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Biomedical subjects

B Hinney

Publications and source records attributed to B Hinney.

At least 19 recordsLinked to original sources
PubMed2002

[Hormonal therapy and chemotherapy of endometrial cancer].

Endometrial cancer is usually diagnosed at an early stage where surgery alone is the adequate therapy. Chemotherapy and hormonal treatment are therefore almost exclusively performed in palliative situations. Hormonal treatment with progestogens (medroxyprogesterone acetate and megestrol acetate) should be the therapy of choice primarily as these drugs are very well tolerated. Tamoxifen and GnRH analogs are further options but are seldom used. The response rates to hormonal treatment are relatively low (max. 25 %) with short remissions in most cases. - So far neither hormonal treatment nor cytotoxic chemotherapy has been shown to have substantial benefits in the adjuvant setting. In some selected high risk cases (serous papillary carcinomas, extra uterine manifestation) adjuvant chemotherapy may be an option following surgery, before or after radiotherapy. Age, general condition and morbidity of the patients need to be considered as limiting factors for chemotherapy. Crucial for the prognosis of all endometrial cancer patients however, is the stage adapted surgery. - Cytotoxic chemotherapy has failed to bring a break through in the therapy of advanced endometrial cancer. Cisplatin plus doxorubicin is the standard combination to date, with anthracyclines being the more important component. In a mono-therapy setting, doxorubicin and epirubicin are well tolerated and convenient in their efficacy. For recurrent and metastatic disease, docetaxel is being evaluated for efficacy and side effects in a multicenter phase II trial.

Antineoplastic Agents, Hormonal↗
PubMed2001

LH pulses and the corpus luteum: the luteal phase deficiency LPD).

The proper function of the GnRH pulse generator in the hypothalamus is essential for normal ovarian function, hence also for proper function of the corpus luteum. During the luteal phase LH pulses stimulate progesterone release, which is essential for normal endometrial transformation. Approximately one-half of all luteal phase deficiencies (LPD) are due to improper function of the GnRH pulse generator. Obviously, following ovulation the increased serum progesterone levels oversuppress the GnRH pulse generator, resulting in too few LH pulses and therefore improper luteal function. Also, latent hyperprolactinemia may lead to an LPD which can be effectively treated with plant extracts containing dopaminergic (prolactin-suppressing) compounds. Our increasing knowledge of auto- and paracrine mechanisms between nonsteroidogenic and steroidogenic cells now allow subclassification of LPDs of ovarian origin. The so-called small luteal cells are LH-responsive. If they develop improperly the regularly occurring LH pulses are unable to stimulate progesterone secretion from the small luteal cells, which results in what we call the small luteal cell defect. In addition, there is also evidence that the large luteal cells may function improperly. Hence, basal progesterone release is too low while LH-stimulated progesterone release from the small luteal cells appears to be intact. This subclassification of luteal phase deficiency results in the suggestion of different treatments. In cases where the corpus luteum is LH-responsive, such as the hypothalamic corpus luteum insufficiency and the large luteal cell defect, HCG treatment or pulsatile treatment with GnRH is advisable. In the case of LH/hCG-unresponsive small luteal cell defect a progesterone substitution is suggested.

Animals↗
PubMed2001

Pseudo dicentric chromosome (5;21): a rare example of maternal germline mosaicism.

Karyotyping of a malformed male newborn revealed the unbalanced karyotype of 46,XY, psudic(5;21)(q12;p13), +5 resulting in trisomy for the short arm of chromosome 5 and partial trisomy for 5q. Both parents had normal karyotypes in their peripheral blood lymphocytes. A second pregnancy ended in a miscarriage at 16 weeks gestation, sonographically 12 weeks. Karyotyping of chorionic villi from the abortus revealed the same unbalanced karyotype that had been identified in the first child. Fluorescence in-situ hybridization analysis confirmed a trisomy 5p. Microsatellite marker analysis ruled out illegitimacy and proved the maternal origin of the trisomic section of chromosome 5. Extended chromosome analysis of 60 metaphase cells from maternal skin fibroblasts and 40 metaphase cells from lymphocytes did not reveal mosaicism for psudic(5;21). These findings suggest the presence of a maternal germline mosaicism.

Abnormalities, Multiple↗
PubMed2001

Androblastoma of the ovary: clinical, diagnostic and histopathologic features.

