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Introduction Fewer clinical trials are carried out in older people. It is unclear how representative and applicable clinical trials carried out exclusively in older people are. We compared clinical trials recruiting older people exclusively “older trials” to those recruiting adults of all ages “all age trials”, using anti-hypertensives acting on the renin-angiotensin aldosterone system (RAAS drugs) as an exemplar. Method We searched the US clinical trials register 1, to identify all trials carried out exclusively in those aged over 60. From these we selected trials of RAAS drugs. These were matched in a 2:1 ratio to trials carried out in adults of all ages. Data regarding baseline characteristics, adverse events and eligibility criteria were collected from clinical trial reports and clinicaltrials.gov. Estimated associations were calculated for age, sex and adverse events. Eligibility criteria were described and ICD- 10 coded, as appropriate. Results 71 clinical trials were carried out exclusively in older people.13 related to RAAS drugs. Participants in “Older trials” had higher mean age (73.1 and 55.9 respectively), mean difference 16.17 (CI 15.31–17.02). Older trials had fewer male participants. Participants in older trials had lower mean body mass index (BMI). A higher rate of participants in older trials experienced serious adverse events. (2.07, CI 1.55–2.75.) Few older trials had upper age limits (23.1% V 27% all age trials). All trials had exclusion criteria in multiple ICD blocks. Concurrent medications were a more common exclusion criterion in older trials (61.5% v 40.9%). Conclusions Clinical trials carried out exclusively in older people are representative in terms of age, serious adverse events and eligibility. Although there are multiple exclusion criteria for clinical trial participation in both groups, this is not prohibitive. This supports carrying out more trials exclusively in older people. References 1. NIH, US national library of medicine.ClinicalTrials.gov Available at https://clinicaltrials.gov/

Eight bitches presenting with vaginal discharges were diagnosed as having open pyometra, as assessed by ultrasonographic, radiographic, haematological and clinical investigation. Plasma progesterone was assessed before treatment with prostaglandin F2 alpha (Dinoprost) and three of the bitches had low concentrations. Each bitch was given multiple injections of PGF2 alpha and monitored during and after treatment. All bitches had basal progesterone concentrations after treatment and the uterine diameters were markedly reduced by that time. One bitch has subsequently produced a litter of seven pups. Five of six bitches that were subjected to ovariohysterectomy 1-2 months later had normal uteri, although one had caseated areas in the uterine wall.

An acute phase response has been identified during mid-gestation in bitches by determination of the serum C-reactive protein (CRP) concentration. In four pregnant bitches, a large increase in CRP during mid-gestation was followed by a second increase after parturition. In three pregnant bitches, a similar increase was observed during mid-gestation but the second (post parturition) increase was not detected. In two pregnant bitches only a small rise was observed in mid-gestation. No increase in CRP was observed in the serum of two bitches that were not mated following oestrus or in the serum of two bitches that were mated but did not become pregnant. One bitch was diagnosed as pregnant by palpation but did not produce a litter and did not have a mid-gestation increase in CRP. However, this animal did show an acute phase response shortly after oestrus.

Oocytes were collected from ovaries of bitches, at various stages of the oestrous cycle, after routine sterilization. Cumulus-enclosed oocytes were cultured for 0-72 h in a modified M-199 medium containing 10% oestrous bitch serum and 20 micrograms oestradiol ml-1. For oocytes surrounded by two or more layers of cumulus cells, an increase in the expression of mRNA transcripts for zona pellucida glycoprotein 3 (ZP3) was seen and reached peak levels after 48 h culture in vitro. Histological assessment showed that 39% of these oocytes had extruded their first polar body after 24 h culture in vitro. When these in vitro matured oocytes were transferred to oviduct cell monolayers and inseminated with fresh dog spermatozoa in Medium-199 supplemented with 10% fetal calf serum and 50 mg gentamicin sulfate ml-1, penetration of the zona pellucida started 1 h after insemination for oocytes that had been cultured for 48 and 72 h. At 12 h after insemination both male and female pronuclei were seen in 37.5% and 20% of the oocytes incubated for 48 and 72 h, respectively. No further development was seen.

Medroxyprogesterone acetate (MPA) was administered as a depot injection to two adult male dogs. One was injected with 75 mg as a depot injection once a month for 2 months and the other with 50 mg at 2-weekly intervals for 1 month, followed by 100 mg at 2-weekly intervals for a further 2 months. Two other male beagles were given gonadotrophin-releasing hormone (GnRH) agonists (nafarelin derivative no. 49947 and nafarelin acetate) at a dose of 50 micrograms day-1 for either 22 or 23 days. The profiles of luteinizing hormone (LH) and testosterone were monitored before and during the treatment periods, and changes in the dogs' testes, epididymides and prostate glands were determined post mortem. In the MPA-treated animals, LH was suppressed for only very brief periods. In contrast, in the dogs treated with GnRH agonist, LH and testosterone concentrations were suppressed for most of the treatment period. In the MPA-treated animals, histological changes were seen mainly in the head of the epididymis, and in the acrosome region of the spermatozoa still present in this region of the male reproductive tract. The acrosome, instead of being closely applied to the sperm head, was in contact only in the most anterior areas, with the remainder forming a fan-like projection, indicating increasing detachment from the sperm head. In the dogs treated with GnRH agonist there was clear evidence of cessation of normal spermatogenesis in most of the seminiferous tubules. Changes in the histology of the head of the epididymis were similar to (but more profound than) those found in the dogs treated with MPA. Seminal changes were demonstrated in ejaculates collected during the latter stages of the treatment period.

