Auditory integration training for children with autism: no behavioral benefits detected.

Auditory integration training and a control treatment were provided for 16 children with autism in a crossover experimental design. Measures, blind to treatment order, included parent and teacher ratings of behavior, direct observational recordings, IQ, language, and social/adaptive tests. Significant differences tended to show that the control condition was superior on parent-rated measures of hyperactivity and on direct observational measures of ear-occlusion. No differences were detected on teacher-rated measures. Children's IQs and language comprehension did not increase, but adaptive/social behavior scores and expressive language quotients decreased. The majority of parents (56%) were unable to report in retrospect when their child had received auditory integration training. No individual child was identified as benefiting clinically or educationally from the treatment.

A fast responding intra-arterial pH electrode for use in the peripheral artery of adult humans and large mammals: a technical development for use in research.

A rapidly responding intra-arterial pH electrode has been developed to provide a continuous record of arterial pH (pHa) in the radial artery of adult humans and large mammals. The current method for measuring pHa is discontinuous and is achieved by taking blood samples and subsequently measuring pHa in a blood gas analyser. The development of an intravascular electrode is needed for studies on the chemical control of pulmonary ventilation when a continuous record of pHa is required. It will be particularly useful in rapidly changing circumstances such as at the onset and termination of exercise and at sleep onset and arousal. The sensor of the electrode system described here consists of a pH sensitive plastic membrane adherent to the tip of a catheter. This catheter is threaded down a radial artery catheter and protrudes 2-3 mm into the arterial lumen. The electrode system has been used in patients in an intensive care unit and in patients undergoing sleep studies. No adverse complications have occurred. The records obtained showed that arterial pH faithfully followed changes in pulmonary ventilation.

Aortic pH oscillations in conscious humans and anaesthetised cats and rabbits.

Respiratory oscillations in arterial blood gas composition influence breathing in cats and dogs. Their role in the control of breathing in humans in less certain. To determine whether oscillations are very small or absent in mammals who are large or breathe fast, aortic pH oscillations, recorded with a tridodecylamine based hydrogen-ion selective electrode, were compared in humans (n = 13), cats (n = 7) and rabbits (n = 4) over a wide range of ventilation. For comparison, data were analysed in terms of the ratio of tidal volume to functional residual capacity (VT/FRC). During spontaneous breathing in rabbits, cats and humans (mean respiratory frequency fR = 61, 20.4 and and 17.5 min-1), mean VT/FRC were 1.35, 0.63 and 0.36 respectively. Corresponding pH amplitudes (pHamp) of 0.009 (0.004), 0.016 and 0.013 (0.005) pH units (mean +/- 1SD) were not significantly different. The pHamp decreased exponentially with increasing FR in each species and pHamp increased linearly with increasing VT in the 3 cats in which this was studied. The study confirms the dependence of pHamp on FR and VT and its comparability among species despite differences in body size. It also demonstrates that oscillations can be recorded in humans at FR in excess of 20 min-1.

A major binding protein for leukemia inhibitory factor in normal mouse serum: identification as a soluble form of the cellular receptor.

A protein that specifically binds leukemia inhibitory factor (LIF) has been isolated from normal mouse serum by using four successive fractionation steps: chromatography on a LIF affinity matrix, anion-exchange chromatography, size-exclusion chromatography, and preparative native gel electrophoresis. The purified LIF-binding protein (LBP) is a glycoprotein with an apparent molecular mass of 90 kDa that specifically binds 125I-labeled murine LIF with an affinity comparable to that of the low-affinity cellular LIF receptor (Kd = 600 pM). N-terminal sequencing has identified this protein as a soluble truncated form of the alpha chain of the cellular LIF receptor. LBP is present in normal mouse serum at high levels (1 microgram/ml) and these levels are elevated in pregnant mice and reduced in neonatal mice. Since normal serum concentrations of LBP can block the biological actions of LIF in culture, LBP may serve as an inhibitor of the systemic effects of locally produced LIF.

An enzyme-linked immunosorbent assay for cancer procoagulant and its potential as a new tumor marker.

