD; n = 349)] and placebo [0.56 kg +/- 2.64 (SD; n = 355; p > 0.05)] for the last measured weight of each patient. Rates of headache, nausea, weight gain, and breast pain, side effects commonly attributed to OCs, were also similar between groups (p > 0.05). No serious, unexpected, drug-related adverse events occurred during the study. The low-dose OC containing 20 microg EE/100 microg LNG is safe, well tolerated, and does not cause weight gain.

The effects on ovarian activity of a monophasic oral contraceptive with 100 microg levonorgestrel and 20 microg ethinyl estradiol.

An open-label, single-center, noncomparative study was conducted to determine the effects of a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol on ovarian activity. The subjects were 26 healthy women 20 to 35 years of age who had normal ovulatory cycles and were not at risk for becoming pregnant. For 3 treatment cycles, they took 1 tablet of active drug daily for 21 days followed by placebo tablets for 7 days. Follicle diameters and serum progesterone and 17beta-estradiol levels were measured before, during, and after treatment. In 2 (2.7%) of 73 cycles, luteinized unruptured follicles were present and in another 2 (2.7%) cycles, ovulation was confirmed by the disappearance of the enlarged follicle. Ovarian activity, as reflected by mean serum progesterone levels, was restored after treatment. The results of this study are in agreement with those of other studies that showed suppression of ovarian activity in women treated with a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. These results indicate that low-dose 100 microg levonorgestrel and 20 microg ethinyl estradiol given for 21 days is effective in suppressing ovarian activity and they confirm the contraceptive efficacy observed in clinical trials (Pearl index of 0.8).

Inhibin-A and pro-alpha C are elevated in preeclamptic pregnancy and correlate with human chorionic gonadotropin.

PROBLEM: Serum concentrations of the heterodimeric glycoprotein inhibin-A (alpha-beta A) and its alpha-subunit increase during pregnancy. The placenta is the predominant source of inhibin during pregnancy, and a paracrine role in the trophoblast has been suggested. Elevated serum concentrations of inhibin alpha-subunit as well as the glycoprotein human chorionic gonadotropin (hCG) have been described in preeclamptic pregnancy. The objectives of this investigation were to compare serum concentrations of inhibin-A and inhibin pro-alpha C in preeclamptic and normotensive pregnancy, and to examine the relationship of hCG and inhibin-A in those pregnancies. METHOD OF STUDY: A case-control design using 32 patients with preeclampsia with a single fetus at 32-40 weeks of gestation and 34 gestation age-matched normotensive control subjects was used for this investigation. Solid-phase enzyme-linked immunosorbent assays were used to measure inhibin-A and inhibin pro-alpha C in sera. An immunoradiometric assay was used to measure intact hCG. RESULTS: Inhibin-A and inhibin pro-alpha C concentrations were significantly elevated in the sera of women with preeclampsia compared with those concentrations in normotensive control subjects (P < 0.05). A relationship of inhibin-A or pro-alpha C with severity of preeclampsia was not observed. There was a significant positive correlation of serum hCG with both inhibin-A and pro-alpha C (P < 0.05). CONCLUSIONS: Levels of inhibin-A and the subunit pro-alpha C are increased in pregnancies complicated by preeclampsia. These findings are potentially the effect of a paracrine role of inhibin-A in the development and proliferation of the trophoblast.

Systemic lupus erythematosus in pregnancy.

Systemic lupus erythematosus is an inflammatory autoimmune disease that can affect multiple organ systems. The most popular theory regarding the origin of its clinical manifestations is that autoantibodies and circulating immune complexes become trapped in the capillaries of visceral structures.

Platelet and hemorrhagic disorders associated with pregnancy: a review. Part I.

