Biomedical subjects

K Erb

Publications and source records attributed to K Erb.

At least 19 recordsLinked to original sources

PubMed2001

Pharmacodynamic effects and plasma pharmacokinetics of single doses of cetrorelix acetate in healthy premenopausal women.

OBJECTIVE: To investigate the pharmacodynamic effects and plasma pharmacokinetics of single subcutaneous doses of cetrorelix acetate in healthy premenopausal women. SETTING: Phase I clinical research unit. PATIENT(S): Healthy, premenopausal women aged 19 to 35 years. INTERVENTION(S): Single subcutaneous morning doses of cetrorelix acetate (1, 3, or 5 mg peptide base) were investigated in a randomized, single-blind, placebo-controlled, parallel-group design. After a control cycle, 36 women received cetrorelix acetate (12 per dose) and 12 received placebo on the eighth individual cycle day. Transvaginal ultrasound was performed, and blood samples for LH, FSH, E2 were collected during both cycles and for pharmacokinetics up to 168 hours after dosing. The serum hormone levels were determined by electrochemicoluminescence immunoassay and plasma cetrorelix concentrations by radioimmuno assay. RESULTS: Cetrorelix acetate administration led to a rapid, marked, and reversible suppression of serum LH, E2, and to a lesser extent FSH concentrations. The median intra-individual shifts between treatment and control cycle were -1.0, 4.0, 8.0, and 9.5 days for serum LH maximum and -1.0, 4.5, 7.0, and 10.0 days for ovulation following placebo or 1, 3, and 5 mg cetrorelix acetate, peptide base, respectively. The area under the concentration-time curve (AUC) and peak cetrorelix concentrations in plasma (Cmax) increased proportionally with dose. CONCLUSIONS: Cetrorelix acetate showed pronounced and reversible LH and E2 suppression and a dose-dependent postponement of LH surge and ovulation after single subcutaneous administrations to healthy premenopausal women. Dose proportionality over the range of 1 mg to 5 mg cetrorelix acetate, peptide base was demonstrated.

Adult↗

PubMed2001

Human menopausal gonadotropin versus recombinant follicle-stimulating hormone in normogonadotropic women down-regulated with a gonadotropin-releasing hormone agonist who were undergoing in vitro fertilization and intracytoplasmic sperm injection: a prospective randomized study.

OBJECTIVE: To evaluate clinical and endocrinological effects of intranasal (IN) vs. subcutaneous (SC) GnRH-a for pituitary down-regulation combined with hMG vs. rFSH. DESIGN: Prospective, randomized study. SETTING: University hospital, IVF unit. PATIENT(S): Three hundred seventy-nine normogonadotropic women eligible for IVF or ICSI. INTERVENTION(S): Randomization to intranasal (IN) or SC GnRH-a and to hMG or rFSH. MAIN OUTCOME MEASURE(S): Oocytes retrieved, embryos developed, clinical pregnancy, and delivery rates. Serum hormone concentrations on stimulation days 1 (S1) and 8 (S8), and oocyte pick-up (OPU) day. RESULT(S): After randomization, four groups were formed: IN/hMG (n = 100), IN/FSH (n = 98), SC/hMG (n = 89), and SC/FSH (n = 92). Mean number of oocytes retrieved and of transferable and transferred embryos were similar in the four groups. Clinical pregnancy rate per started cycle was significantly higher in the IN/HMG group than in the SC/FSH group (P<.05) and was intermediate in the two remaining groups. Se-LH on S8 in the two SC groups was significantly lower than in the two IN groups. Se-E2 on S8 in the SC/FSH group was significantly lower than in the other three groups. CONCLUSION(S): The clinical and endocrinological outcome in IVF and ICSI-treated normogonadotropic women is significantly influenced by mode of down-regulation as well as gonadotropin formulation.

Administration, Intranasal↗

PubMed2001

Intrauterine insemination with donor semen. An evaluation of prognostic factors based on a review of 1131 cycles.