Cancer procoagulant (CP) is a Mr 68,000 cysteine proteinase that initiates blood coagulation and is expressed by a variety of malignant cells but not by normally differentiated cells. Polyclonal immunoglobulin G and monoclonal immunoglobulin M antibodies were developed to purified CP and used to develop an enzyme-linked immunosorbent assay to analyze the antigen in human serum samples. The purpose of this preliminary study was to determine whether or not the analysis of CP in the serum might be a useful tumor marker. Pure CP was added to normal serum to establish a quantitative standard curve; the correlation coefficient of seven standard curves was 0.99. The upper limit of the normal range was established with 46 normal sera (mean +/- 2 SD = 0.57 microgram/ml). A total of 128 blinded serum samples were analyzed: 54 were from cancer patients (29 with gastrointestinal cancer, 22 with lung cancer, and three with urogenital cancer); 20 were from benign disease patients; and 54 were from normal individuals. All of the 13 early stage cancers were greater than 0.57 microgram/ml (positive), 31 of 41 (76%) of the late stage cancers were positive; overall, 44 of the 54 cancers (81%) were positive. Forty-nine of 54 (91%) of the normal sera and 16 of 20 (80%) of the benign disease sera were negative. Overall, the assay had a sensitivity of 81% and a specificity of 88%.

Carotid chemoreceptor response to increases in CO2 output.

The effect on carotid chemoreceptor activity of alterations in PaCO2 oscillations produced by venous CO2 loading via the small intestines was studied in anaesthetised cats, which were paralysed and ventilated at constant frequency. Changes in PaCO2 oscillations were assessed from continuously recorded oscillations of arterial pH. Chemoreceptor activity was averaged over 20-50 pH cycles to determine the amplitude (csnd ampl) and mean level (csnd mean) of the respiratory fluctuation in discharge frequency during control and CO2 loaded periods. Two groups of 5 cats were studied. In both groups, the amplitude of the PaCO2 oscillations increased by an overall average of 74.5% (standard error, SE = 9.2) with minimal change in mean PaCO2 (average increase 0.7 mm Hg), in response to an increase in VCO2 of 77.5% (SE = 7.4). When isoxia was maintained (Group 1) csnd ampl increased by 51.3% (SE = 11.1) and csnd mean by 17.3% (SE = 7.8). In Group 2, PaO2 rose by 16.7 mm Hg (SE = 1.5) during CO2 loading and both csnd ampl and csnd mean decreased by 7.4% (SE = 9.3) and 2.3% (SE = 13.3) respectively. The results demonstrate a sensitivity of chemoreceptors to changes in VCO2 which is influenced by small changes in PaO2.

Animal biotechnology.

Biotechnology has taken two directions in efforts to speed up animal production above the rates achievable by selective breeding. Recombinant DNA methods have been used to engineer protein gene products for direct administration to livestock, as in recombinant growth hormone to stimulate lactation in dairy cows or yield faster-growing, leaner carcasses in meat animals. Cloned cellulolytic genes have been inserted into ruminal microorganisms with a view to improving ruminant nutrition. The other direction is to use advanced breeding technologies to enhance performance. These include laboratory culture of large numbers of viable embryos for non-surgical transfer to surrogate mothers, development of methods for sexing sperm and embryos, cloning embryos by nuclear transplantation and gene transfer to create livestock with superior performance traits. In all cases material progress will depend upon a deeper understanding of the underlying physiological and developmental control mechanisms and public confidence that due regard is being paid to animal welfare, and to social and environmental implications.

Is hypercapnia necessary for the ventilatory response to exercise in man?

1. Continuous recordings of arterial pH, ventilation, airway CO2 and heart rate were made during rest and during 3-4 min periods of rhythmic leg exercise in four renal patients with arteriovenous shunts. 2. The patients were anaemic (haemoglobin 6.5-9.0 g/dl) but had a normal ventilatory response to exercise as judged by the ratio of the change in ventilation to the change in CO2 production. 3. Breath-by-breath oscillations in arterial pH disappeared for the majority of the exercise period in each patient. 4. Changes in mean arterial pH and end-tidal CO2 tension with exercise were inconsistent between subjects but consistent within a given subject. On average, mean arterial pH rose by 0.011 pH unit. Changes in end-tidal CO2 tension reflected changes in mean pHa by falling on average by 1 mmHg (0.13 kPa). 5. Hypercapnia and acidaemia were not found to be necessary for the ventilatory response to moderate exercise.

Derivation of CO2 output from oscillations in arterial pH.