Androblastomas of Sertoli-Leydig cell tumors of the ovaries are classified into the group of sex cord stromal tumors and represent an extremely rare form of tumor (0.2% of all ovarian tumors) in women. Their malignant potential is lower than that of epithelial ovarian cancer. They cause signs of virilization, although these are not obligatory. In many cases secondary amenorrhea is the only symptom of the disease. This leads to an intensive search for the source of the disorder. Frequently only the elevated production of androgens gives a preoperative clue to the tumor type. The recommendation to include the measurement of androgen levels in the routine diagnosis of secondary amenorrhea must therefore be endorsed. The tumors are usually sonographically identifiable; in differential diagnosis, hyperandrogenemia of other origins (e.g., Cushing's disease, adrenal hyperplasia, pituitary adenoma, other causes of ovarian and adrenal androgen hypersecretion, intersexuality, medically induced androgenization) have to be ruled out. In view of the good prognosis, the therapy of choice consists simply in adnexectomy of the affected side. With regular measurement of serum androgen levels an effective control of the course of the disorder is possible. A conclusive pathological diagnosis is difficult as heterologous tumors and mixed tumors exist and, furthermore, other tumor types are capable of imitating Sertoli-Leydig cell tumors.

Androgens↗
PubMed2000

Homozygous factor V Leiden mutation in a woman with multiple adverse pregnancy outcomes.

We report a case with one intrauterine fetal death (IUFD) at 32 weeks of gestation, one premature delivery at the same week, and one abortion of unknown etiology at 12 weeks of gestation. We discuss that the presence of homozygosity for Factor V Leiden may be associated with placental insufficiency in this woman. Application of anticoagulant therapy may have been beneficial in her current pregnancy.

Abortion, Habitual↗
PubMed2000

Features of Antley-Bixler syndrome in an infant born to a mother with pregnancy luteoma.

UNLABELLED: We report a female newborn with characteristic signs of Antley-Bixler syndrome (ABS) such as midface hypoplasia, radiohumeral synostosis and multiple joint contractures. The newborn also presented ambiguous genitalia, stage Prader V, and congenital adrenal hyperplasia. The mother experienced midterm virilization due to a pregnancy luteoma. Her elevated androgen levels and virilization symptoms normalized post partum without treatment. The newborn had elevated serum testosterone and 17-OH-progesterone levels which remained elevated because of a 21-hydroxylase deficiency. The child's treatment in order of priority was: hydrocortisone substitution, craniofacial/skeletal anomaly management and surgical correction of the external genitalia. Mutations in the genes for fibroblast growth factor (FGF) 8 and receptors FGFR1, FGFR2, and FGFR3 were not detected. CONCLUSION: A newborn girl with manifestations of the Antley-Bixler syndrome showed severe virilization probably caused by the association of a mild 21-hydroxylase deficiency and maternal hyperandrogenism due to a pregnancy luteoma. Abnormalities of androgen metabolism may be responsible for virilization reported in other cases of the Antley-Bixler syndrome.

Adrenal Hyperplasia, Congenital↗
PubMed2000

X-Y sperm selection: fact or fiction?

Selecting the gender of offspring has given rise to various and sometimes amusing stories. But regardless of which prefertilisation technique is used to influence the sex ratio of offspring it must fulfill certain criteria. First of all it must achieve a complete separation of the X and Y bearing sperm in sufficient quantities. Secondly sperm must be viable after separation and capable of fertilising. Sex preselection methods can be divided into two general groups which either separate spermatozoa on the basis of subtle physical or kinetic features or those which rely on distinctive nuclear characteristics unique either to X or Y chromosome bearing sperm. These, in turn, can be divided into in vivo methods designed to produce optimal conditions for fertilisation by either the X or Y bearing sperm, or in vitro sperm separation methods designed to separate X or Y bearing sperm. According to all published data, the different separation techniques have been shown not to be very effective. Only sex selection of spermatozoa by chromatin differences (cell sorting by flow cytometry) has demonstrated a significant enrichment of the X bearing sperm.

Chromosomes, Human, X↗
PubMed2000

Hormonal interactions in endometrial cancer.