Disorders of coagulation remain an important potential cause of maternal morbidity and mortality. Bleeding disorders in pregnancy, unlike disorders of hypercoagulability, most often can have little impact on the mother but devastating consequences for the fetus. Further complicating the issue is that not all disorders of coagulation are inherited. Some are due to maternal illnesses unique to pregnancy, others are due to drug ingestion, and yet others remain idiopathic. In still other instances, thrombocytopenia is a minor consequence of a more severe disorder and will resolve when the inciting agent is removed or treated. A basic understanding of the pathophysiology of various conditions that lead to bleeding diathesis in pregnancy is necessary in order to effectively manage these varied clinical disorders. In addition, knowledge of whether the major morbidity is fetal or maternal or both can impact management. This review is concerned with the etiology, pathophysiology, diagnosis, and general management of commonly encountered disorders in pregnancy that place the mother and fetus at increased morbidity and mortality because of the potential for hemorrhage. Acutely acquired disorders and the resultant maternal manifestation versus a chronic disease process that is altered by the state of pregnancy are distinguished. Where possible, the incidence and prognosis of the disorder are provided. Actual cases are included to illustrate how similar presentations of distinctly different disorders can confuse and complicate an accurate diagnosis that is essential for appropriate management.

Dithiothreitol effects on the viscosity and quality of human semen.

OBJECTIVE: To determine the effects of treatment with dithiothreitol (DTT) on seminal viscosity, consistency, and sperm motility, motion characteristics, and morphology. DESIGN: Prospective, in vitro study. SETTING: University teaching hospital. PATIENTS: Semen donors and patients of the infertility program. Experiment 1, n = 34; experiment 2, n = 82. Sufficient seminal volume for use was the only selection criterion. INTERVENTIONS: Experiment 1: semen was combined with 5.9 mM DTT solution 1:1 (vol/vol), combined with distilled water 1:1 (vol/vol), or untreated. Experiment 2: semen was combined with 5.9 mM DTT solution 1:1 (vol/vol) or untreated. MAIN OUTCOME MEASURES: Seminal consistency and viscosity, percentage of motile sperm, sperm motion characteristics (straight line velocity, curvilinear velocity, mean linearity, and angle of lateral head displacement), sperm concentration, and sperm morphology. RESULTS: Treatment of semen with DTT reduced seminal consistency and viscosity. Treatment with DTT had no effect on sperm concentration or percentage motile sperm. Sperm velocity was reduced by DTT treatment, particularly in semen that had normal initial consistency. Morphology of sperm in semen exhibiting abnormal initial consistency was unaffected by DTT. CONCLUSION: Dithiothreitol effectively induced liquefaction of nonliquefied semen in vitro and had minimal effects on the sperm motility, motion characteristics, and morphology. Evaluation of DTT effects on the chromatin and on other functional traits of human sperm must be conducted before its use can be advocated.

Ethanol has direct inhibitory effects on steroidogenesis in human granulosa cells: specific inhibition of LH action.

We have evaluated the direct effects of ethanol (EtOH) on the production of progesterone (P) and estradiol-17 beta (E2) by cultured human granulosa cells obtained during in vitro fertilization procedures. On day 3 of culture, cells were divided into control and ethanol (20 mM) groups and stimulated by hFSH (50 ng/ml), hLH (0-50 ng/ml), FSH+LH, 8 Br-cAMP (0.25 mM) and androstenedione (10(-7) M). Experiments were terminated on days 7 and 9 and DNA, P, and E2 were measured. Ethanol inhibited P and E2 secretion stimulated by LH; however, there was no significant effect of ethanol on P and E2 production in the control group or when the cells were stimulated by FSH or cAMP. EtOH also had no effect on androstenedione stimulated E2 production. There was no significant difference in the DNA contents of the human granulosa cells in the ethanol group as compared with the control group. These results are the first demonstration of a direct effect of ethanol on cultured granulosa-lutein cells and suggest that ethanol may inhibit action of LH on the corpus luteum. A direct selective toxic effect of EtOH on the ovary may be responsible for some of the reproductive abnormalities observed in alcoholic women.

Methods of ovulation induction.

