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PubMed1982

Comparison of DNA sequences required for the function of citrate utilization among different citrate utilization plasmids.

The relatedness of DNA sequences encoding citrate utilization was examined by hybridization with a cloned DNA fragment from a citrate utilization (Cit) plasmid, pOH30221, and DNA of other Cit plasmids. This revealed that there are at least two groups of Cit plasmids: the Inc W Cit plasmids, which show homology with the probe, and the Inc H1 plasmids, which do not.

Base Sequence↗
PubMed1981

Liquid preservation of baboon red blood cells in acid-citrate-dextrose or citrate-phosphate-dextrose anticoagulant: effects of washing liquid-stored red blood cells.

Autologous baboon RBC stored at 4 C in acid-citrate-dextrose (ACD) or in citrate-phosphate-dextrose (CPD) for 3 weeks after collection had 24-hour 51Cr posttransfusion survival values of about 77%. When 20-day-old ACD and CPD baboon RBC were washed and then stored at 4 C for 24 hours before autotransfusion, the 24-hour 51Cr posttransfusion survival values were about 81%. These values were similar to those seen in studies of human RBC preserved in an identical manner. Our results indicated that the baboon can be used to evaluate RBC preservation techniques before human volunteers are studied.

Animals↗
PubMed2004

[The use of clomiphene citrate in ambulatory medicine practice in the Midi-Pyrénées area: compliance to national guidelines applicable to infertility diagnosis and to prescription and monitoring rules applicable to clomiphene citrate treatments].

OBJECTIVE: Evaluate the compliance to the national guidelines from ANDEM (1996) and AFSSAPS (2003) concerning the diagnosis of infertility, the prescription of clomiphene and the monitoring of these treatments. PATIENTS AND METHODS: Retrospective study of female patients from 16 to 50 y.o. having benefited from reimbursement of clomiphene citrate treatment between 1st April 2002 and 30th June 2002. After random sampling stratified on age, data on diagnosis procedures and treatments were extracted from the Social Security reimbursement database. These data were validated and completed by patients' interviews. RESULTS: A total of 283 women were included. 30% were subject to the basic hormonal tests (FSH, LH, estradiol). The proportion of patients explored by hysterosalpingogram, post-coital test and echography were respectively 50%, 35% and 68%. A semen analysis was found in 60% of the partners. The complete set of recommended tests before start of treatment was realised in 1.5% of women. In 7% of cases, women were treated without prior exploration. The proportion of tests performed was comparable below and above the age of 35. 77% of treatments were initiated after at least one year of waiting for a spontaneous conception. 69% of women were monitored during treatment by other methods than clinical follow-up. CONCLUSION: Prescription of clomifene citrate is too frequently realised without compliance to guidelines applicable to infertility investigations and therefore without persuasive diagnosis. These practices can lead to loss of childbearing opportunities and complications.

Adult↗
PubMed2001

A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction.

OBJECTIVE: To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility. DESIGN: Prospective randomized trial. SETTING: Infertility clinic in a university teaching hospital. PATIENT(S): Eighty-six anovulatory women under 40 years of age undergoing ovulation induction. INTERVENTION(S): The women were assigned randomly to receive either TMX or CC on cycle days 5-9. MAIN OUTCOME MEASURE(S): Rates of ovulation and pregnancy for the two treatment modalities. RESULTS(S): The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group. CONCLUSION(S): The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility.

Adult↗
PubMed1993

A clomiphene citrate and tamoxifen citrate combination therapy: a novel therapy for ovulation induction.