Theory predicts that the rate of rise of the oscillation in arterial CO2 partial pressure (PaCO2) is linearly dependent on CO2 flux from venous blood to alveolar gas. We have measured, in the anesthetized cat, CO2 output (VCO2) and oscillations in arterial pH. The pH signal was differentiated to give the maximum rate of fall of pH on the downstroke of the oscillation (dpH/dt decreases max). Since oscillations in pH are due to oscillations in arterial PCO2, dpH/dt decreases max was considered to be equivalent to the maximum rate of rise of the PCO2 oscillation. VCO2 was increased by ventilating the intestines with CO2 and by the intra-arterial infusion of 2,4-dinitrophenol. VCO2 was decreased by filling the intestines with isotonic tris(hydroxymethyl)methylamine buffer. The maximum range of VCO2 covered was 7.8-51 ml/min, and the mean range was from 13.6 +/- 1.3 to 29.7 +/- 1.6 (SE) ml/min. Although CO2 loading produced a small rise and CO2 unloading a small fall in mean PaCO2, the changes were not statistically significant, so that overall the response was close to isocapnia. Over the limited range of VCO2 studied there was a highly significant linear association between dpH/dt decreases max and VCO2 which supports the contention that the slope of the upstroke of the PaCO2 oscillation is determined by the CO2 flux from mixed venous blood to alveolar gas. As such this slope is a potential chemical signal linking ventilation to CO2 production.

The effect of small changes in arterial carbon dioxide tension on carotid chemoreceptor activity in the cat.

The hypothesis that the fluctuations in carotid chemoreceptor discharge represent more than a simple proportional response to respiratory oscillations of Pa, CO2 has been examined. Simultaneous recordings of the activity in few- or multi-fibre chemoreceptor preparations of the cut carotid sinus nerve and oscillations of carotid arterial pH have been made in four anaesthetized cats which were paralysed and artificially ventilated at constant frequency. Chemoreceptor activity was averaged over a minimum of twenty consecutive pH cycles and the amplitude of the fluctuations in discharge frequency determined. Using the mean Pa, CO2 obtained from blood-gas analysis and the slope of the relationship between log Pa, CO2 and pH obtained in each cat, the amplitude of the pH oscillations was converted to Pa, CO2 amplitude. This amplitude relative to the mean Pa, CO2 has been compared with the amplitude of the corresponding fluctuation in the chemoreceptor discharge frequency recorded from the carotid sinus nerve (e.s.n.d. amplitude) relative to its mean level. Whereas the Pa, CO2 amplitude was always less than 8% of the mean Pa, CO2, the c.s.n.d. amplitude ranged from 40 to 186% of the mean discharge frequency. C.s.n.d. amplitude was divided by the corresponding Pa, CO2 amplitude to give an index of the sensitivity of the chemoreceptors to Pa, CO2. This sensitivity has been compared with that determined from the mean discharge frequency produced in response to changes in mean Pa, CO2 comparable in magnitude to the Pa, CO2 amplitude. The former sensitivity was usually at least 3 times greater than the latter. Examination of the fluctuations in chemoreceptor discharge frequency in relation to the corresponding pH oscillations revealed that whereas the minimum discharge frequency coincided with the alkaline peak of the pH oscillation (trough of the Pa, CO2 oscillation), the maximum discharge frequency did not invariably coincide with the acid trough of the pH oscillation (peak of the Pa, CO2 oscillation). On 30% of occasions, the maximum discharge frequency was associated with the region of maximum rate of fall of pH (maximum rate of rise of Pa, CO2). It was concluded that fluctuations in the discharge of carotid chemoreceptors cannot be accounted for on the basis of a simple proportional relationship to Pa, CO2. They contain a large rate of change component.

Cysteine proteinase procoagulant from amnion-chorion.

Various coagulation abnormalities are associated with pregnancy. Several investigators have suggested that there may be a unique procoagulant associated with amniotic tissue and fluid. We identified a cysteine proteinase from malignant tissue, cancer procoagulant, and had reason to believe a similar proteinase may be present in amniotic tissue. Amniotic fluid and extracts of amnion-chorion were purified by immunoaffinity chromatography with an antibody that was developed to cancer procoagulant antigen. The purified amnion-chorion procoagulant initiated clotting in normal and factor VII-deficient citrated human plasma and directly activated pure human factor X in a two-stage clotting assay. It was inhibited by 1 mmol/L of iodoacetamide and 0.1 mmol/L of HgCl2, and the procoagulant activity was activated by 10 mmol/L of KCN; these are classic properties of cysteine proteinases. The pure amnion-chorion procoagulant had the same mol wt and immunologic determinants as cancer procoagulant from rabbit V2 carcinoma, as determined by crossed immunodiffusion, suggesting that the same or very similar proteins were associated with both tissues. Thus, this procoagulant may be derived from both undifferentiated and dedifferentiated cells.