OBJECTIVE: To identify prognostic factors influencing the outcome of infertility treatment using intrauterine insemination with donor semen (IUI-D). DESIGN: Retrospective study of all patients undergoing IUI-D between August 1st, 1990 and July 31st, 1998. SETTING: University-affiliated infertility clinic. PATIENTS: Three hundred and five couples undergoing 1131 IUI-D treatment cycles. MAIN OUTCOME MEASURES: Type of hormonal treatment, number of follicles, length of follicular phase, endometrial pattern, female age, infertility diagnosis and semen quality related to clinical pregnancy rate, cumulative birth rate and multiple gestations. RESULTS: Throughout the nine year period the overall clinical pregnancy rate per cycle was 22.3%, with an increase from 12.9% in 1990 to 34.6% in 1998. The multiple birth rate was 20.6%. The birth rate per couple was 61.1% after a mean of 3.2 treatment cycles. The pregnancy rate was highest in the first treatment cycle and the cumulative birth rate rose only slightly after the sixth treatment cycle. The following parameters were positively and significantly correlated to a successful outcome of IUI-D: i) the first treatment cycle - compared to the following up to six treatment cycles; ii) number of mature follicles - more than one - at the time of insemination, however, with an unacceptable high rate of multiple pregnancies when more than 3 mature follicles were present; iii) time of insemination after the 12th day in the cycle; iv) insemination after ovulation has occurred and; v) female age under 30 years. CONCLUSIONS: IUI-D is a simple and inexpensive treatment giving acceptable pregnancy rates for up to six treatment cycles if at least 2 mature follicles have developed at the time of insemination, which implies that hormonal ovarian stimulation and induction of ovulation is used, and ovulation has occurred at the time of insemination, which ought to take place after cycle day (cd) 12 with at least two million motile spermatozoa.

Adult↗

PubMed2001

Homologous intrauterine insemination. An evaluation of prognostic factors based on a review of 2473 cycles.

OBJECTIVE: To identify prognostic factors influencing the outcome of infertility treatment using homologous intrauterine inseminations (IUI-H). DESIGN: Retrospective study of all patients undergoing IUI-H at the Fertility Clinic, Odense University Hospital from August 1st, 1990 to July 31st, 1998. SETTING: University-affiliated infertility clinic. PATIENTS: Eight hundred and ninety-three couples undergoing 2473 IUI-H treatment cycles. MAIN OUTCOME MEASURES: Infertility diagnosis, female age, number of follicles, type of hormonal treatment, length of follicular phase, endometrial pattern, and semen quality related to clinical pregnancy rate, cumulative birth rate and multiple gestations. RESULTS: Throughout the nine year period the overall clinical pregnancy rate per IUI-H cycle was 11.9% with a significant increase from 8.7% in 1990 to 14.8% in 1998. The multiple birth rate was 18.1%. The birth rate per couple was 27.2% after a mean of 2.8 treatment cycles. The pregnancy rate was highest in the first treatment cycle and the cumulative birth rate rose only slightly after the fourth treatment cycle. Of the main outcome measures the following were positively and significantly related to a successful outcome of IUI: i) The first treatment cycle - compared to the following up to six treatment cycles; ii) number of mature follicles up to five - at the time of insemination, however, with an unacceptable high rate of multiple pregnancies with more than 4 mature follicles; iii) use of CC/hMG-FSH as compared to CC only for ovarian stimulation; iv) number of motile sperms inseminated exceeding 5 million; v) time of insemination between the 13th and the 16th day in the cycle and vi) anovulatory or idiopathic infertility. CONCLUSIONS: IUI-H is a simple and inexpensive treatment giving acceptable pregnancy rates for up to four treatment cycles providing that at least 3 to 4 mature follicles have developed at the time of insemination, which implies that hormonal ovarian stimulation and induction of ovulation is used, that insemination occurs between cycle day 13 and 16 and that at least 5 million motile sperms are available for insemination. Our results indicate that in the presence of tubal pathology or less than 5 million motile sperms, the couples should be referred directly to IVF-treatment.

Adult↗

PubMed2001

Upon prolonged allergen exposure IL-4 and IL-4Ralpha knockout mice produce specific IgE leading to anaphylaxis.