OBJECTIVE: To assess the efficacy of a clomiphene citrate (CC) and tamoxifen citrate (CC/tamoxifen) combination therapy in ovulation induction by comparing with a CC alone therapy. DESIGN: A randomized cross-over study with CC alone and CC/tamoxifen combination therapies for 20 normoprolactinemic anovulatory women. Randomly selected 10 of the 20 women (group A) underwent a CC alone therapy (100 mg CC during cycle days 5 to 9) for the initial three consecutive treatment cycles and a CC/tamoxifen combination therapy (50 mg CC and 20 mg tamoxifen during cycle days 5 to 9) for the subsequent three consecutive treatment cycles. The remaining 10 (group B) were treated similarly but with the inverse sequence. Ovulation was documented when a high BBT phase persisted for 11 days or more, when midluteal serum P levels exceeded 7 ng/mL (22.3 nmol/L), or when pregnancy ensued. RESULTS: The rates of ovulatory/treated, pregnant/treated, and pregnant/ovulatory cycles were 42 of 56 (75.0%), 3 of 47 (6.4%), and 3 of 35 (8.6%) for CC/tamoxifen, respectively. Those were 25 of 57 (43.9%), 1 of 48 (2.1%), and 1 of 21 (4.8%) for CC, respectively. Clomiphene citrate/tamoxifen was more effective in ovulation induction than CC. All the pregnancies were normal and single. None of the treatments was accompanied by any remarkable side effects. CONCLUSION: Clomiphene citrate/tamoxifen is a novel treatment modality of ovulation induction with high efficacy.

Adult↗
PubMed2004

Management of anovulatory infertility associated with polycystic ovary syndrome: tamoxifen citrate an effective alternative compound to clomiphene citrate.

Clomiphene citrate (CC) is widely used as first-line treatment for ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS). Tamoxifen citrate (TMX), another non-steroidal selective estrogen receptor modulator, may also be effective on the resumption of ovulation in these women. The aim of this controlled observational study was to compare the efficacy and safety of ovulation induction with TMX versus CC in anovulatory infertile women with PCOS. A total of 102 consecutive women (mean age+/-SD: 31+/-3.6 years; range: 26-38) with PCOS were studied. Following a spontaneous or progesterone-induced withdrawal bleed, women received either 50 mg daily of CC (days 2-6) or 20 mg daily of TMX (days 2-5). In case ovulation failed to occur, the dose was sequentially increased to 100 mg daily of CC and 40 mg daily of TMX, respectively. Serum progesterone levels were measured on cycle day 21 to monitor the ovulation pattern. The overall ovulation rate was significantly higher in women who received TMX compared with those who received CC (61/98, 62.2% vs. 60/127, 47.2%, p=0.03). Although not statistically significant, the pregnancy rate per ovulatory cycle was higher in the TMX group compared to the CC group (14/61, 22.9% vs. 11/60, 18.3%, respectively). All pregnancies were single and there were no side-effects in either group of treatment. Collectively, these data demonstrate that TMX is a safe and effective agent, and a suitable alternative to CC for anovulatory infertility in women with PCOS.

Adult↗
PubMed2006

Clomiphene citrate and dexamethazone in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective placebo-controlled study.

BACKGROUND: The aim of this work was to evaluate the efficacy of adding dexamethazone (DEX) (high dose, short course) to clomiphene citrate (CC) in CC-resistant polycystic ovary syndrome (PCOS) with normal dehydroepiandrosterone sulphate (DHEAS) in induction of ovulation. METHODS: Eighty infertile women with CC-resistant PCOS were randomly assigned into two groups. Group I: Clomiphene citrate 100 mg/day was given from day 3 to day 7 of the cycle and DEX 2 mg/day from day 3 to day 12 of the cycle. Group II: Same protocol of CC combined with placebo (folic acid tablets) was given from day 3 to day 12 of the cycle. The main outcome was ovulation. Secondary measures included number of follicles >18 mm endometrial thickness and pregnancy rate. Ovarian follicular response was monitored by transvaginal ultrasound. HCG 10,000 U was given when at least one follicle measured 18 mm, and timed intercourse was advised. RESULTS: There were no statistically significant differences between groups as regards age, duration of infertility, BMI, waist-hip ratio (WHR), menstrual pattern, hirsutism, serum DHEAS or day of HCG administration. The mean number of follicles>18 mm at the time of HCG administration and the mean endometrial thickness were significantly higher in the DEX group than in the placebo group (P<0.05). Similarly, there were significantly higher rates of ovulation (75 versus 15%) (P<0.001) and pregnancy (40 versus 5%) (P<0.05) in the DEX group. Dexamethazone was very well tolerated as no patients complained of any side effect. There was a significant difference between the responders and non-responders in the presence of oligomenorrhea, amenorrhea or hirsutism. CONCLUSION: Induction of ovulation by adding DEX (high dose, short course) to CC in CC-resistant PCOS with normal DHEAS is associated with no adverse anti-estrogenic effect on the endometrium and higher ovulation and pregnancy rates in a significant number of patients. Induction with DEX appears to be independent on age, period of infertility, BMI or WHR.

