Over a 7-year period, seminal analysis has been performed on 208 patients with testicular tumours, after orchiectomy, but before any other treatment. Only 22% of 54 patients with seminomas, and 29% of 154 patients with teratomas or mixed tumours, had sperm counts exceeding 10 million per ml. Very low sperm counts were observed in some patients who had previously fathered children. Post-treatment sperm counts were done in 117 patients, 80 of whom had received multiple drug chemotherapy: 42 of these men had pre- and post-treatment sperm counts. Overall, 24% of men receiving chemotherapy recovered sperm counts greater than 10 million per ml up to 3 years after therapy. Surprisingly, such recovery was seen in 35% of 23 men with initially poor sperm counts, but in only 26% of 19 with good initial counts. Only 27% of 49 patients with Hodgkin's disease had initial sperm counts of more than 10 million per ml; after chemotherapy only 1 of 29 patients recovered to this level. Only one quarter of these young men had semen which was adequate for cryopreservation. Artificial insemination with semen preserved in liquid nitrogen has been performed in 15 couples: 2 normal babies have been produced and a third pregnancy is progressing normally.

1 Receptor autoradiography using (-)- ['251]-cyanopindolol (CYP) was used to study the distribution of P-adrenoceptor subtypes in human right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium.2 The binding of(-)- ['251]-CYP to slide-mounted tissue sections ofhuman right atrial appendage was time-dependent (K, = 4.11 ± 1.01 x 10' M'minu', K-, = 1.47 ± 0.25 x 10-3min', n = 3), saturable (42.02 ± 2.96 pM, n = 4) and stereoselective with respect to the optical isomers of propranolol (pKD (-):8.97 ± 0.02, (+):6.88 ± 0.06, n = 3).3 The proportions of P-adrenoceptor subtypes were determined in slide-mounted tissue sections using the antagonists CGP20712A (P,-selective) and ICI 118,551 (f2-selective). In right atrial appendage and left ventricular papillary muscle 40% (34-45%) of the P-adrenoceptors were of the P2-subtype. were antagonized by CGP20712A (pKB = 9.29) suggesting an interaction with P,-adrenoceptors. Responses to procaterol were antagonized by ICI 118,551 (pKB = 9.06) suggesting an interaction at P2r adrenoceptors.6 The finding that a significant proportion of human myocardial adrenoceptors are ofthe p2-subtype has important clinical implications for the involvement of these receptors in the control of heart rate and force, and the autoradiographic evidence suggests other roles in the coronary vasculature and pericardium.

Receptor autoradiography with (−)‐[125 I]‐cyanopindolol (CYP) was used to study the distribution of β1 and β2‐adrenoceptor subtypes in the human internal mammary artery and saphenous vein. Images from X‐ray film and nuclear emulsion coated coverslips, exposed to [125 I]‐CYP labelled sections, showed a high density of β2‐adrenoceptors localized to the endothelium of the internal mammary artery and fewer β2‐adrenoceptors on the smooth muscle. The function of β‐adrenoceptors in ring preparations of the internal mammary artery was investigated in organ bath studies. (−)‐Isoprenaline produced concentration‐dependent relaxation of phenylephrine contracted rings. The potency and maximal effects of (−)‐isoprenaline were not influenced by the presence of the endothelium. Images of [125 I]‐CYP binding to the saphenous vein, from X‐ray film and nuclear emulsion coated coverslips, showed localization of β2‐adrenoceptors to the outer smooth muscle and not to the endothelium. Relaxation of mammary artery and saphenous vein to (−)‐isoprenaline is mediated via β2‐adrenoceptors located on the smooth muscle. Endothelial β2‐adrenoceptors, although present on the internal mammary artery, mediate other functions.

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Quantitative autoradiography was used to determine the location and density of beta 1- and beta 2-adrenoceptors in the right atrium (RA), left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), right atrium from an area near the atrioventricular node (RAAV) and cardiac nerves (N) taken from a patient with end-stage cardiac failure. The densities of beta-adrenoceptors detected by the non-selective beta-adrenoceptor antagonist radioligand (-)-[125I] cyanopindolol (50pM) were 4.93 (N), 10.6 (RVFW), 12.2 (RA), 12.4 (IVS), 15.8 (LVFW) and 18.7 fmol (mg protein)-1 (RAAV). The proportion of beta 2-adrenoceptors ranged from 19.5% (RAAV) to 95% (N). RA taken from patients with ischaemic heart disease had a higher density of beta-adrenoceptors (29.3 fmol (mg protein)-1). The results suggest that both beta 1- and beta 2-adrenoceptors are down-regulated in patients with end-stage cardiac failure. Positive inotropic responses were established to (-)-isoprenaline, RO363 (beta 1-selective), procaterol (beta 2-selective) and dopexamine in the absence or presence of the antagonist CGP 20712A (beta 1-selective) or ICI 118,551 (beta 2-selective) in electrically driven human right atrial appendage strips. RO363 and procaterol were nearly full agonists in this preparation and produced their responses through activation of beta 1- or beta 2-adrenoceptors, while dopexamine was a partial agonist which produced its inotropic responses through activation of both receptor subtypes. These studies demonstrate the presence and location of beta 1- and beta 2-adrenoceptors in the human heart.

Aldosterone and renin responses to head-up tilt (60 degrees for 1 h) and angiotensin II infusions (2,5 and 10 ng/kg/min) 1 h later were compared in six normal subjects during infusions of somatostatin (3 micrograms/kg/min) or saline. The infusions were performed on separate days two weeks apart. The increase in aldosterone due to exogenous angiotensin II and orthostasis were significantly attenuated by somatostatin. Neither the increase in plasma renin activity (PRA) nor the angiotensin II mediated suppression of PRA were affected by somatostatin. These findings are consistent with the recent observation that somatostatin suppresses aldosterone release in response to angiotensin II in rat adrenal cells in culture and they indicate a possible role for somatostatin in the regulation of aldosterone secretion.

Central neurogenic hyperventilation (CNH), for which there is no effective therapy, can eventually result in respiratory fatigue and death. This report describes a patient with CNH due to a brainstem anaplastic astrocytoma who also exhibited disturbances of sleep and ocular motor function. The CNH responded clinically to morphine sulfate and methadone. Analysis of ventilatory response to CO2 before and after morphine demonstrated a depression of ventilatory response (49 to 53% of baseline) and occlusion pressure response (35 to 50% of baseline) to CO2, with a requirement for high doses of naloxone (10 mg IV) to reverse the effect. Polysomnography revealed sustained hyperventilation, elevated O2 saturation, and low end-tidal CO2 throughout all stages of non-rapid eye movement (NREM) sleep, and absence of rapid eye movement (REM) sleep. Ocular motor evaluation disclosed absence of horizontal and reflexive saccades with compensatory head thrusts. Correlation of the clinical and physiologic data with the MRI abnormalities suggested that the lesion responsible for CNH in this patient might reside in the medial tegmental parapontine reticular formation. Since recurrent episodes of hyperventilation responded in a sustained fashion to IV and oral opiates, this treatment may warrant consideration in other patients with CNH.