Real-time B-mode ultrasound imaging was carried out, using a scanner of moderate quality, on 40 fresh bitch cadavers to identify the presence of ovaries and significant ovarian structures. The results indicated that accurate identification of the ovaries depended on the presence of significant follicles or corpora lutea (CL). The findings were verified at post-mortem examination. The study was continued by scanning 35 live bitches using three different scanning units of increasingly improved quality to show that the process of ovulation could be assessed with reasonable accuracy with improved quality of equipment, although the exact fate of the follicle could not be imaged. The results were judged against assays for blood circulating progesterone. A final group of seven live bitches were scanned with a high-grade scanner using an annular phased-array transducer to attempt to image the process of ovulation. The non-echogenic follicle disappeared and was replaced by the CL that was hypoechoic with respect to surrounding tissue, thus allowing accurate assessment of the time of ovulation. This was confirmed by progesterone assay.

Using circulating plasma hormone estimations, ovulation was monitored in bitches. The results obtained indicate that the timing of ovulation bears little relationship to alterations in sexual behaviour. The bitches were killed and reproductive tracts were removed at various intervals after ovulation and ova or embryos were recovered. The embryo stages were assessed visually and some were investigated histologically. Embryonic development, to early blastocyst stage, took place within the oviducts during the first 12 days after ovulation and there was a marked increase in size between the early and late blastocyst. A culture system using cells from the uterine tube supported the development of one 1-cell embryo to the morula stage.

In a recent study of the efficacy of two methods of oestrous synchronisation in dairy heifers, progesterone profiles and ultrasound results showed that late embryonic/early foetal loss had a small but nevertheless important effect upon pregnancy rates (Logue & others 1991). Since some preliminary results were available which showed that the use of a 3 mg norgestomet ear implant alone, rather than in combination with a 3 mg norgestomet and 5 mg oestradiol valerate injection (Crestar Intervet UK Ltd), enhanced pregnancy rates in beef heifers (Favero & others 1989) and the technique was being used in Embryo transfer (ET) recipients (Broadbent pers com) it was felt that a further investigation of the technique was merited.

Urine samples were collected from 32 male dogs and examined for the presence of spermatozoa. Twenty-eight dogs were found to have spermatozoa in their urine, indicating that spermatogenesis is occurring normally.

Five pony mares were blood sampled during late pregnancy, foaling and early lactation. An homologous assay for horse prolactin was used to measure plasma prolactin concentrations in these samples. Regular estimates of cyclic activity were also made. Plasma prolactin concentrations rose markedly in the last week of pregnancy and remained high although variable in early lactation, before declining to basal levels by 1-2 months post partum. All mares showed a post-partum oestrus 7.0 +/- 0.9 days after parturition. One mare whose foal died shortly after birth showed a rapid decline in plasma prolactin values after death of the foal and an early oestrous period (4 days after parturition). The pattern of prolactin changes reported for the mare are in agreement with those reported for other mammalian species.

Results of preliminary investigations of fallopian tube patency in cattle using a method based on intrauterine instillation of PSP dye, and detection of the dye in the urine, suggest that this test can provide a useful diagnostic aid in cases of bilateral occlusion. In such cases PSP dye is not evident in the urine two hours later. In normal animals dye is present within 30 minutes. In two animals with unilateral blockage dye appeared at an intermediate time between the normal and bilaterally occluded cases. Repetition of the test and the use of adequate volumes of dye to cause uterine distension may be necessary to eliminate false negatives.

Canine semen was obtained by digital manipulation from two donor dogs and twelve stud dogs. The sperm-rich fraction was diluted with either of two different diluents and the survival of spermatozoa before and after freezing was determined. It appeared that there was no difference in the post-thaw survival rate in either of the diluents used.