Adult↗
PubMed2006

As a bacterial culture medium, citrated sheep blood agar is a practical alternative to citrated human blood agar in laboratories of developing countries.

Human blood agar (HuBA) is widely used in developing countries for the isolation of bacteria from clinical specimens. This study compared citrated sheep blood agar (CSBA) and HuBA with defibrinated horse blood agar and defibrinated sheep blood agar (DSBA) for the isolation and antibiotic susceptibility testing of reference and clinical strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus. Reference and clinical strains of all organisms were diluted in brain heart infusion and a clinical specimen of cerebrospinal fluid and cultured on all agars. Viable counts, colony morphology, and colony size were recorded. Susceptibility testing for S. pneumoniae and S. pyogenes was performed on defibrinated sheep blood Mueller-Hinton agar, citrated sheep blood Mueller-Hinton agar (CSB MHA), and human blood Mueller-Hinton agar plates. For all organisms, the colony numbers were similar on all agars. Substantially smaller colony sizes and absent or minimal hemolysis were noted on HuBA for all organisms. Antibiotic susceptibility results for S. pneumoniae were similar for the two sheep blood agars; however, larger zone sizes were displayed on HuBA, and quality control for the reference strain failed on HuBA. For S. pyogenes, larger zone sizes were demonstrated on HuBA and CSBA than on DSBA. Poor hemolysis made interpretation of the zone sizes difficult on HuBA. CSBA is an acceptable alternative for the isolation of these organisms. The characteristic morphology is not evident, and hemolysis is poor on HuBA; and so HuBA is not recommended for use for the isolation or the susceptibility testing of any of these organisms. CSB MHA may be suitable for use for the susceptibility testing of S. pneumoniae.

Agar↗
PubMed1976

Quantitative determination of piperazine citrate in piperazine citrate syrup USP.

An assay for piperazine citrate in Piperazine Citrate Syrup USP is described. The assay method is based on the formation of a complex of piperazine with an acid dye, bromothymol blue. The complex can be extracted with chloroform and measured spectrophotometrically. The method is accurate and requires only 15 minutes for analysis, compared to four to five hours by the USP method.

Hydrogen-Ion Concentration↗
PubMed1983

[Scintigraphy with 67Ga-citrate and 169Yb-citrate in the diagnosis of lung cancer].

A scintigraphic study was made of 44 lung cancer patients. At first the diagnosis was made on the basis of an x-ray finding, then it was specified with the help of radioisotope scintigraphy and fibrobronchoscopy with histological examination. 67Ga-citrate and 169Yb-citrate with the activity of 74 MBk were used i. v. for scintigraphy. The scanning was done 72 hrs. after the application of a radionuclide using the magnascanner Picker-500 (USA). In 88.3% of the cases positive scintigraphic results were confirmed histologically as a malignant lung process. A conclusion has been made that both radionuclides are suitable for tumorotropic lung scintigraphy. Owing to its potentialities they can substitute in certain cases for more traumatic roentgenobronchography that also gives radiation exposure.

Adult↗
PubMed2003

The mitochondrial citrate transport protein: probing the secondary structure of transmembrane domain III, identification of residues that likely comprise a portion of the citrate transport pathway, and development of a model for the putative TMDIII-TMDIII' interface.

The mitochondrial citrate transport protein (CTP) has been investigated by mutating 28 consecutive residues within transmembrane domain III (TMDIII), one at a time, to cysteine. A cysteine-less CTP that retains wild-type functional properties, served as the starting template. The single Cys CTP mutants were abundantly expressed in Escherichia coli, isolated, and functionally reconstituted in a liposomal system. The accessibility of each single Cys mutant to two methanethiosulfonate reagents was evaluated by determining the rate constants for inhibition of CTP function. These rate constants varied by over five orders of magnitude. With two independent data sets we observed peaks and troughs in the rate constant data at identical amino acid positions and a periodicity of 4 was observed from residues 123-137. Based on the pattern of accessibility we conclude that residues 123-137 exist as an alpha-helix. Although less certain, a combination of the rate constant data and the specific activity data with the single Cys mutants suggests that the alpha-helical secondary structure may extend to residue 113. Furthermore, the rate constant data define water-accessible and water-inaccessible faces of the helix. We infer that the water-accessible face comprises a portion of the substrate translocation pathway through the CTP, whereas the water-inaccessible surface faces the lipid bilayer. Finally, based on a combination of the CTP inhibition rate constant data and the existence of significant sequence identity with a transmembrane segment within glycophorin A that forms a portion of its dimer interface, a model for a putative CTP TMDIII-TMDIII' dimer interface has been developed.

