EFFECTS OF NORGESTREL AND ETHINYLOESTRADIOL INGESTION ON SERUM LEVELS OF SEX HORMONES AND GONADOTROPHINS IN MEN

DL-norgestrel and ethinyloestradiol were ingested separately and in combination by six healthy men. Serum levels of testosterone, 5α-dihydrotestosterone, oestradiol, FSH, LH and prolactin were measured before (basal), during and after ingestion of the combined drugs. Ethinyloestradiol 50 μg and DL-norgestrel 500 μg for nine days lowered the levels of testosterone to 8% (1·25 nmol/l = 0·36 ng/ml), 5α-dihydrotestosterone to 22% (0·39 nmol= 106 pg/ml), oestradiol to 46%(0·025 nmol/l = 6·88 pg/ml), FSH to 31% (0·55 U/l)and LH to 61% (2·37 U/l) of the basal values. All levels had risen on the third day after stopping the drugs and had recovered to pretreatment values within a week. Prolactin values did not show any definite trend of change during the treatment. In three men ethinyloestradiol alone, 50 μg daily for 5 days, reduced serum levels of all three sex hormones to approximately 80% of basal levels and FSH to 70% but left LH and prolactin levels unchanged. In three men DL-norgestrel alone, 525 ug daily for 4 days, reduced the androgen levels to below 40% of the basal levels, but had little effect on oestradiol levels. FSH, LH and prolactin levels were reduced to 63%, 70% and 65% respectively by the 4 days of DL-norgestrel treatment. The 26 h effects of DL-norgestrel were studied in three men who ingested 1050 ug of the drug in one dose. Serum testosterone and 5α-dihydrotestosterone levels had their greatest depression (30% and 60% respectively) at 12 to 14 h after the ingestion, whereas serum levels of DL-norgestrel peaked at 2 h after the ingestion. In this study serum FSH levels showed a clear depression in two men but LH and prolactin levels did not change. The results show a powerful effect of DL-norgestrel in reducing serum androgen levels in men, an effect which may be partly mediated through the concurrent suppression of the pituitary gonadotrophins.     

Origin of Pulmonary Megakaryocytes

1. Evidence is presented which indicates that pulmonary megakaryocytesdo not originate in the lungs but elsewhere in the body and are carried tothe lungs in the venous blood.

2. Some megakaryocytes in the lungs evidently deliver platelets to theblood.

3. Surgery is a potent stimulus to megakaryocyte production; the numbersof megakaryocytes found in the lung postoperatively is significantly increased.

Submitted on July 3, 1964 Accepted on September 19, 1964     

Circulating Megakaryocytes and Platelet Release in the Lung

1. Megakaryocytes were demonstrated in central venous blood of each of23 patients who underwent cardiac catheterization. Cell counts ranged from0.7 to 5.9 megakaryocytes per ml. of blood; the equivalent of one-third ofthese cells were considered to contain a full complement of cytoplasm. It hasbecome evident that megakaryocytes are normal constituents of blood.

2. In an attempt to quantify megakaryocyte migration from the bone marrow it was calculated that from 20-50 per cent of the mature megakaryocytepopulation enters the blood and ultimately reaches the lungs. The possibilitythat all megakaryocytes migrate from the marrow is not precluded with certainty by these studies.

3. It was estimated that from 7-17 per cent of the body’s platelets are released in the pulmonary capillaries. If all megakaryocytes migrate from thebone marrow, then as much as 33 per cent of the platelet population is delivered to the blood in the lungs.

Submitted on January 15, 1965 Accepted on March 13, 1965     

GONADAL FUNCTION IN BLOOM''S SYNDROME

Five patients with Bloom's syndrome aged from 2 8/12 to 27 years, all of whom had hypogonadism, were subjected to an i.v. LHRH test and two of them to an i.m. HCG test. There was increased responsiveness of plasma LH and FSH, indicating that the hypogonadism is primary in nature and of early development. The tubular element of the testis seems to be mainly affected, as indicated by the particularly high FSH response to LHRH stimulation, a history of sterility in the two adult patients and documented azoospermia in one of them. The Leydig cells seem to be less affected and secrete sufficient androgens to enable puberty within acceptable normal limits. Hypogonadism seems to be a major characteristic of Bloom's syndrome.     

