Danazol administration after gonadotrophin-releasing hormone analogue reduces rebound of uterine myomas [published erratum appears in Hum Reprod 1998 Mar;13(3):780]

We report the results of administration of danazol after suspension of gonadotrophin-releasing hormone analogue (GnRHa) therapy for uterine myomas. A total of 21 women with uterine myomas was treated with 100 mg danazol for 6 months after GnRHa therapy. Uterine volume and endocrine status were monitored monthly by ultrasound and assay of plasma gonadotrophins, oestradiol and progesterone. The results show a rebound of uterine volume about 30% less than in controls at the end of danazol therapy. Menstrual cyclicity returned after 65 +/- 3 days in 16 subjects and five patients remained amenorrhoeic. Hormone assays confirmed renewed ovarian function in the women whose menstrual periods returned. Bone mineral content was substantially reduced during GnRHa treatment but improved significantly during danazol therapy even in the women who remained amenorrhoeic. These results show the utility of danazol in prolonging the therapeutic effects of GnRHa. The mechanism by which danazol inhibits rebound of uterine volume may be due to its antiprogesterone effects on uterine myomas.      

Using mark-recapture methodology to estimate the size of a population at risk for sexually transmitted diseases.

To study the spread of sexually transmitted diseases (STDs) using social/sexual mixing models, one must have quantitative information about sexual mixing. An unavoidable complication in gathering such information by survey is that members of the surveyed population will almost certainly have sexual contacts outside that population. The number of these outsiders may be substantial and, hence, important for the modelling process. In this paper, we develop a mark-recapture model for estimating the size of the population at risk for contracting a STD due to direct sexual contact with a specified population targeted by a survey. This mark-recapture methodology provides a reliable method of estimating the number of outsiders. Because not everyone in the targeted population may be sexually active, the size of the sexually active subset, used as the number marked in our tag-recapture formulation, must be estimated, which introduces extra variability. We derive an estimator of the variance of the estimated total number at risk that accounts for this extra variability and an expression for the bias of that estimator. We extend the methodology to stratified surveys and illustrate its use with data collected from a population of university undergraduates to estimate sexual mixing parameters of a deterministic model of the spread of STDs.     

Quantitative three-dimensional power Doppler ultrasound predicts the outcome of placental chorioangioma.

The relationship of large and vascularized chorioangiomas to adverse pregnancy outcome is well recognized. We present a patient with a large placental tumor and signs of impending fetal cardiac failure. The angioarchitecture of the tumor depicted by three-dimensional (3D) power Doppler ultrasound enabled us to accurately diagnose a placental chorioangioma. During the follow-up period, quantitative flow data obtained using 3D power Doppler indicated altered hemodynamics in the tumor and concomitant improvement in the condition of the fetus, enabling us to manage the mother conservatively. Spontaneous delivery occurred at 38 weeks without any complications. This report demonstrates the potential value of 3D power Doppler in prenatal diagnosis and monitoring of pregnancies complicated by large, vascularized chorioangioma.     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

Three-dimensional ultrasound diagnosis of Larsen syndrome with further characterization of neurological sequelae.

Larsen syndrome consists of skeletal dysplasia with multiple joint dislocations and a characteristic facies. The basis of this abnormality is a generalized mesenchymal disorder involving connective tissues. We describe our findings in a woman who was referred at 28 weeks' gestation due to multiple fetal anomalies suspected initially at an 18-week ultrasound examination. On three-dimensional (3D) ultrasound we found the fetus had bilateral genu recurvatum. Further 3D examination at 36 weeks confirmed the lower limb anomaly and revealed facial anomalies that led to the diagnosis of Larsen syndrome. An elective Cesarean section was performed at 38 weeks' gestation to minimize neurological sequelae. Magnetic resonance imaging was performed postnatally and showed pachygyria, colpocephaly and agenesis of the corpus callosum. In this case, 3D ultrasound facilitated the prenatal diagnosis of Larsen syndrome. A careful prenatal investigation for other associated anomalies such as those of the cardiovascular or neurological systems is warranted with this diagnosis. These associated lesions are likely to have a greater impact on prognosis than the classic symptoms of Larsen syndrome and a collaborative approach is necessary to optimize delivery and postnatal management of an affected fetus.     

Targeted gene disruption of murine CD7

CD7 is a 40 kDa type I transmembrane glycoprotein member of the Ig superfamily. CD7 is a marker of mature human T cells and NK cells, and is expressed early in their development. Cross-linking CD7 positively modulates T cell and NK cell activity as measured by calcium fluxes, expression of adhesion molecules, cytokine secretion and proliferation. CD7 associates directly with phosphoinositol 3'-kinase, and CD7 ligation induces production of D-3 phosphoinositides and tyrosine phosphorylation. Severe combined immunodeficiency has been associated with a lack of lymphocyte surface CD7. The CD7 ligand is unknown. The murine CD7 homolog is encoded by a single gene on chromosome 11. In order to characterize the role of CD7 in lymphocyte development and function we have eliminated the CD7 gene by targeted disruption. CD7- deficient mice display normal histology of thymus and spleen, normal lymphocyte populations in primary and secondary lymphoid tissues, and normal serum Ig levels. Specific antibody responses after immunization with T-dependent and T-independent antigens are equivalent in wild-type and CD7 knockout mice. CD7-deficient lymphocytes respond normally to T cell mitogenic and allogeneic stimuli, and display normal NK cell cytotoxicity.      

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.