BACKGROUND: IL-4 and IL-13 are key regulators in atopic disorders and both signal through the receptor chain IL-4Ralpha. IL-4 and IL-13 are also the only cytokines known to induce class switching to IgE. We sought to compare allergen-specific IgE responses and allergic reactivity of wild-type (wt) mice with IL-4-/- and IL-4Ralpha-/- mice, which lack both IL-4 and IL-13 functions. METHODS: BALB/c wt, IL-4-/- and IL-4Ralpha-/- mice were immunized with ovalbumin intranasally or intraperitoneally and specific antibody titers were measured by ELISA. Bronchoalveolar lavage fluids and lung tissue were analyzed cytologically and histologically. Allergic reactivity was determined by active cutaneous anaphylaxis and anaphylactic shock. RESULTS: wt mice immunized intranasally or intraperitoneally showed high titers of specific IgE 3 and 6 weeks after primary sensitization, resulting in cutaneous anaphylaxis and anaphylactic shock upon challenge. Intranasal sensitization resulted in airway eosinophilia and goblet cell metaplasia. In contrast, IL-4-/- and IL-4Ralpha-/- mice showed no specific IgE after 3 weeks, but produced high titers after 6 weeks. At this time cutaneous anaphylaxis and anaphylactic shock could be induced as in wt mice, but lung pathology was absent. CONCLUSIONS: We conclude that upon long-term allergen exposure, alternative switch mechanisms independent of IL-4 and IL-4Ralpha may induce IgE but not asthma-like lung pathology. This may be relevant for the development of allergic disease, since long-term allergen exposure is a frequent condition during allergic sensitization.

Allergens↗

PubMed2000

Selective suppression of inhibitory synaptic transmission by nocistatin in the rat spinal cord dorsal horn.

Nociceptin/orphanin FQ (N/OFQ) and nocistatin (NST) are two recently identified neuropeptides with opposing effects on several CNS functions, including spinal nociception. The cellular mechanisms that underlie this antagonism are not known. Here, we have investigated the effects of both peptides on synaptic transmission mediated by the three fast neurotransmitters l-glutamate, glycine, and GABA in the superficial layers of the rat spinal cord horn, which constitute the first important site of integration of nociceptive information in the pain pathway. NST selectively reduced transmitter release from inhibitory interneurons via a presynaptic Bordetella pertussis toxin-sensitive mechanism but left excitatory glutamatergic transmission unaffected. In contrast, N/OFQ only inhibited excitatory transmission. In the rat formalin test, an animal model of tonic pain in which N/OFQ exerts antinociceptive activity, NST induced profound hyperalgesia after intrathecal application. Similar to glycine and GABA(A) receptor antagonists, NST had no significant effects in the rat tail-flick test, a model of acute thermal pain. Our results provide a cellular basis for the antagonism of N/OFQ and NST and suggest the existence of a so far unidentified membrane receptor for NST. In addition, they support a role of NST as an endogenous inhibitor of glycinergic and GABAergic neurotransmission in the sensory part of the spinal cord and as a mediator of spinal hyperalgesia.

Analgesics, Opioid↗

PubMed2000

The influence of infections on the development and severity of allergic disorders.

The frequency and severity of atopic disorders are steadily increasing, particularly in developing countries. The reason for this observation is not clear. Recent studies indicate that infections with viruses and especially with bacteria early in life may help to inhibit allergic Th2 responses by skewing the immune system towards Th1 responses. However, infections can also lead to the exacerbation of atopic disorders.

Animals↗

PubMed2000

Molecular diagnosis of a familial nonhemolytic hyperbilirubinemia (Gilbert's syndrome) in healthy subjects.