Amino Acid Sequence↗
PubMed2001

Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate.

This study was designed to establish a simple and reliable assay method that could be routinely used in the clinical laboratory setting using liquid extraction and high-performance liquid chromatography (HPLC). In addition, a case of potential interaction of grapefruit juice with sildenafil citrate is presented. The peaks of sildenafil (measured as sildenafil salt) and internal standard were identified with an ultraviolet detector at 230 nm and detection limit at 10 ng/mL. In a single elderly male patient, grapefruit juice increased the Cmax of sildenafil by 42% (1067.7 ng/mL to 1517.0 ng/mL) although AUC was not significantly altered (4082.9 ng x h/mL to 4171.9 ng x h/mL) by grapefruit juice. Sildenafil could be determined in a simple and reliable method using HPLC with liquid extraction. This case indicated that grapefruit juice might increase the Cmax of sildenafil without significant change in AUC. A further study with an appropriate number of subjects is needed before determining the degree of interaction between grapefruit juice and sildenafil.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1981

Induction of ovulation by combined clomiphene citrate and dexamethasone treatment in clomiphene citrate nonresponders.

Fifteen anovulatory, oligomenorrheic, hyperandrogenic and normoprolactinemic women who failed to respond to prolonged clomiphene citrate (CC) treatment, were subsequently treated with CC and small doses of dexamethasone (Dex). Twelve (80%) of the patients ovulated according to BBT and progesterone values, and 7 (49%) conceived during 3--6 treatment cycles. Five of these pregnancies terminated in live, single, full term deliveries, one set of twins and one first trimester abortion. It is concluded that a regimen of combined CC and a small dose of Dex may be offered to CC nonresponders as an effective alternative to Menotropins--HCG treatment.

Adult↗
PubMed2005

N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of N-acetyl-cysteine (NAC), a mucolytic drug with insulin sensitizing properties, as an adjuvant therapy in subjects with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC). DESIGN: Placebo-controlled, double-blind randomized trial. SETTING: University-based hospital and private infertility practice. PATIENT(S): One hundred fifty women diagnosed with CC-resistant PCOS, aged 18-39 years undergoing therapy for infertility were included. INTERVENTION(S): The patients were assigned randomly to receive either NAC 1.2 g/d (group I) or placebo (group II) with CC 100 mg/d for 5 days starting at day 3 of the cycle. MAIN OUTCOME MEASURE(S): Ovulation rate and pregnancy rate (PR). RESULT(S): Combination of CC and NAC significantly increased both ovulation rate and PR in women with CC-resistant PCOS (49.3% vs. 1.3% and 21.3% vs. 0%, respectively). No cases of ovarian hyperstimulation syndrome (OHSS) were reported in the NAC group; two cases of miscarriage (12.5%) were reported. CONCLUSION(S): The NAC as an adjuvant to CC was more effective than placebo for CC-resistant patients with PCOS. It is safe and well tolerated.

Acetylcysteine↗
PubMed2001

Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone.