Effects of Adenosine Agonists on Intraocular Pressure and Aqueous Humor Dynamics in Cynomolgus Monkeys

The effects of single or multiple topical doses of the relatively selective A₁adenosine receptor agonists (R)-phenylisopropyladenosine (R-PIA) and N⁶-cyclohexyladenosine (CHA) on intraocular pressure (IOP), aqueous humor flow (AHF) and outflow facility were investigated in ocular normotensive cynomolgus monkeys. IOP and AHF were determined, under ketamine anesthesia, by Goldmann applanation tonometry and fluorophotometry, respectively. Total outflow facility was determined by anterior chamber perfusion under pentobarbital anesthesia. A single unilateral topical application of R-PIA (20–250 μg) or CHA (20–500 μg) produced ocular hypertension (maximum rise=4.9 or 3.5 mmHg) within 30 min, followed by ocular hypotension (maximum fall=2.1 or 3.6 mmHg) from 2–6 hr. The relatively selective adenosine A₂antagonist 3,7-dimethyl-1-propargylxanthine (DMPX, 320 μg) inhibited the early hypertension, without influencing the hypotension. Neither 100 μg R-PIA nor 500 μg CHA clearly altered AHF. Total outflow facility was increased by 71% 3 hr after 100 μg R-PIA. In conclusion, the early ocular hypertension produced by topical adenosine agonists in cynomolgus monkeys is associated with the activation of adenosine A₂receptors, while the subsequent hypotension appears to be mediated by adenosine A₁receptors and results primarily from increased outflow facility.     

Computer-generated three-dimensional reconstructions of serially sectioned mouse embryos

We have been involved with a group of computer scientists and anatomists in the development of computer-based methodologies that not only combine the advantages of scanning electron microscopy and conventional histology, but provide the additional dimension of tissue recognition. The latter is achieved by the appropriate labelling of tissues and structures by delineation or ‘painting’. Individually segmented anatomically defined tissues can be highlighted in a particular colour and viewed either in isolation or in combination with other appropriately labelled tissues and organs. Tissues can be shown in any orientation either as a transparent overlay on computer-generated histological sections or as 3-D images without the histological background. An additional feature of the system is that computer graphics technology combined with 3-D glasses now also allows the viewer to see the object under analysis in stereo. This facility has been found to be particularly helpful in drawing attention to topological relationships that had not previously been readily noted. As the mouse is now the mammalian model of choice in many areas of developmental research, it is of critical importance that a basic level of skill is available in the research community in the interpretation of serially sectioned material, for example, for the rapidly expanding field in which gene expression studies play a significant role. It is equally important that there is an understanding of the dynamic changes that occur in relation to the differentiation of the various organ systems seen in these early stages of development. What we emphasise here is the additional information that it is possible to gain from the use of this tool which, in our view, could not readily have been gained from the analysis of scanning electron micrographs or by studying conventional serial histological sections of similar stages of mouse embryonic development. The methodology has been developed as part of a large project to prepare a database of mouse developmental anatomy covering all stages from fertilisation to birth in order to allow the accurate spatial mapping of gene expression and cell lineage data onto the digital Atlas of normal mouse development. In this paper we show how this digital anatomical Atlas also represents a valuable teaching aid and research tool in anatomy.     

Nasal resistance—a reliable assessment of nasal patency?

This study was undertaken to determine the distribution of nasal resistance in a healthy white population. One hundred subjects without nasal complaints were selected for the investigation. The test subjects were divided into two groups on the basis of anterior rhinoscopy. Group 1 included 60 subjects with rhinoscopically normal noses. Group 2 included 40 subjects with rhinoscopically abnormal noses. The pressure-flow data were recorded via active anterior mask rhinomanometry. The analogue pressure and flow signals were sampled and digitized by a computer system according to the time averaging method. Nasal resistance was calculated according to the recommendations of the International Committee on Standardization of Rhinomanometry. The normality of unilateral nasal resistance data distributions was assessed by the Kolmogorov-Smirnov Goodness of Fit Test at inspiratory and expiratory corresponding pressures of 50 Pa, 75 Pa, 100 Pa, and 150 Pa. The distributions of the calculated total resistance data were estimated at inspiratory and expiratory reference pressures of 75 Pa and 100 Pa. The data distributions of the two groups were compared using the Mann-Whitney U-test. Distributions for unilateral resistance were frequently found to deviate from normality. The distributions of total nasal resistance data never showed significant deviation from normality. More non-normal distributions were observed in Group 2 than in Group 1. Significant differences were determined between the two sub-groups for the non-decongested data. The entire group of subjects was homogeneous for the decongested data. The subjective assessment of nasal patency appeared not to be a sufficient criterion for the selection of subjects for normative studies in rhinomanometry. The presence of anatomical abnormalities and the influence of the nasal cycle could be responsible for the skewness of nasal resistance data in the normative studies in rhinomanometry.