Bone morphogenetic protein 6 promotes FSH receptor and anti-Müllerian hormone mRNA expression in granulosa cells from hen prehierarchal follicles.

A growing body of literature provides evidence of a prominent role for bone morphogenetic proteins (BMPs) in regulating various stages of ovarian follicle development. Several actions for BMP6 have been previously reported in the hen ovary, yet only within postselection (preovulatory) follicles. The initial hypothesis tested herein is that BMP6 increases FSH receptor (FSHR) mRNA expression within the granulosa layer of prehierarchal (6-8 mm) follicles (6-8 GC). BMP6 mRNA is expressed at higher levels within undifferentiated (1-8 mm) follicles compared with selected (≥9 mm) follicles. Recombinant human (rh) BMP6 initiates SMAD1, 5, 8 signaling in cultured 6-8 GC and promotes FSHR mRNA expression in a dose-related fashion. In addition, a 21 h preculture with rhBMP6 followed by a 3 h challenge with FSH increases cAMP accumulation, STAR (StAR) expression, and progesterone production. Interestingly, rhBMP6 also increases expression of anti-Müllerian hormone (AMH) mRNA in cultured 6-8 GC. This related BMP family member has previously been implicated in negatively regulating FSH responsiveness during follicle development. Considering these data, we propose that among the paracrine and/or autocrine actions of BMP6 within prehierarchal follicles is the maintenance of both FSHR and AMH mRNA expression. We predict that before follicle selection, one action of AMH within granulosa cells from 6 to 8 mm follicles is to help suppress FSHR signaling and prevent premature granulosa cell differentiation. At the time of selection, we speculate that the yet undefined signal directly responsible for selection initiates FSH responsiveness. As a result, FSH signaling suppresses AMH expression and initiates the differentiation of granulosa within the selected follicle.

Gonadotrophin-inhibitory hormone receptor expression in the chicken pituitary gland: potential influence of sexual maturation and ovarian steroids.

Gonadotrophin-inhibitory hormone (GnIH), a hypothalamic RFamide, has been found to inhibit gonadotrophin secretion from the anterior pituitary gland originally in birds and, subsequently, in mammalian species. The gene encoding a transmembrane receptor for GnIH (GnIHR) was recently identified in the brain, pituitary gland and gonads of song bird, chicken and Japanese quail. The objectives of the present study are to characterise the expression of GnIHR mRNA and protein in the chicken pituitary gland, and to determine whether sexual maturation and gonadal steroids influence pituitary GnIHR mRNA abundance. GnIHR mRNA quantity was found to be significantly higher in diencephalon compared to either anterior pituitary gland or ovaries. GnIHR mRNA quantity was significantly higher in the pituitaries of sexually immature chickens relative to sexually mature chickens. Oestradiol or a combination of oestradiol and progesterone treatment caused a significant decrease in pituitary GnIHR mRNA quantity relative to vehicle controls. GnIHR-immunoreactive (ir) cells were identified in the chicken pituitary gland cephalic and caudal lobes. Furthermore, GnIHR-ir cells were found to be colocalised with luteinising hormone (LH)beta mRNA-, or follicle-stimulating hormone (FSH)beta mRNA-containing cells. GnIH treatment significantly decreased LH release from anterior pituitary gland slices collected from sexually immature, but not from sexually mature chickens. Taken together, GnIHR gene expression is possibly down regulated in response to a surge in circulating oestradiol and progesterone levels as the chicken undergoes sexual maturation to allow gonadotrophin secretion. Furthermore, GnIHR protein expressed in FSHbeta or LHbeta mRNA-containing cells is likely to mediate the inhibitory effect of GnIH on LH and FSH secretion.

Pyoderma gangrenosum associated with crohn disease: effect of TNF-alpha blockade with infliximab.

Eight patients with pyoderma gangrenosum associated with Crohn disease were treated with infliximab. All had active mucosal inflammation indicated by endoscopic examination. Within 1-4 months, infliximab treatment resulted in complete healing of the pyoderma gangrenosum in 3 cases (1 parastomal, 2 lower limb), partial healing in 3 (2 parastomal, 1 lower limb) and temporary improvement in 2. Adverse effects such as skin rash, pneumonia and diarrhoea were seen in three patients. Our results imply that infliximab has a therapeutic potential on skin manifestations associated with inflammatory bowel disease, even though successful treatment may require repeat courses of infliximab infusions.

On-demand treatment in patients with oesophagitis and reflux symptoms: comparison of lansoprazole and omeprazole.