Recent research has shown that congenital nonhemolytic low grade hyperbilirubinemias in patients with Gilbert's syndrome (GS) are linked to mutations in the TATA box upstream of the uridine 5'-diphosphoglucose glucuronosyltransferase (UGT1A1) gene leading to an impaired bilirubin glucuronidation. In routine clinical practice GS patients can, however, only be suspected by exclusion of other causes of hyperbilirubinemia or substantial liver diseases. We developed a new, sensitive, convenient, and economic polymerase chain reaction (PCR) method for the rapid and reliable identification of gene polymorphisms in the TATA box of the UGT1A1 gene using fluorescence resonance energy transfer (FRET). With this procedure the genotype frequency in a cohort of 266 unrelated individuals from Southern Germany was investigated and the allelic distribution for individual genotypes was 43:45:12 for the (TA)(6)TAA:(TA)(6)TAA/(TA)(7)TAA:(TA)(7)TAA alleles, respectively. The homozygous (TA)(7)TAA genotype was strongly associated with suspected Gilbert's patients and its prevalence in our cohort of 266 Southern German individuals was 12.4%. In this cohort total mean serum bilirubin levels ranged from 5 micromol/L (wild-type 6/6 allele) to 57 micromol/L serum total bilirubin (mutant 7/7 homozygous allele). Median (interquartile range) serum total bilirubin levels were 12 (6) and 21 (13) for the homozygous wild-type and mutant allele, respectively. Our assay enables individual guidance for dose adjustment in suspected GS patients undergoing long-term drug therapies, especially if glucuronidation via UGT1A1 is a major metabolic pathway.

Adult↗

PubMed2000

Pituitary and gonadal endocrine effects and pharmacokinetics of the novel luteinizing hormone-releasing hormone antagonist teverelix in healthy men--a first-dose-in-humans study.

UNLABELLED: BACKGROUND. Teverelix is a novel synthetic peptidic luteinizing hormone-releasing hormone (LHRH) antagonist. METHODS: Single subcutaneous morning doses of teverelix acetate (either 0.5, 1, 2, 3, or 5 mg base) were investigated in a randomized, single-blind, placebo-controlled, dose-escalating parallel-group design in healthy men. Six subjects received teverelix, and two subjects received placebo per dose level. Blood samples for lutropin, luteinizing hormone (LH), and follitropin, follicle-stimulating hormone (FSH), and testosterone, as well as for pharmacokinetics, were withdrawn up to 120 hours after dosing. Serum hormone levels were determined by electrochemicoluminescence immunoassays, and plasma teverelix concentrations were determined by radioimmunoassay. RESULTS: Teverelix led to a rapid, marked suppression of LH, testosterone and, to a lesser extent, FSH. Median maximum suppressions compared with predose levels were -93% for LH and -54% for FSH after teverelix 5 mg, and -93% for testosterone after teverelix 3 mg, respectively. After 5 mg teverelix, testosterone suppression <1 ng/mL started a median of 12 hours after dosing and lasted for a median of 33 hours. The duration of testosterone suppression increased with dose. Geometric means of peak teverilix plasma concentrations were 4.5 ng/mL (0.5 mg teverelix) to 49.0 ng/mL (5 mg teverelix) and tmax occurred between 1 and 4 hours after dosing. Geometric means of the area under the teverelix plasma concentration-time course from zero to time of the last quantifiable plasma concentration [AUC(O-tlast)] were 54.9 ng x h/mL (0.5 mg teverelix) to 881.8 ng x h/mL (5 mg teverelix). Median values for apparent terminal half-lives ranged from 24 to 75 hours. The most frequently reported adverse events were short-lasting mild injection-site reactions. CONCLUSIONS: Teverelix showed pronounced LH and testosterone suppressive effects after single subcutaneous doses in healthy men. Duration of hormone suppression increased with dose. Teverelix was well tolerated. This profile indicates potential for further clinical use.

Adult↗

PubMed2000

Pharmacokinetic and pharmacodynamic modeling of cetrorelix, an LH-RH antagonist, after subcutaneous administration in healthy premenopausal women.