Endometrial cancer (EC) is the most frequent malignant tumor of the female genital tract. Increasing evidence suggests that at least two different types of EC exist. Type I is associated with an endocrine milieu of estrogen predominance. These tumors are of endometrioid histology and develop from endometrial hyperplasia. They have a good prognosis and are sensitive to endocrine manipulation. Type II EC is not associated with a history of unopposed estrogens and develops from the atrophic endometrium of elderly women. They are of serous histology, have a poor prognosis, and do not react to endocrine manipulation. Both types of EC probably differ markedly with regard to the molecular mechanisms of malignant transformation. This article reviews reproductive and lifestyle factors modifying the risk of developing type I EC, including the use of hormonal contraceptives, hormone replacement therapy and tamoxifen. The roles of established and novel therapies for precancerous lesions and for invasive EC in the adjuvant and palliative settings are discussed.

Contraceptives, Oral, Hormonal↗
PubMed1997

Mutations in the human factor XII gene.

The factor XII gene from 31 unrelated factor XII-deficient patients from Germany, Switzerland, and Austria was screened for mutations at the genomic level. Several novel mutations were detected and their absence in a control group of 74 healthy unrelated individuals was checked. Most changes are in the serine protease domain affecting the catalytic triad His-393-Asp-442-Ser-544; two missense mutations, R398Q (arginine 398 to glutamine; gene bank accession no. U71276) and L395M (leucine 395 to methionine; gene bank accession no. U71277), are close to the active site histidine at position 393. Another mutation detected in a cross-reacting material (CRM)-positive female with a history of three abortions affects the active site aspartic acid by changing it to asparagine (D442N; gene bank accession no. U71275). The novel mutation G570R (glycine 570 to arginine; gene bank accession no. U71274) giving rise to a CRM-positive phenotype is located next to Cys571, which forms a vital disulfide bridge. Two mutations are causing reading frame shifts: one single basepair deletion in exon 12 [exon 12: 10590(DelC); gene bank accession no. U71278] and one acceptor splice site mutation [exon 14: 11397(G --> A); gene bank accession no. L43615]. The putative regulatory mutation exon 1:-8 (g --> c) in the upstream region of the gene is associated with an aberrant Taq I restriction site allele in intron B of the gene (gene bank accession no. X80393).

Alleles↗
PubMed1997

Segregation of sex chromosomes into sperm nuclei in a man with 47,XXY Klinefelter's karyotype: a FISH analysis.

Meiotic segregation of the sex chromosomes was analysed in sperm nuclei from a man with Klinefelter's karyotype by three-colour FISH. The X- and Y-specific DNA probes were co-hybridized with a probe specific for chromosome 1, thus allowing diploid and hyperhaploid spermatozoa to be distinguished. A total of 2206 sperm nuclei was examined; 958 cells contained an X chromosome, 1077 a Y chromosome. The ratio of X:Y bearing sperm differed significantly from the expected 1:1 ratio (chi2 = 6.96; 0.001 < P < 0.01). Sex-chromosomal hyperhaploidy was detected in 2.67% of the cells (1.22% XX, 1.36% XY, 0.09% YY) and a diploid constitution in 0.23%. Although the frequency of 24,YY sperm was similar to that detected in fertile males, the frequencies of 24,XX, 24,XY and diploid cells were significantly increased. A sex-chromosomal signal was missing in 4.26% of the spermatozoa. This percentage appeared to be too high to be attributed merely to nullisomy for the sex chromosomes and was considered, at least partially, to be the result of superposition of sex-chromosomal hybridization signals by autosomal signals in a number of sperm nuclei. The results contribute additional evidence that 47,XXY cells are able to complete meiosis and produce mature sperm nuclei.

Adult↗
PubMed1997

Pregnancy after intracytoplasmic sperm injection with sperm from a man with a 47,XXY Klinefelter's karyotype.

OBJECTIVE: To report the initiation of a pregnancy that was achieved by intracytoplasmic sperm injection (ICSI) with sperm from a patient with Klinefelter's syndrome. DESIGN: Case report. SETTING: University women's hospital IVF center. PATIENT(S): A couple with primary infertility and nonmosaic 47,XXY karyotype of the male partner. INTERVENTION(S): Intracytoplasmic sperm injection after ovarian stimulation and transvaginal ultrasound-guided oocyte pick-up with sperm from a hypergonadotropic man with a nonmosaic 47,XXY karyotype. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S): Despite a 47,XXY karyotype in all 50 analyzed lymphocyte metaphases, the sperm of the patient led to a clinical pregnancy with the first attempt of ICSI and intrauterine transfer of three embryos. The pregnancy stopped developing in the ninth week. Cytogenetic investigation of the abortion material revealed a numerical normal 46,XXY karyotype. CONCLUSION(S): Sperm from a patient with hypergonadotropic nonmosaic Klinefelter's syndrome, when used for ICSI, can lead to a pregnancy.

