Treatment versus no treatment in chronic open angle glaucoma

In a controlled randomized study 15 patients (20 eyes) with chronic open angle glaucoma and visual field defects were followed by greater than 1 year, 12 of them were followed for 3 years. Half of the group were untreated controls, the other half treated with pressure reducing medical therapy. At least 5 consecutive computerized visual fields were recorded (COMPETER) on each eye, and the linear regression coefficient was calculated. With the reservation for uncontrolled compliance no significant difference in the line of favourable effect of pressure reduction could be spotted, in spite of an average pressure reduction in the treated group of 4 mmHg. More important than this result, which is open to criticism for the smallness of the material, uncontrolled compliance etc, is the lesson that a randomized experiment with treated and non-treated glaucoma cases carried out in accordance with the Helsingfors convention is hardly feasible.     

Differential diagnosis of early human pregnancies: impact of different diagnostic measures.

A total of 261 women in early pregnancy, either with mild symptoms of ectopic pregnancy (EP) or being at an increased risk for this condition, were included in a longitudinal study. The effectiveness of different diagnostic measures in obtaining correct final diagnoses was analyzed. In addition to clinical findings and symptoms, the use of serum human chorionic gonadotropin, serum progesterone, endovaginal sonography and a risk score for EP were all proven to be valuable in distinguishing normal intrauterine pregnancies from pathological pregnancies.     

Passive immunization of pregnant goats against ovine LH

Groups of three goats at 50, 90 and 130 days of gestation were passively immunized against ovine LH (oLH) by i.v. infusion of 8 ml serum equivalent of the immunoglobulin fraction of rabbit anti-oLH serum (LHAS). Goats at the same stages of gestation as above served as controls and received 8 ml serum equivalent of the immunoglobulin fraction of normal rabbit serum (NRS). Plasma concentrations of progesterone were determined by specific radioimmunoassay of blood collected at 20-min intervals from 6 h before infusion of LHAS or NRS to 12 h after infusion. Less frequent sampling was performed from 2 days before to 6 days after infusion. Plasma from all LHAS-immunized goats exhibited binding of oLH. Twelve hours after immunization, titres ranged from 1:135 to 1:215. All LHAS-treated goats had titres of less than 1:10 by 5 days after immunization, but a low level of oLH binding was still detectable. Treatment with LHAS or NRS did not shorten the length of gestation, with all goats delivering live offspring between 142 and 147 days after conception. Plasma concentrations of LH ranged from less than 0.15 micrograms/l to 4.8 micrograms/l and were greater than 0.15 micrograms/l in 181 of 255 samples (71%) for both the NRS-treated group, throughout the experiment, and the LHAS-treated groups before infusion of antiserum. Luteinizing hormone was not detectable in plasma samples obtained after LHAS infusion in goats at 50 or 130 days of pregnancy. Plasma concentrations of LH exceeded 0.15 micrograms/l in only five of 51 (10%) samples in 90-day-pregnant goats treated with LHAS, the maximum value reached being 0.80 micrograms/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

Advancing conservative treatment of ectopic pregnancy--laparoscopic and "non-surgical" management.

Improvements in diagnostic measures have contributed to the earlier diagnosis of ectopic pregnancy which in turn has led to the development of new and alternative methods of managing tubal pregnancies. Laparoscopic salpingotomy offers advantages such as a reduction in operating time and shorter hospital stays and convalescence as compared with conventional abdominal surgery. Furthermore, neither the frequency of persistent trophoblasts nor of second operations is increased, and the subsequent fertility rate is at least equal to that after laparotomy. "Non-surgical" treatment of ectopic pregnancy, such as systemic administration of methotrexate and laparoscopic/transvaginal ultrasonic--guided local injection of methotrexate, prostaglandins or hyperosmolar glucose, are attractive alternative methods in selected cases. These methods are safe and effective and have a high success rate and promising results for fertility. Laparoscopy is preferred to conventional abdominal surgery for the treatment of ectopic pregnancy. In selected cases, "non-surgical" treatment can be an attractive alternative therapy.     

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.      

bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors

Proliferative expansion and apoptotic cell death play prominent roles in T cell development. The molecular control of cell cycle progression and apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit apoptosis and slow cell cycle progression in cortical thymocytes and mature T cells, particularly during the transition from the quiescent state into the cell cycle. Here the impact of bcl-2 transgene expression on CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival of these progenitors at all of the four major differentiation stages, CD25- CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene we conclude that Bcl-2 inhibits proliferation only of T cell progenitors that are activated via the pre- TCR, not those stimulated via c-Kit and the IL-7 receptor.      

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.