PURPOSE: The purpose of this study was the development of pharmacokinetic and pharmacodynamic models for the luteinizing hormone (LH) suppression and subsequent shift in LH surge and follicle-stimulating hormone by cetrorelix in women. BACKGROUND: Cetrorelix is a potent luteinizing hormone-releasing hormone (LH-RH) antagonist and is used for the prevention of the premature ovulation indicated by an LH surge in in vitro fertilization. The pharmacokinetic and pharmacodynamic relationship for the suppression and the shift in the LH surge has not yet been established. METHODS: In a placebo-controlled study, single subcutaneous doses of 1, 3, and 5 mg of cetrorelix were given to 36 subjects on day 8 of the natural menstrual cycle. Cetrorelix, LH, follicle-stimulating hormone, estradiol, and progesterone were determined. RESULTS: Cetrorelix pharmacokinetics were described by a 2-compartment model with a terminal half-life of 56.9 +/- 27.1 hours. Mean shift in LH surge was by 4.1, 7.5, and 9.3 days with the 1-, 3-, and 5-mg doses, respectively. An indirect response sigmoid Emax model was developed for the suppression of LH and the shift in the LH surge. The inhibitory concentration of 50% (for LH suppression) and median effective concentration (for surge shift) estimates were 3.6 ng/mL and 1.6 ng/mL, respectively. The suppression of follicle-stimulating hormone was described by a similar Emax model, with an inhibitory concentration of 50% of 7.25 ng/mL. CONCLUSIONS: A pharmacokinetic and pharmacodynamic model was developed for the transient initial suppression of LH and the subsequent shift in the LH surge after 3 single subcutaneous doses of cetrorelix without ovarian stimulation. A separate model was developed for the suppression of follicle-stimulating hormone by cetrorelix. The shift in the LH surge could be adequately described by the model.

Adult↗

PubMed2000

Danish National IVF Registry 1994 and 1995. Treatment, pregnancy outcome and complications during pregnancy.

SUBJECT: Data from the compulsory Danish National IVF Registry from 1994 and 1995 regarding treatments, abortions and complications following assisted reproductive technologies. METHODS: Data were generated through registries and compared to pregnancies in Denmark in 1995. Those pregnancies that resulted in a delivery were compared to a matched control group. RESULTS: In 1994 and 1995 5219 women were treated in 9471 initiated cycles. The numbers increased over the period. The overall delivery rate per initiated cycle was 19%, egg donation 24%, IVF 20%, ICSI 16% and frozen egg replacement 10%. The rates increased over the period. The rate of spontaneous abortions was highest for ICSI (25%) and egg donation (27%). For IVF and ICSI the birth rates per transfer of 1 embryo was 13, 1%, 2 embryos 25, 4%, 3 embryos 25, 8% and 4 or more 3, 8%. Transfer of 2 embryos resulted in 75% singleton, 25% twin and 0.2% triplet deliveries. After transfer of 3 embryos the corresponding rates were 68%, 29% and 4%. No quadruplet deliveries occurred. Totally, 1.4% reported complications to the treatment, the most frequent being ovarian hyperstimulation syndrome. In the study group 5.8% of the women who gave birth were diagnosed with imminent abortion vs. 3.0% in the control group (OR 1.98, CI 1.41-2.78). CONCLUSIONS: Transfer of three embryos did not result in higher pregnancy rates as compared to transfer of two embryos. The first data from the Danish IVF Registry support data from other registries regarding treatment, pregnancy outcome and complications during pregnancy.

Abortion, Spontaneous↗

PubMed1999

Stereoselective disposition of tiaprofenic acid enantiomers in rats.

The pharmacokinetics and metabolic chiral inversion of the S(+)- and R(-)-enantiomers of tiaprofenic acid (S-TIA, R-TIA) were assessed in vivo in rats, and in addition the biochemistry of inversion was investigated in vitro in rat liver homogenates. Drug enantiomer concentrations in plasma were investigated following administration of S-TIA and R-TIA (i.p. 3 and 9 mg/kg) over 24 hr. Plasma concentrations of TIA enantiomers were determined by stereospecific HPLC analysis. After administration of R-TIA it was found that 1) there was a time delay of peak S-TIA plasma concentrations, 2) S-TIA concentrations exceeded R-TIA concentrations from approximately 2 hr after dosing, 3) Cmax and AUC(0-infinity) for S-TIA were greater than for R-TIA following administration of S-TIA, and 4) inversion was bidirectional but favored inversion of R-TIA to S-TIA. Bidirectional inversion was also observed when TIA enantiomers were incubated with liver homogenates up to 24 hr. However, the rate of inversion favored transformation of the R-enantiomer to the S-enantiomer. In conclusion, stereoselective pharmacokinetics of R- and S-TIA were observed in rats and bidirectional inversion in rat liver homogenates has been demonstrated for the first time. Chiral inversion of TIA may involve metabolic routes different from those associated with inversion of other 2-arylpropionic acids such as ibuprofen.