OBJECTIVE: To determine whether metformin treatment increases the ovulation and pregnancy rates in response to clomiphene citrate (CC) in women who are resistant to CC alone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Multicenter environment. PATIENT(S): Anovulatory women with the polycystic ovary syndrome (PCOS) who were resistant to CC. INTERVENTION(S): Participants received placebo or metformin, 500 mg three times daily, for 7 weeks. Information on reproductive steroids, gonadotropins, and oral glucose tolerance testing was obtained at baseline and after treatment. Metformin or placebo was continued and CC treatment was begun at 50 mg daily for 5 days. Serum P level > or =4 ng/mL was considered to indicate ovulation. With ovulation, the daily CC dose was not changed, but with anovulation it was increased by 50 mg for the next cycle. Patients completed the study when they had had six ovulatory cycles, became pregnant, or experienced anovulation while receiving 150 mg of CC. MAIN OUTCOME MEASURE(S): Ovulation and pregnancy rates. RESULT(S): In the metformin and placebo groups, 9 of 12 participants (75%) and 4 of 15 participants (27%) ovulated, and 6 of 11 participants (55%) and 1 of 14 participants (7%) conceived, respectively. Comparisons between the groups were significant. CONCLUSION(S): In anovulatory women with PCOS who are resistant to CC, metformin use significantly increased the ovulation rate and pregnancy rate from CC treatment.

Adolescent↗
PubMed2002

Use of dexamethasone and clomiphene citrate in the treatment of clomiphene citrate-resistant patients with polycystic ovary syndrome and normal dehydroepiandrosterone sulfate levels: a prospective, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effects of short-course administration of dexamethasone (DEX) combined with clomiphene citrate (CC) in CC-resistant patients with polycystic ovary syndrome (PCOS) and normal DHEAS levels. DESIGN: Prospective, double-blind, placebo-controlled, randomized study. SETTING: Referral university hospitals. PATIENT(S): Two hundred thirty women with PCOS and normal DHEAS who failed to ovulate after a routine protocol of CC. INTERVENTION(S): The treatment group received 200 mg of CC from day 5 to day 9 and 2 mg of DEX from day 5 to day 14 of the menstrual cycle. The control group received the same protocol of CC combined with placebo. MAIN OUTCOME MEASURE(S): Follicular development, hormonal status, ovulation rate, pregnancy rate. RESULT(S): Mean follicular diameters were 18.4124 +/- 2.4314 mm and 13.8585 +/- 2.0722 mm for the treatment and control groups, respectively. Eighty-eight percent of the treatment group and 20% of the control group had evidence of ovulation. The difference in the cumulative pregnancy rate in the treatment and control groups was statistically significant. CONCLUSION(S): Hormonal levels, follicular development, and cumulative pregnancy rates improved with the addition of DEX to CC in CC-resistant patients with PCOS and normal DHEAS. This regimen is recommended before any gonadotropin therapy or surgical intervention.

Adult↗
PubMed1986

Comparison of human menopausal gonadotropin, clomiphene citrate, and combined human menopausal gonadotropin-clomiphene citrate stimulation protocols for in vitro fertilization.

Human menopausal gonadotropins (hMG) and clomiphene citrate (CC), either alone or in combination, are frequently used for in vitro fertilization (IVF) in an attempt to maximize the number of oocytes recovered and the number of embryos transferred. However, direct comparison of the relative efficacy of these protocols in the same institution has been limited. To evaluate this question, the authors examined the outcome of 304 consecutive women attempting IVF. One hundred eighty-one women received hMG, 42 received CC, and 81 received combination hMG/CC. The percentages of women undergoing laparoscopy were not different among the groups (69%, 71%, and 74%, respectively), nor were the rates of oocyte recovery (94%, 100%, and 100%). However, the percentage of women achieving oocyte fertilization (77%, 83%, and 93%) and embryo transfer (73%, 83%, and 90%) were significantly greater among those who had received hMG/CC stimulation. A comparison of hMG/CC with hMG and CC cycles revealed a statistically significant increase in the total number of developing follicles (4.5 +/- 0.3, 3.3 +/- 0.2, and 3.1 +/- 0.3, respectively; P = 0.0137), total oocytes recovered (4.1 +/- 0.3, 3.2 +/- 0.2, and 2.5 +/- 0.2; P = 0.0011), and embryos transferred (2.2 +/- 0.2, 1.4 +/- 0.2, and 1.4 +/- 0.2; P = 0.0013). However, there was no significant difference in the occurrence of ongoing pregnancies. Thus, in terms of the per-patient number of follicles, oocytes, and embryo transfers, combined hMG/CC stimulation appears to be superior to either hMG or CC alone. However, to date the combined regimen has not improved pregnancy rates.

Clomiphene↗