The role of spinal cord transmission in the ventilatory response to electrically induced exercise in the anaesthetized dog.

1. The ventilatory response to electrically induced ;exercise' was studied in six chloralose-anaesthetized dogs. The on-transient and steady-state responses to ;exercise' were compared in the same dogs before and after spinal cord transection at T8/9 (dermatome level T6/7) on fifteen occasions.2. Phasic hind limb ;exercise' was induced for periods of 4 min by passing current (2 Hz modulated 50 Hz sine wave) between two needles inserted through the hamstring muscles. The maximum current used was 30 mA. This was below the level previously found to produce an artifactual stimulation of breathing with the cord intact.3. Cord transection produced no significant change in either the resting values of ventilation ( V(I)) and CO(2) production ( V(CO) (2)) or the ventilatory equivalent for CO(2) during ;exercise' ( big up tri, open V(I)/ big up tri, open V(CO) (2)).4. During the steady state of exercise P(a, CO) (2) was on average significantly lower than at rest with the cord intact (mean big up tri, openP(a, CO) (2), - 2.1 mmHg; range - 5.7 to + 1), and higher, though not significantly, with the cord cut (mean P(a, CO) (2), + 1.2 mmHg; range - 1.5 to + 4.3). However, even in the absence of spinal cord transmission, the ventilatory response to exercise could not be accounted for on the basis of CO(2) sensitivity; the big up tri, open V(I)/ big up tri, openP(a,CO) (2) obtained with exercise (apparent sensitivity) was significantly greater than that obtained with CO(2) inhalation (true sensitivity) both before and after cord section.5. V(I) and V(CO) (2) increased more slowly with the cord cut than with the cord intact. This was thought to be due to a slower increase in venous return in the absence of sympathetic innervation of the lower half of the body following cord transection.6. Similar experiments were performed during muscle paralysis (following gallamine triethiodide). Ventilation was maintained with a respirator controlled by phrenic nerve activity. These experiments showed an increase in ventilation, independent of muscle contraction, which was only present when the cord was intact and which was confined to the on-transient. Only in the absence of spinal cord transmission could there be certainty that the dynamics of the ventilatory response to electrically induced ;exercise' was free of artifact.7. It was concluded that spinal cord transmission is not necessary for the steady-state ventilatory response to electrically induced exercise of the hind limbs.8. The dog with spinal cord transection provides a suitable model for the study of the chemical control of breathing during electrically induced exercise.

The ph oscillations in arterial blood during exercise; a potential signal for the ventilatory response in the dog.

1. The effect of electrically induced ;exercise' on the respiratory oscillation of arterial pH was studied in chloralose-anaesthetized dogs with spinal cord transection at T8/9 (dermatome level T6/7).2. Respiratory oscillations of arterial pH (presumed to be due to oscillations of arterial P(CO2)) were sensed with a fast-responding electrode in one carotid artery. Breath-by-breath estimates of the maximum rate of change of pH of the downstroke of the pH oscillation (dpH/dt downward arrowmax) were obtained by differentiating the pH signal.3. Consistent with the findings of the previous paper (Cross et al. 1982), the ventilatory response to exercise could not be explained on the basis of sensitivity to CO(2); the Delta V(I)/DeltaP(a, CO2) was significantly greater for ;exercise' than for CO(2) inhalation.4. On average, the amplitude of the pH oscillations decreased during ;exercise'. The change in the phase relationship (varphi) between respiratory and pH cycles, although significant from the second breath onwards, was not thought to be responsible for the increased ventilation V(I); the direction of the change was opposite to that previously found to increase V(I).5. Inspiratory duration (t(i)), expiratory duration (t(e)), V(I) and the dpH/dt downward arrowmax changed significantly by the third breath of ;exercise'. A significantly linear relationship was obtained between t(e) and dpH/dt downward arrowmax during the on-transient (first ten breaths) of ;exercise'. This relationship was maintained throughout ;exercise'. V(I) and dpH/dt downward arrowmax were also linearly related during the on-transient, although the same relationship did not hold true throughout ;exercise'.6. The dpH/dt downward arrowmax was related to CO(2) production ( V(CO2)) lending support to the prediction that the slope of the downstroke of the pH oscillation is a function of V(CO2).7. It was concluded that the dpH/dt downward arrowmax (dpCO(2)/dt upward arrowmax) is a potential humoral signal in ;exercise' and could account totally for the shortening of t(e). Since there was a late rise in V(I) (due to an increase in tidal volume V(T)) in the absence of a change in dpH/dt downward arrowmax, it was considered unlikely that the dpH/dt downward arrowmax was the only humoral signal present during ;exercise'.