Animals↗

PubMed1999

Dose-proportionality of oral thioctic acid--coincidence of assessments via pooled plasma and individual data.

Thioctic acid (TA), a racemate of R-(+)- and S-(-)-enantiomers of alpha-lipoic acid, acts as a powerful lipophilic, free-radical scavenger and is used in the treatment of diabetic neuropathy. This trial investigated the dose-linearity of enantiomer pharmacokinetics following the oral administration of single doses of 50 to 600 mg TA (formulation provided by ASTA (Medica)) in healthy volunteers. TA enantiomer concentrations in individual and pooled plasma samples were determined using enantioselective, high-performance liquid chromatography. TA was rapidly absorbed (tmax, 0.5 to 1 h). Maximum plasma concentrations (Cmax) of the R-(+)-enantiomer were about 40-50% higher than those of the S-(-)-enantiomer (50 mg: 135.45 ng/ml R-(+)-TA, 67.83 ng/ml S-(-)-TA; 600 mg: 1812.32 ng/ml R-(+)-TA, 978.20 ng/ml S-(-)-TA; geometric means). The decline observed in the plasma concentration was steep (t1/2, 0.5 h). The dose-linearity and proportionality of pharmacokinetic parameters could be demonstrated on an intra-individual basis and for the group geometric means. An analysis of pooled plasma samples proved to be a suitable means for deriving reliable first-sight results prior to individual assessments.

Adult↗

PubMed1999

Danish National In-Vitro Fertilization Registry 1994 and 1995: a controlled study of births, malformations and cytogenetic findings.

This paper reports data from the Danish in-vitro fertilization (IVF) registry from 1994 to 1995 including data on treatments and the results of these (perinatal outcome, cytogenetic findings and fetal malformations) in comparison with a control group matched for maternal age, parity, multiplicity and year of birth. There were 1756 deliveries of 2245 children (24.3% twins, 1.8% triplets). The rate of prematurity among IVF children was 23.8% (NS) [singletons 7. 3% (P < 0.05), twins 41.2% and triplets 93.5%], 23.6% weighed <2500 g [singletons 7% (P < 0.05), twins 42.2% and triplets 87.1%]. The perinatal mortality rate was 21.8 in the study group compared to 17. 4 in the control group (NS). In total, 13.2% of all clinical pregnancies and 15.4% of the pregnancies that resulted in a delivery had a prenatal genetic examination. Of all examined, 3.5% had an abnormal karyotype. In total, 107 (4.8%) children in the study group and 103 (4.6%) in the control group were born with malformations (NS), compared to 2.8% in the background population. Our results indicate that it is the characteristics of the patients and multiplicity of pregnancy, rather than the assisted reproductive technology that determines the fetal risks of IVF pregnancies compared to the background population.

Adult↗

PubMed1999

A Danish national cohort of 730 infants born after intracytoplasmic sperm injection (ICSI) 1994-1997.