The diagnosis of pyometra in the bitch was aided by radiographic examination of the abdomen and by a total white cell count. In cases of pyometra described, some uterine distension was seen on radiographic examination. A study was made of the course of blood urea levels as a guide to prognosis. High blood urea levels before operation may subsequently return to normal. The cases with poor prognosis were those in which the blood urea level rose steadily after ovarohysterectomy. Escherichia coli was found in almost all cases of pyometra, both closed and open. There was no evidence of a poorer prognosis in closed than in open cases of pyometra. Resume. Le diagnostic de la pyometrie chez la chienne fut facilite par l'examen radiographique de l'abdomen et par une numeration globulaire du total des leucocytes. Dam les cas de pyometrie decrits, on a vu une certaine dilatation uterine a l'examen radiographique. Une etude du cours des niveaux d'uree dans le sang fut faite a titre de guide pour le pronostic. Des niveaux eleves d'uree dans le sang avant l'operation peuvent redevenir normaux par la suite. Les cas avec un pronostic pauvre etaient ceux ou le niveaus d'uree dans le sang augmentait regulierement apres l'ovariectomie et l'hyterectomie. On trouva des E. coli dans presque tous les cas de pyomttrie aussi bien fermes qu'ouverts. Il n'y eut pas de preuves indiquant un pronostic plus pauvre dans les cas de pyometrie fermes que dans les cas ouverts. Zusammenfassung. Die Diagnose von Pyometra bei Hundinnen wurde durch die radiographische Untersuchung des Bauchraums und durch Bestimmung der weissen Gesamt-Blutkorperchenzahl unterstutzt. Bei den beschriebenen Fallen von Pyometra wurde rontgenologisch eine gewisse Vergrosserung der Gebarmutter beobachtet. Die Anderung des Harnstoff-gehalts des Bluts wurde als Anhalt fur die Prognose benutzt. Hohe Blutharnstoffkonzentrationen vor der Operation konnen anschliessend zuruckgehen. Die Falle mit schlechter Prognose waren diejenigen, in denen der Blutharnstoffgehalt nach der Ovarohysterectomie stetig anstieg. E. coli wurde in fast allen Fallen von Pyometra geschlossenen und offenen gefunden. Es gab keine Anzeichen fur eine schlechtere Prognose in geschlossenen Fallen von Pyometra im Vergleich mit offenen.

Summary. The uptake of 59Fe by rabbit placenta at different stages of gestation was determined, and subsequently the uptake of 59Fe by the subcellular fractions of the rabbit placenta during the last third of gestation was measured. The iron-containing compounds in the non-particulate fraction of the rabbit placenta during the last third of gestation were isolated and characterized.

THE desire to predetermine sex before conception and thus alter the natural sex ratio has led many investigators to seek methods of separating the populations of X- and Y-bearing sperm and over the past 50 years, a number of claims of success have been made. Ericsson et al.1 described a technique for the isolation of fractions rich in human Y sperm. On repeating the methods outlined in their paper, we were unable to find any evidence of enrichment of human Y sperm.

Behaviour, vaginal cytology and plasma progesterone concentrations were monitored during oestrus in a group of 6 beagle bitches before intrauterine insemination with frozen semen. At intervals after insemination, the reproductive tracts were examined for evidence of conception, which occurred in 5 of the bitches. One pregnant bitch had received treatment with stilboestrol before insemination.

Using a range of positive and negative sexual behaviour components, proceptivity of cycling, non-lactating mares and postpartum, lactating Pony mares was quantified around ovulation. Behavioural observations were compared to plasms concentrations of progesterone, total oestrogens and androstenedione. In addition, in cycling mares, comparison with plasma testosterone concentrations was carried out. Overall rejection behaviour by the mare was apparent both during dioestrus and during periods of basal plasma progesterone concentrations. Within cycling, non-lactating mares, and between postpartum ovulation associated with silent as opposed to overt oestrus, no consistent relationship existed between net behavioural scores and the circulating concentrations of oestrogens or androgens. The findings are taken to suggest that regulation of the signs of oestrus occurs to a large extent independently of circulating steroid concentrations.

Summary Six mares were studied over a period of two years under varying conditions of lighting from total darkness to normal ambient lighting. The mares continued to cycle during the winter under natural lighting and also when kept in total darkness. Circulating melatonin, progesterone and oestrogen concentrations were determined and related to clinical changes in the reproductive tract.

Plasma prolactin concentrations were measured in mares using an homologous radioimmunoassay. An annual rhythm in plasma prolactin was found, with concentrations higher during the summer than during the winter. In addition to this seasonal pattern, occasional high concentrations of prolactin were seen when concentrations were otherwise basal. Blood samples taken from mares during an oestrous cycle in October-November showed that prolactin values were basal for most of the cycle, with a marked rise in prolactin shortly before the onset of oestrus. This prolactin peak was associated with an increase in the size of the largest follicle, and with a peak of PGFM in some mares, but did not appear to be related to the LH surge. In oestrous cycles in March and May-June, there was a wide variation in the baseline of prolactin secretion, in accordance with the seasonal pattern already mentioned. However, the peak of prolactin seen around oestrus in October-November was less obvious in March and May-June. Post-partum mares showed a high but irregular profile of prolactin concentrations with no clear-cut pattern in relation to the oestrous cycle.

1. 1. The plasma clearance rates of 59Fe injected intravenously into sows is not increased as a result of pregnancy. 2. 2. The amount of iron transferred from sow to foetus during pregnancy is very small and represents less than 2 per cent of the iron injected into the mother. 3. 3. The pig placenta is able to synthesize ferritin. 4. 4. The haematology of the sow was normal whereas the foetus was anaemic as compared with other newborn animals. 5. 5. The results in the sow are compared with those obtained in the rabbit in which the foetuses have adequate iron stores at birth.