Interactions between lung stretch and PaCO2 in modulating ventilatory activity in dogs.

The effects of changes in airway pressure (Paw) and arterial PCO2 (PaCO2) on ventilatory activity were studied in anesthetized thoracotomized dogs in which both lungs were ventilated separately. Pulmonary artery occlusion on one side and contralateral vagotomy allowed the reflex effects on ventilation of changes in Paw and PaCO2 to be elicited independently of each other. Ventilatory activity was assessed from integrated efferent phrenic activity, analyzed with respect to burst amplitude (Phr), burst frequency (f), and inspiratory TI) and expiratory duration (TE). While Phr increased linearly with PaCO2, it was independent of Paw. Both PaCO2 and Paw affected f in a complex nonadditive way; this response was entirely mediated by effects on TE, TI being unaffected by either stimulus. The analog of ventilation, estimated as Phr x f, increased linearly with PaCO2 and decreased linearly with Paw, but the effects of both stimuli appeared to be additive. It is concluded that the apparently simple effect of Paw and PaCO2 on ventilation results from more complex effects these stimuli exert on its components.

The summation of left and right lung volume information in the control of breathing in dogs.

1. Reflex respiratory responses to unilateral and bilateral changes of lung volume have been studied in anaesthetized paralysed, open-chest dogs.2. The two lungs were separately ventilated by two phrenic-driven respirators via a specially designed double-lumen tube. Respiratory motor output was measured from the phrenic motoneurone activity recorded from the C(5) root. Expiratory lung volumes were set by the use of expiratory threshold loads (e.t.l.s).3. The reflex changes of expiratory time (t(e)) were used to study the summation of left and right expiratory lung volume information. Changes in the peak amplitude of the phrenic ;integral' (Phr) and inspiratory time (t(i)) were used to assess summation of left and right tidal volume information.4. Summation in the reflex responses to bilateral lung volume changes was estimated by comparing the measured responses to these manoeuvres with the sum of the component unilaterally evoked responses. If simple addition were present, response (measured)/response (predicted) would equal 1.0 Mutual facilitation would give a value higher than this; mutual inhibition, a lower value.5. The responses of t(e) to changes of e.t.l. on the right side were always greater than for changes confined to the left, and in each animal the response of t(e) to bilateral changes of e.t.l. were greater than for either of the unilaterally evoked responses. In six out of eight animals this was shown to be due to simple addition of the responses evoked from the two lungs individually. In the remaining two animals, slight mutual inhibition was seen.6. The tidal volume V(T) was changed in one or both lungs. During the bilateral V(T) changes, the volumes were changed simultaneously, either in the same direction (;same' V(T) changes) or in one direction in one lung and in the opposite direction in the other (;opposite' V(T) changes).7. In the bilateral ;same' V(T) changes, mutual facilitation was seen in the response of Phr; Phr (measured)/Phr (predicted) = 1.60 +/- 0.42 (s.d.), n = 8. There was only slight facilitation in the response of t(i); t(i) (measured)/t(i) (predicted) = 1.18 +/- 0.17, n = 8.8. With the bilateral ;opposite' V(T) changes, responses of t(i) and Phr were markedly and significantly reduced compared to those for the bilateral ;same' V(T) changes. During these manoeuvres significant mutual inhibition was seen in the response of t(i), and the predicted responses of Phr in general could not be correlated with the measured response.9. The responses of the phrenic ;integrals' were the same in both right and left phrenic nerves.10. Unilateral vagotomy abolished both the responses of Phr and t(i) to ipsilateral V(T) changes in the range +/- 100% of control V(T), and also the response of t(e) to ipsilateral expiratory volume changes.