This national cohort study included all clinical pregnancies obtained after intracytoplasmic sperm injection (ICSI) registered in Denmark between January 1994 and July 1997 at five public and eight private fertility clinics. Laboratory and clinical data were obtained from the fertility clinics. The couples answered a questionnaire regarding the pregnancy and the health of the child (response rate 94%). Data validation was carried out through discharge charts. The mean age of the women was 32.1 years. In 84.2% of couples, male factor was the main reason for performing ICSI, and in 4.8% epididymal spermatozoa were used. The mean number of embryos replaced was 2.3 (range 1-3) and in 95% of cases fresh embryos were transferred. Only 183 women (28.5%) underwent prenatal diagnosis, resulting in 209 karyotypes with seven (3.3%) chromosome aberrations. Six major chromosomal abnormalities (2.9%) and one inherited structural chromosome aberration (0.5%) were found, but no sex chromosome aberrations. The frequency of multiple birth, Caesarean section rate, gestational age, preterm birth, and birth weight were comparable with previous studies. The perinatal mortality rate was 13.7 per 1000 children born with a gestational age of 24 weeks or more. In 2.2% (n = 16) of the liveborn infants, and in 2.7% (n = 20) of all infants, major birth defects were reported by the parents. Minor birth defects were found in nine liveborn infants (1.2%). In conclusion, the results of this study on outcome of ICSI pregnancies are in line with earlier reports, except that no sex chromosome abnormalities were found.

Adult↗

PubMed1999

Fetal antigen 1, an EGF multidomain protein in the sex hormone-producing cells of the gonads and the microenvironment of germ cells.

Fetal antigen 1 (FA1), an epidermal growth factor (EGF) multidomain glycoprotein, was investigated in the human reproductive system. Immunohistochemical analysis of the male reproductive system revealed staining for FA1 in the Leydig cells only. Concentrations of FA1 in seminal plasma and serum were similar and significantly correlated in weekly samples from three men (P < 0.0065). The concentrations in seminal plasma from vasectomized men (n = 4) were not significantly different from those of normal men (n = 187). The concentration of FA1 in seminal plasma was significantly correlated with the sperm counts of normozoospermic men (P < 0.0001), and significantly higher in seminal plasma from men with sperm counts > 20 x 10(6)/ml, compared with those with counts </= 20 x 10(6)/ml (P < 0. 0001). Immunohistochemical analysis of the ovary showed the presence of FA1 in the theca interna and the hilus cells but not in the granulosa cells or the oocyte. In follicular fluid the concentration of FA1 (median; 73.3 ng/ml, n = 28) was three times higher than that of serum (median; 23.8 ng/ml). These data suggest a role for this novel member of the EGF superfamily in relation to human reproduction, but further experiments are needed to define the biological function and to elucidate its clinical potential.

Adult↗

PubMed1998

[The effectiveness of in vitro fertilization. A cohort study of 300 couples].

A cohort of 300 couples, starting their first in-vitro fertilization (IVF) attempt between 1990 and 1992, were followed until completion of their treatment. A total of 897 treatment cycles were initiated. Of these 213 (23.7%) were cancelled, giving a total of 684 embryo replacements. One hundred and forty-one (47%) couples completed their treatment with delivery of at least one healthy baby. Ninety-eight (31.3%) couples completed their treatment without achieving delivery of a living baby, and 40 (13.7%) couples cancelled their treatment due to varying reasons. The treatment in seven couples was cancelled before completion due to medical reasons. In 12 women no transfer took place. IVF treatment is an effective procedure giving a "baby take home rate" of 47% within one to three cycles. A cohort study gives a realistic view of the probability of childbirth.

Adult↗

PubMed1998

Immunoregulatory networks in asthma.

It is now well established that a subset of T-cell-derived cytokines (termed Th2 cytokines) programme the timing and characteristics of atopic airway disease including mast-cell sensitization, eosinophil and lymphocyte infiltration and recently mucus secretion. To date, attempts to devise ways to selectively limit the activities of Th2 cytokine-producing cells have been frustrated. However, the recent identification of the molecules which direct the activation and maturation of T cells has led to some successful attempts to block the activities of Th2 cells in models of atopic airway inflammation. Some of the agents with the most potential include antagonists of the T-cell costimulatory molecule CD28, local stimulators of the Thl subset of cytokines such as the BCG vaccine and potentially, antagonists of the eotaxin chemokine receptor and agonists of the T-cell costimulatory molecule CTLA-4. Not only do such agonists and antagonists represent potential new therapies, they could represent a rich hunting ground for those who aim to determine the ways in which atopic airway disease can be diagnosed and understood.

Abatacept↗