Developmental study of androgen responsiveness in the submandibular gland of the mouse.

The development of androgen responsiveness in the submandibular gland of normal and androgen-resistant (Tfm) mice of different ages was studied after varying hormonal treatments. Total esteroproteolytic (tamase) activity of submandibular gland homogenates was used as a marker for androgen action. Newborn mice of all four genotypes (normal male, normal female, carrier Tfm females, and Tfm males) were resistant to androgen. However, at 3 weeks of age the capacity to develop a tamase response appears in normal and carrier Tfm animals given androgen and rapidly rise to maximal levels. The level in the normal animal is regulated thereafter primarly by the level of circulating androgen. In contrast, the tamase response in the Tfm male of all ages and under all androgen regimens was minimal.     

Expression of stem-cell factor and its receptor c-kit protein in normal testicular tissue and malignant germ-cell tumours

The proto-oncogene c-kit and its ligand stemcell factor (SCF) may play an important role in the development of normal and malignant testicular tissue. This study investigates the presence of SCF and c-kit protein in 32 orchiectomy specimens of patients with testicular cancer, in 5 specimens of normal testicular tissue and in three established non-seminomatous germ-cell cancer cell lines (H12.1, H32, 577ML) by an immunohistochemical approach. Out of 9 testicular cancer specimens classified as pure seminomas, 7 (78%) showed a strong immunohistochemical reaction for both SCF and c-kit protein on the surface of the tumour cells. Fourteen non-seminomatous germ-cell tumours composed of embryonal carcinoma were completely negative for both SCF and c-kit protein and only faint positivity was found in 6 tumours (26%). Differentiated teratomatous structures within the specimens of nonseminomatous tumours showed a strong immunohistochemical reaction for SCF and c-kit protein in 8 of 11 (73%) cases. All three testicular cancer cell lines showed only faint staining reactions for c-kit protein and none for SCF. No secretion of SCF by the three lines in vitro was detected. The addition of high concentrations of SCF (100 ng/ml) to the testicular cancer cell lines in culture conditions without fetal calf serum resulted in a 1.4 to 3-fold growth stimulation compared to cell growth in serum-free medium alone. This effect was not detectable when the cells were cultured in serum-containing media. In the normal testicular tissue the germ-cells displayed a strong immunohistochemical reaction for c-kit protein while SCF positivity was found at the tubular membrane and on the surface of Sertoli cells. The SCF/c-kit system may possess a regulatory function in normal testicular tissue by possibly providing the microenvironment necessary for spermatogenesis. With the development of testicular cancer, this regulatory system seems to be lost, particularly in non-seminomatous germ-cell tumours. A growthstimulatory effect of high concentrations of SCF on nonseminomatous testicular cancer cell lines can be detected only in culture conditions with serum-free media. The effects achievable by the combination of SCF with other growth factors need to be further studied, as well as the role of the c-kit/SCF regulatory system for normal spermatogenesis and its possible implications for the understanding and treatment of male infertility.     

Physiological, biochemical, and morphological characteristics of myocardial anoxia: the use of a semi-perfusion canine preparation

Regional myocardial anoxia was produced in dogs by perfusion of the left circumflex artery (LCA) with deoxygenated blood. Isolated sarcoplasmic reticulum fragments (cardiac relaxing system) showed decreased Ca2+ binding and uptake. The ability of isolated mitochondria to utilise long-chain fatty acids was markedly reduced. This model has revealed inherent biochemical differences between ischaemia and anoxia.     