BACKGROUND: There are few data on how patients on maintenance treatment of reflux oesophagitis take their medication. This study was designed to investigate the dosing patterns of patients on on-demand treatment and to compare lansoprazole with omeprazole in this regard. METHODS: Patients with reflux oesophagitis, initially treated until absence of symptoms, took capsules of either lansoprazole (30 mg) or omeprazole (20 mg) for 6 months; they were instructed to take the medication only when reflux symptoms occurred. In order to document dosing patterns, the medication was dispensed in bottles supplied with a Medication Event Monitoring System recording date and time the bottles were opened. There were regular follow-up visits with assessment of symptoms. RESULTS: Three-hundred patients were eligible for analysis according to 'all patients treated'. A dosing pattern was found of an increased intake mornings and evenings and constant intervals between intakes. Although there was no correlation between oesophagitis grade or initial symptoms and the amount of medication consumed, the patients had significantly fewer reflux symptoms the more medication they consumed. There was no difference in the number of capsules consumed between the lansoprazole (0.73 capsules/day) and omeprazole groups (0.71 capsules/day). Nor was there any difference between the groups in reflux symptoms during the course of the study. CONCLUSION: Despite rigorous instructions to take medication on demand, the results suggest that it is patient habits more so than symptoms that determine the frequency and interval of medication intake. Symptoms are not therefore decisive for the amount of medication consumed.

[Pseudomonas bacteremia developing after whirlpool bath]. / Pseudomonas-bakteriaemi opstået efter anvendelse af Spa-bad.

Whirlpools may be responsible for transmission of microbial infections among the bathers if the technical hygienic conditions in the care of the bath are not observed. Two cases of infection with Pneudomonas bacteria were observed after use of whirlpools in a deluxe summer chalet. On the basis of the documented cases, the necessity for specific requirements concerning the installation, running and control of whirlpools used commercially should be considered. In their advisory brochures, the responsible authorities should ensure that the requirements made concerning whirlpools should be intensified so that these baths in summer chalets which are rented out should be subject to public control. Owners and users of whirlpools should be aware of the importance of meticulous hygiene in their care.

Gastrointestinal lesions in hereditary hemorrhagic telangiectasia.

Gastrointestinal bleeding is the most frequent form of bleeding after epistaxis in patients with hereditary hemorrhagic telangiectasia. As a part of an epidemiologic study, gastrointestinal telangiectases could be endoscopically demonstrated in 28 patients with hereditary hemorrhagic telangiectasia, most frequently in the upper gastrointestinal tract and predominantly in the stomach and the duodenum. The typical endoscopic finding was nodular angiomas that did not differ, with regard to form and size, from external telangiectases. However, in 15 patients some of the gastrointestinal telangiectases were surrounded by an anemic halo. A significant difference was found in the age at onset of epistaxis (median 11 yr) and of gastrointestinal bleeding (median 55.5 yr). There was no intrafamilial or interfamilial variation as to heredity and clinical manifestations. The blood group distribution in patients with hereditary hemorrhagic telangiectasia and gastrointestinal telangiectases did not differ from that of other patients with hereditary hemorrhagic telangiectasia, whereas there was a significantly higher frequency of blood group O among patients with hereditary hemorrhagic telangiectasia than among the background population.

The use of indium-111-labelled platelets for scintigraphic localization of gastrointestinal bleeding, with special reference to occult bleeding.

Gamma-camera imaging of the abdomen after injection of autologous 111In-labelled platelets was applied for localization of gastrointestinal bleeding in a study of 22 patients. In 15 studies showing scintigraphic signs of bleeding, the clinical presentation included occult bleeding in 6, melaena in 4, and bloody stools in 5. Scintigraphy could be done repeatedly for up to 1 week after a single tracer injection. The time interval between the injection and scintigraphic visualization of bleeding ranged from 10 min to 68 h, being longest in cases of occult bleeding. In most cases the scintigraphic findings were supported by other diagnostic modalities, including surgical removal of presumed sources of bleeding. In seven studies without scintigraphic signs of bleeding a probable source of bleeding was identified by other means in one patient. The 111In-platelet method seems to be a promising method for localization of gastrointestinal bleeding which may prove particularly useful in cases of occult or recurrent bleeding.

Ranitidine and high-dose antacid in reflux oesophagitis. A randomized, placebo-controlled trial.