Abortion, Induced↗
PubMed1997

Relevance of genetic counselling in couples prior to intracytoplasmic sperm injection.

Since the first reports of successful pregnancies after treatment with intracytoplasmic sperm injection (ICSI) in humans numerous attempts have been made to assess the genetic risks of this highly invasive technique. During the study period (February 1995-November 96), 142 couples were referred to our genetic counselling unit prior to ICSI. In three couples, genetic counselling revealed a high recurrence risk for a monogenic disease (myotonic dystrophy, hereditary ataxia and polycystic kidney disease). In nine out of 128 men (7%) an abnormal karyotype was identified, including three Robertsonian translocations, two reciprocal translocations, three sex chromosome aberrations and one case with centric fission of chromosome no. 7. A total of 14 men refused chromosomal analysis. Only one of the 122 women examined had an abnormal karyotype (47, XXX). Five out of six men with congenital bilateral absence of the vas deferens (CBAVD) had at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Three had mutations in both CFTR alleles, including one case in which the second mutation was the 5T allele. One patient with CBAVD and a single Delta F508 CFTR mutation also had left renal agenesis. In conclusion, we strongly recommend that genetic counselling, chromosomal analysis and, in the case of CBAVD, screening for CFTR mutations should be offered to all couples with a diagnosis of male or idiopathic infertility.

Adult↗
PubMed1997

Management of involuntary childlessness.

Any definition of involuntary childlessness has to consider the difference between sterility and subfertility. As the latter affects about 20-30% of all couples at least once in their lives, general practitioners (GPs) may be the first to be confronted with this problem. This review presents the most relevant diagnostic and therapeutic options in cases of female or male infertility, and discusses the new assisted reproductive technologies (such as insemination, in vitro fertilization, gamete transfer and intracytoplasmatic sperm injection) so that GPs may adequately inform their patients about these procedures and their risks and outcomes. Although controversial, involuntary childlessness and its clinical treatment seem to have a strong psychological impact on a couple's social, emotional and sexual life. Being available for discussion with childless couples and offering ongoing support may be the most important role for the GP in this context.

Family Practice↗
PubMed1996

The corpus luteum insufficiency: a multifactorial disease.

The pulsatile release pattern of LH during the entire menstrual cycle is well defined; however, the response of corpora lutea to these LH pulses in patients suffering from corpus luteum insufficiencies (CLI) is largely unknown. Patients suffering from CLI were selected from infertile patients on the basis of low progesterone (P < 25 nmol/L) in a blood sample withdrawn during a monitoring cycle. During the next cycle, nine blood samples were collected during the follicular and luteal phase and follicular development was assessed by vaginal sonography. Of 109 patients who had a CLI in the monitoring cycle, 55 had a CLI again, and 38 women agreed to undergo assessment of pulsatile hormone secretion. These women again had P < 25 nmol/L at days 6 and 7 of the luteal phase and blood samples were withdrawn through antecubital vein catheters from 0900-1700 h at 10-min intervals on days 7, 8, or 9 following ovulation. From 38 patients with such defined CLI, 16 (42%) had no LH episode and significantly lower basal LH levels in comparison with 14 control subjects. Thirteen (34%) of the patients had normal appearing LH episodes despite too low P and E2 concentrations, but their CL did not react to the LH episodes. The remaining 9 patients (24%) had normal LH episodes; their CL reacted to these episodes, but their basal P levels were too low. In all blood samples LH was not only determined using an immunoassay but also by the mouse Leydig cell testosterone production bioassay. It could be established that no CLI exists, which is due to the release of bioinactive LH. It is anticipated that the differentiation of three different types of CLI, one of hypothalamic and two of ovarian origin, may allow the development of differential diagnostic and therapeutic tools in the future.

Adult↗