Ventilatory response to inhaled and infused CO2: relationship to the oscillating signal.

The purpose of this study was to determine the relationship between the respiratory oscillations of CO2 and the ventilatory response to CO2. Cats anaesthetized with chloralose and urethane were given CO2 either by exchange transfusion into the inferior vena cava or by inhalation. Changes of amplitude of the respiratory oscillations of CO2 (amp PCO2) were assessed from measurements of the amplitude of the arterial pH oscillations (amp pH). For short periods of CO2 loading (2-8 min), the ventilatory response to CO2 was greater for venous than for airway loading; this difference was statistically significant at low and intermediate loads but not at high loads. The dependence of the respiratory response to the route of administration of CO2 could not be related to amp PCO2. For long periods of CO2 loading (20 min or more) there was no marked change of minute ventilation when the route of administration was changed from airway to venous route, despite an increase of amp pH at both low and intermediate loads. We suggest that the dependence of ventilatory response to CO2 on the route of administration observed in this study was mainly due to a longer period required to attain steady state conditions for CO2 inhalation, and that the respiratory oscillations of CO2 do not affect the ventilatory response to CO2.

A factor X-activating cysteine protease from malignant tissue.

A proteolytic procoagulant has been identified in extracts of human and animal tumors and in cultured malignant cells. It directly activated Factor X but its similarity to other Factor S-activating serine proteases was not clear. This study describes work done to determine whether this enzyme, cancer procoagulant, is a serine or cysteine protease. Purified cancer procoagulant from rabbit V2 carcinoma was bound to a p-chloromercurialbenzoate-agarose affinity column and was eluted with dithiothreitol. The initiation of recalcified, citrated plasma coagulation activity by cancer procoagulant was inhibited by 5 mM diisopropylfluorophosphate, 1 mM phenylmethylsulfonylfluoride, 0.1 mM HgCl2, and 1 mM iodoacetamide. Activity was restored in the diisopropylfluorophosphate-, phenylmethylsulfonylfluoride-, and HgCl2-inhibited samples by 5 mM dithiothreitol; iodoacetamide inhibition was irreversible. Russell's viper venom, a control Factor X-activating serine protease, was not inhibited by either 0.1 mM HgCl2 or 1 mM iodoacetamide. The direct activation of Factor X by cancer procoagulant in a two-stage assay was inhibited by diisopropylfluorophosphate and iodoacetamide. Diisopropylfluorophosphate inhibits serine proteases, and an undefined impurity in most commercial preparations inhibits cysteine proteases. Hydrolysis of diisopropylfluorophosphate with CuSO4 and imidazole virtually eliminated inhibition of thrombin, but cancer procoagulant inhibition remained complete, suggesting that cancer procoagulant was inhibited by the undefined impurity. These results suggest that cancer procoagulant is a cysteine endopeptidase, which distinguishes it from other coagulation factors including tissue factor. This and other data suggest that neoplastic cells produce this unique cysteine protease which may initiate blood coagulation.

Currents and portents in biomedical research.

The present progress and prospects of biomedical research are discussed by reference to the syndrome of "restrictive utilitarianism" which governs much of the public and official attitude to research. The signs and symptoms of the condition are described and some of the prophylactic and therapeutic measures that should be taken to offset the threat it poses to the future welfare of man and animals are suggested.

Effect of the suckling stimulus on secretion of prolactin and luteinizing hormone in conscious and anaesthetized rats.

Luteinizing hormone and prolactin were measured in plasma samples taken from conscious and anaesthetized, lactating, suckled rats after overnight separation from their litters except for one pup. In the conscious rats, there was a marked fall in plasma LH concentration (P < 0.05), and a large increase in that of prolactin (P < 0.01) within 30 min of returning the pups to the mothers. When the mothers were anaesthetized with urethane and then suckled by their litters, there was no significant change in plasma LH values, but prolactin values rose significantly (P < 0.05) after 2.5 h of suckling. However, suckling caused no significant change in plasma concentrations of LH or prolactin when the milk-ejection frequency was doubled (P < 0.001) by administering xylazine to urethane-anaesthetized mothers. It was concluded that the conscious lactating rat, separated from her litter overnight, is a very sensitive model for studying the neural events controlling LH and prolactin secretion during suckling. Anaesthesia by urethane blocks this sensitized response, but the blockade is not associated with interference in the milk-ejection reflex.