The liquid antacid Novaluzid (10 ml seven times daily) was compared with ranitidine (150 mg twice daily) and with placebo in 57 patients with symptoms and endoscopic signs of oesophagitis and gastro-oesophageal reflux. A randomized three-period change-over design with the double-dummy technique was used. Each treatment period lasted 6 weeks. Only 37 patients (64.9%) completed the entire trial. In retrospect, five patients receiving placebo were withdrawn because of insufficient effect, six patients because of side effects while taking Novaluzid and two while taking ranitidine. The remaining seven dropouts/withdrawals were for reasons without evident relationship to the treatment given. Statistical analyses based both on the 37 completers and on the 43 patients who had at least two treatment periods showed that ranitidine and Novaluzid were superior to placebo with regard to pain score (p less than 0.005) but not with regard to regurgitation, dysphagia, histology, and appearance on endoscopy (p greater than 0.05). It was impossible to distinguish statistically between ranitidine and Novaluzid. In conclusion, ranitidine and high-dose antacids are of equal effectiveness in the short-term treatment of reflux oesophagitis, and both are superior to placebo with regard to symptomatic relief.

Colonic transport of water and electrolytes in a patient with secretory diarrhea due to collagenous colitis.

Whole colon perfusion studies and measurements of luminal prostaglandin E2 were carried out in a 41-year-old female with collagenous colitis to investigate pathophysiological mechanisms for the diarrhea. Biopsies of the colorectal mucosa had revealed a continuous 25- to 60-micron subepithelial collagenous layer, but normal junctional complexes and capillaries. When the patient fasted, the diarrhea persisted and fecal electrolytes, as estimated from the concentration of sodium, potassium, and their anions, accounted for all the osmolality (284 mosm/kg) of stool water, the pH of which was above 8.0. The lumen-negative electrical potential difference in the rectum was -64 mV vs -45 +/- 2 mV (mean +/- SEM) in healthy controls. Profuse secretion of fluid and electrolytes occurred during colonic perfusion with saline. Transport of sodium appeared to be passive with flux ratios equal to those predicted for passive sodium movements, while chloride transport against a steep electrical gradient indicated active secretion. Perfusion with an "ileal output"-like solution decreased fluid and electrolyte secretion, suggesting that bicarbonate, in addition to chloride, may be a major determinant of secretion rates. Since immunoreactive prostaglandin E2 levels following in vivo equilibrium dialysis of feces ranged from 555 to 650 pg/ml vs 55 to 235 pg/ml (99% confidence limits) in healthy controls, it is speculated that prostaglandins synthesized locally in response to mucosal hypoxia might be the mediators of anion secretion.

Scintigraphic localization of intermittent gastrointestinal haemorrhage with indium-111-labelled platelets.

Because of the central role of blood platelets in haemostasis, 111In-labelled platelets might be supposed to participate in the haemostatic process and give rise to scintigraphic hot spots at the bleeding sites in cases of intermittent gastrointestinal haemorrhage. Three patients with intermittent gastrointestinal haemorrhage are described in whom focal tracer accumulations after injection of autologous 111In-labelled platelets indicated the presence of transient gastrointestinal haemorrhage. Repeatedly performed scintigraphy after injection of 111In-labelled platelets may prove to be a useful tool for the localization of intermittent gastrointestinal haemorrhage.

Relief of osteoporotic backache with fluoride, calcium, and calciferol.

In a prospective randomized clinical trial comprising 22 postmenopausal women with backache and a halisteretic spine with crush fracture(s), 12 women completed a 12-week therapy with sodium fluoride, calcium and calciferol and 10 with placebo. A statistically significant improvement (p less than 0.05), evaluated by a four-stage scale on pains, infirmity, and consumption of analgesics, was observed in the actively treated patients.

Suicide and attempted suicide in Greenland. A controlled study in Nuuk (Godthaab).

Suicidal behaviour in Eskimo populations has changed in pattern and quantity over the last decades. Rates have more than quadrupled and performers now are mainly young persons with obscure motivation. In a study from Greenland's major township all cases of attempted or completed suicide among Greenlanders are analysed for social, emotional, somatic, and environmental predisposing factors in comparison with a non-psychiatric, never-suicidal, matching group. Almost two per thousand of the adult population committed suicide yearly while attempts at suicide were five times as frequent. A quarrelsome, drinking, childhood home background was often found, at least as regards the attempters, who themselves frequently suffered from emotional conflicts with close contacts, alcohol affliction, criminality, and instability at work. Neither bereavement, cross-cultural exposure, broken homes, nor meteorological factors seemed to exert a significant influence. The results are discussed in relation to the social and cultural evolution of the Greenlandic society.

Treatment of painful osteoporosis with fluoride, calcium, and calciferol.

Fourteen women averaging 69.5 years of age with painful osteoporosis of the spine were treated with sodium fluoride, calcium salts and calciferol. At assessment after 5-19 months of therapy 8 patients were free of pains while in 5 women pains had decreased and mobility improved. One patient had unaltered pains. Side effects were few and mild.