The results of ovulation induction in patients with ovulatory dysfunction were reviewed for a one year period. Eighty-six women were assigned to four groups: secondary amenorrhea, anovulation, oligo-ovulation, and luteal phase defect/short luteal phase (LPD). All patients were monitored with basal body temperature (BBT) graph, postcoital testing, and ultrasonic scanning of ovarian follicles. All patients received therapy with clomiphene citrate (CC) for a minimum of four cycles and 13 patients conceived. Fifty patients were offered additional therapy with human menopausal gonadotropins (HMG-HCG). Seventeen completed a minimum of four cycles, and 13 conceived. The number of CC-treated patients with poor mucus quality in the face of adequate follicular development was 24, or 48%. The overwhelming problem with ovulation induction when CC failed was the large number of patients who dropped out of therapy, 48%. In summary, close monitoring during ovulation induction to confirm ovulation, and assess mucus quality and luteal function allow detection and correction of inadequate response. Induction of ovulation can be highly successful if patients can follow through and complete protocols of therapy.

Motility and fertilizing ability of rat epididymal spermatozoa washed by a continuous gradient of Percoll.

Removal of epididymal fluids from epididymal sperm suspension is an important step for the study of sperm motility, capacitation, and the acrosome reaction. The technique of washing should minimize damage to viable spermatozoa but at the same time efficiently remove debris, non-sperm cells, and biological fluids. We examined sperm motility and fertilizability in vitro of rat epididymal spermatozoa after washing with Percoll continuous gradient. Nine milliliters (ml) of 50% N-2-hydroxyethylpiperazine-N1-2-ethanesulfonic acid (HEPES) buffered Percoll solution was centrifuged at 20,000 g for 45 minutes to form a continuous gradient. One hundred to 300 microliters of sperm suspension was loaded onto the surface of the gradient and centrifuged at 150 g and 1,500 g for 10 minutes. Two main layers of spermatozoa were formed, one of high (lower layer) and one of low (upper layer) motility. At centrifugation 1,500 g, the sperm density and motility in the lower layer were greater than at 150 g. Spermatozoa from both layers at 150 g and at 1,500 g were diluted with modified Krebs-Ringer's bicarbonate solution (mKRB) and preincubated for 5 hours. Superovulated eggs collected from 21-25-day-old Wistar strain immature rats were introduced into the preincubated sperm suspension for insemination and fixed 5-5.5 hours later for observation of fertilization. Spermatozoa from both layers, 150 g and 1,500 g, showed the same fertilizability in vitro as control spermatozoa. From these results we conclude that Percoll gradients can be used for washing rat epididymal sperm for the study of sperm physiology including fertilization.

Effect of aromatase inhibitors on the histology of the cycling rat ovary.

Two aromatase inhibitors, 4-hydroxyandrostenedione (4-OHA) and testololactone (Teslac), were tested to determine their effects on folliculogenesis, particularly ovarian histologic alterations, in the cycling rat. Adult, female Sprague-Dawley rats were treated with continuous infusion of both inhibitors at concentrations of 10(-8), 10(-4), and 10(-2) M for 30 days. The effect of the inhibitors on cultured granulosa cells harvested on proestrus was determined in vitro. The in vivo administration of each inhibitor induced significant reduction in ovarian-vein estradiol levels. Estradiol synthesis in cultured granulosa cells was inhibited by both aromatase inhibitors in a dose-dependent fashion. These observations indicate that 4-OHA and Teslac significantly inhibit basal estradiol synthesis in vivo and in vitro. This effect on estrogen synthesis was not reflected in alteration of the ovarian histology in the cycling rat.

Cryosurgical treatment of early cervical intraepithelial neoplasia.

Two hundred forty patients, ages 12 to 54 years, with biopsy-confirmed early cervical intraepithelial neoplasia (CIN I) treated by cryosurgery were reviewed. CIN I has been viewed historically as having high rates of remission or stabilization. The initial cure rate was 89%, with a 97% cure rate after retreatment of failures. All failures were confirmed histologically. The initial cure rates are no better than those for higher grades of CIN. Thus, CIN I should be viewed with the same seriousness as CIN II or CIN III.