Factors determining improvement in left ventricular function after reperfusion therapy for acute myocardial infarction: primacy of baseline ejection fraction

Improvement in left ventricular ejection fraction is a measure of salvage of ischemic myocardium after reperfusion therapy for acute myocardial infarction. The degree of improvement in left ventricular ejection fraction may be influenced by many factors. Therefore, 137 patients in whom paired radionuclide angiograms were obtained within 24 h of acute infarction and before hospital discharge were retrospectively evaluated to determine which factors most affect improvement in ejection fraction. Only baseline ejection fraction correlated significantly with improvement in ejection fraction by both univariate analysis (ejection fraction as a continuous variable; p less than 0.001; ejection fraction as a categorical variable, less than or equal to 45% versus greater than 45%, p less than 0.0001) and multivariate analysis (p less than 0.0001). Reperfusion status (patent versus occluded infarct artery) and extent of coronary artery disease (one, two or three vessel) were significant factors by multivariate but not by univariate analysis. Location of infarction, treatment modality and time to treatment did not correlate with change in ejection fraction by either statistical technique. Thus, of those factors tested, baseline left ventricular ejection fraction is the most potent predictor of improvement in ventricular function after acute infarction. Knowledge of baseline ejection fraction may be helpful in deciding whether to treat some patients with equivocal indications or contraindications for reperfusion therapy. Clinical trials of reperfusion strategies should stratify patients on the basis of baseline ejection fraction if ejection fraction is to be used as an end point for myocardial salvage.     

De novo Carcinoma of the Rectum: A Case Report

There is strong evidence in the literature to suggest that most of the colorectal carcinomas arise from adenomatous polyps. Yet, rare carcinomas may arise de novo and we are reporting such a case of intramucosal rectal carcinoma occurring in a 47-year-old healthy man.     

Serum thrombopoietin levels in patients with aplastic anaemia

Endogenous serum thrombopoietin (TPO) levels were measured in 31 patients with aplastic anaemia (AA) using an enzyme immunoassay with a sensitivity of 20 pg/ml. The median platelet count for all AA patients was 30 ± 29 × 10⁹/l (range 5–102) compared with a median of 284 ± 59 × 10⁹/l (range 148–538) for normal controls. Serum TPO levels were significantly elevated in all patients compared with normals (1706 ± 1114.2, range 375–5000 v 78 ± 54, range 16.5–312.9, P  < 0.0001). There was no correlation between serum TPO levels and the degree of thrombocytopenia in AA patients, but TPO levels were significantly higher in patients who were platelet transfusion dependent than in patients who were transfusion independent ( P  < 0.01). There was a trend for higher TPO levels in patients with severe AA compared with non-severe AA patients. Clinical trials of TPO and a related truncated, pegylated molecule, megakaryocyte growth and development factor (PEG-rHuMGDF), are awaited to determine whether treatment with these drugs will result in increased platelet counts in patients with AA.     

Balloon coarctation angioplasty in adolescents and adults: early and intermediate results.

Twenty-three adolescent and adult patients with native coarctation of the aorta underwent balloon dilatation. Dissection of the aorta developed in one patient. Data were collected on the remaining 22 patients. They ranged in age from 15 to 55 years (mean 23 +/- 9.2 years). Invasive measurement of the peak systolic gradient (PSG) and biplane angiography were performed before and immediately after angioplasty and at follow-up 4 to 48 months (mean 15 months) later. PSG before dilatation was 37 to 100 mm Hg (mean 66.9 +/- 19.9 mm Hg) and decreased to 0 to 30 mm Hg (mean 9.1 +/- 11 mm Hg) immediately after dilatation (p less than 0.001). Restenosis occurred in two patients 6 months after dilatation, and one patient had an incomplete dilatation. These three patients underwent successful redilatation and remained improved 12 to 19 months later. There was no significant change in gradient at repeat catheterization in the remaining 20 patients. PSG was 0 to 20 mm Hg (mean 5.8 +/- 7.2 mm Hg). Angiography showed that a small aneurysm developed in one patient immediately after dilatation and in another 6 months later. Eleven patients were restudied more than once, and no change in gradient or size of the aneurysm was noted at mean follow-up 25 months after dilatation. This study demonstrated that balloon angioplasty is an effective method of treating adolescent and adult patient with native coarctation of the aorta. However, because of the uncertain natural history of aneurysm after dilatation, this procedure should be considered investigational until much longer follow-up times are available.