Simultaneous dacryocystography and dacryoscintigraphy using SPECT/CT in the diagnosis of nasolacrimal duct obstruction

Epiphora, an abnormal overflow of tears, is commonly caused by tear drainage system anomalies including nasolacrimal duct obstruction. To assess morphologic abnormalities, dacryocystography by CT is used when CT contrast material is syringed into the lacrimal drainage system. To evaluate the function of the system, dacryoscintigraphy is the most readily available noninvasive method. In the case presented, a 43-year-old man was referred to our clinic with an 8 months' history of indefinite left side epiphora. After performing dacryoscintigraphy, we acquired SPECT/CT images during dacryocystography by CT to establish the surgical indication.     

Inhibition of growth of experimental human endometrial cancer by an antagonist of growth hormone-releasing hormone

Antagonists of GHRH are being developed for the treatment of various cancers. In this study we investigated in vivo and in vitro the effects of the GHRH antagonist MZ-J-7-118 and its mechanism of action in HEC-1A human endometrial cancer. Treatment of nude mice bearing HEC-1A xenografts with 10 mug/d MZ-J-7-118 for 6 wk significantly inhibited the volume of HEC-1A tumors by 43%, tumor weight by 40% compared with controls and prolonged the tumor doubling time from 18.7 +/- 1.4 to 25.4 +/- 3.8 d. Administration of 20 mug MZ-J-7-118, sc, twice a day significantly (P < 0.05) decreased HEC-1A growth, as evidenced by a 57.9% decrease in tumor volume, a 50.7% reduction in tumor weight, and the extension of tumor doubling time from 17.5 +/- 2.8 to 36.4 +/- 6.5 d. Therapy with GHRH antagonists significantly decreased serum IGF-I levels in experiment 1, and significantly increased tumoral IGF-I levels in experiment 2 in treated mice. Levels of IGF-II and vascular endothelial growth factor-A in tumors were not changed. Specific high affinity binding sites for GHRH were found on HEC-1A tumor membranes using ligand competition assays with (125)I-labeled GHRH antagonist JV-1-42. MZ-J-7-118 displaced radiolabeled JV-1-42 with an IC(50) of 0.13 +/- 0.04 nm. The expression of mRNA for GHRH and splice variants of the GHRH receptor in HEC-1A tumors was demonstrated by real-time RT-PCR analysis. HEC-1A cells cultured in vitro secreted GHRH into the medium. The GHRH antagonist MZ-J-7-118 inhibited the growth of HEC-1A cells in vitro. Our results indicate that GHRH antagonists can reduce the growth of human endometrial cancer and could be used as an alternative adjuvant therapy for the management of endometrial cancer.     

Expression of a splice variant of the receptor for GHRH in 3T3 fibroblasts activates cell proliferation responses to GHRH analogs

The stimulatory effects of growth hormone-releasing hormone (GHRH) and the antiproliferative action of GHRH antagonists have been demonstrated in various cancers, but the receptors that mediate these responses are not clearly identified. Recently, we reported that human cancer cell lines express splice variants (SVs) of the receptors for GHRH. SV1 exhibits the greatest similarity to the pituitary GHRH receptor and is most likely to be functional. To ascertain whether SV1 mediates mitogenic effects on nonpituitary tissues, we expressed SV1 in 3T3 mouse fibroblasts and studied the properties of the transfected cells. Radioligand binding assays with (125)I-labeled GHRH antagonist JV-1-42 detected high affinity (K(d) = 0.58 +/- 0.17 nM) binding sites for GHRH with a maximal binding capacity (B(max)) of 103 +/- 17.4 fmol/mg of membrane protein in 3T3 cells transfected with pcDNA3-SV1, whereas the control cells transfected with the empty vector did not show any GHRH binding. Cell proliferation studies showed that cells expressing SV1 are much more sensitive to GHRH analogs than the pcDNA3 controls. Thus, the expression of SV1 augments the stimulatory responses to GHRH(1-29)NH(2) or GHRH agonist JI-38 and inhibitory responses to GHRH antagonist JV-1-38 as compared with pcDNA3 controls. The stimulation of SV1-expressing cells by GHRH or JI-38 is followed by an increase in cAMP production, but no GH release occurs. Vasoactive intestinal peptide had no effect, and its antagonist JV-1-53 did not inhibit the proliferation of SV1-expressing cells stimulated by GHRH. Our results suggest that SV1 could mediate responses of nonpituitary cells and various tumors to GHRH and GHRH antagonists. The presence of SV1 in several human cancer cell lines provides a rationale for antitumor therapy based on the blockade of this receptor by specific GHRH antagonists.     

Menstrual regulation by intramuscular injections of 16-phenoxy-tetranor PGE2 methyl sulfonylamide or vacuum aspiration. A randomized multicentre study

Summary. A multicentre trial was conducted to compare the efficacy and side-effects of an intramuscularly administered PGE₂ analogue and vacuum aspiration in women with a delay of up to 21 days in the expected onset of menses. A total of 473 such women were randomly allocated to treatment with either 16-phenoxy-W-17, 18, 19, 20-tetranor PGE₂ methyl sulfonylamide (three intramuscular injections of 0.5 mg at 3-h intervals) or vacuum aspiration, and the outcome of therapy assessed 1, 2 and 6–8 weeks later. Retrospective analysis of hCG levels indicated that 419 (88.6%) women had been pregnant at the time of treatment. With few exceptions, administration of the PGE₂ analogue induced vaginal bleeding in both pregnant and non-pregnant women but the duration and subjectively perceived amount of bleeding were greater than after vacuum aspiration. Both treatments were equally effective. In pregnant women the overall frequency of complete abortion was 91% for prostaglandin treatment and 94% for vacuum aspiration. If non-pregnant women were included, the respective success rates (i.e. percentages of women not pregnant 2 weeks after treatment) were 92% and 95%. Gastrointestinal side-effects and lower abdominal pain requiring intramuscular analgesia were more common after prostaglandin therapy than following vacuum aspiration in both pregnant and non-pregnant women.