10-fold Increment Research Articles

THE RELATIONSHIP BETWEEN SERIAL MEASUREMENTS OF THE LEVEL OF A BLADDER TUMOR ASSOCIATED ANTIGEN AND THE POTENTIAL FOR RECURRENCE

We evaluate the relationship between a serially assessed quantitative diagnostic marker (QDM) and the hazard function for the diagnosis of recurrence of bladder cancer. The marker is based on a bladder tumor associated antigen (BTA TRAK) assay. We present a rigorous approach to the evaluation of diagnostic markers to be used for recurrence monitoring. Archival voided urine samples serially collected from 187 patients with a prior diagnosis of transitional cell carcinoma of the bladder were measured for BTA TRAK, an assay performed in clinical laboratories. All patients had been treated for stage Ta or T1 transitional cell carcinoma and were undergoing periodic assessments for recurrence. The results from the QDM were not used in case management. Time to histologically confirmed recurrence of transitional cell carcinoma was modeled using proportional hazard regression with the serial measurements of QDM levels and other variables as covariates. QDM levels are in the model as a time dependent covariate on the base 10 logarithmic scale. The estimated hazard ratio for QDM level indicated a 60% increase in the hazard for the diagnosis of recurrence for each 10-fold increment in the marker level (p = 0.013). A statistically significant relationship between the serially assessed QDM levels and the hazard for the diagnosis of recurrence has been established but the definition of optimum strategies for use of this relationship in clinical practice will require further study. Meanwhile, a prudent action based on the statistical relationship would be to shorten surveillance intervals for patients with high QDM levels.

Effect of long-term treatment with aromatase inhibitor on testicular function of adult male bonnet monkeys ( M. radiata)

The role/need for estrogen in regulating testicular function of adult male bonnet monkeys ( M. radiata) has been investigated by dosing orally a group of five normal males 2.5 mgs of CGP 47645, a long-acting nonsteroidal aromatase inhibitor (AI), once every 5 days for over 150 days. Such treatment resulted in a 10-fold increment in nocturnal serum testosterone (T) levels, which were sustained for 85 days of treatment, and a twofold increment in basal serum T levels was present throughout the 150 days of treatment. Analysis of ejaculated semen showed a marked reduction (∼90%) in sperm counts in four out of five monkeys between Days 55–85 of treatment. During this period, the motility score also was markedly reduced from a normal score of 3-5 to 0-2. Flow cytometric analysis of testicular germ cells obtained from biopsy tissue taken on Days 63 and 120 indicated a marked reduction only in elongating/elongated spermatid population (compared to Day 0 values), suggesting inhibition in spermiogenic process. Epididymal sperm maturation also seemed effected as sperm chromatin, on flow cytometric analysis for decondensability following exposure to 5 mM dithiotreitol, showed to be in a hypercondensed state. This study thus indicates that estrogen has an important role in providing normal testicular and sperm function in the primate.

Cardiovascular effects of plant secondary metabolites norarmepavine, coclaurine and norcoclaurine

The cardiovascular effects of (±)-norarmepavine, a benzylisoquinoline alkaloid of natural origin, have been determined on anaesthetized rats in vivo, on spontaneously beating atria and on aortic smooth muscle. In aorta, the effects of (±)-coclaurine and (±)-norcoclaurine, benzylisoquinolines with a related structure, were also compared. (±)-Norarmepavine (10 mg/kg i.v.) decreased the mean arterial pressure and heart rate by 45% and 21%, respectively. (±)-Norarmepavine (10−5–10−3 M) showed a negative chronotropic effect on rat-isolated atria, decreasing the spontaneous frequency by about 54%. Aortic rings contracted with KCl 70 mM were relaxed in a concentration-dependent manner by (±)-norarmepavine, (±)-coclaurine and (±)-norcoclaurine (10−6–10−3 M). The two earlier alkaloids exhibited an efficacy similar to verapamil, relaxing the aortic rings by 100%. (±)-Norcoclaurine exhibited a lower efficacy. These results point to the importance of methylation of these compounds. The rank order of potency was: (±)-verapamil > (±)-norarmepavine > (±)-norcoclaurine > (±)-coclaurine. The alkaloids shifted to the right the calcium-dependent contraction curves, denoting a calcium antagonist-like effect; however, only a 10-fold increment of (±)-norcoclaurine concentration produced an equivalent effect. Our results demonstrate the hypotensive and bradycardic properties of (±)-norarmepavine. It is proposed that this alkaloid could somehow modulate calcium entry, its intracellular release or the calcium sensitivity of the cell contractile-machinery, previously postulated for coclaurine. (±)-Norcoclaurine effects reported here are not in agreement with the proposal of (±)-norcoclaurine as a calcium channel activator or β1-adrenoceptor agonist. © 1998 John Wiley & Sons, Ltd.

Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel.

Synaptotagmins are synaptic vesicle proteins containing two calcium-binding C2 domains which are involved in coupling calcium influx through voltage-gated channels to vesicle fusion and exocytosis of neurotransmitters. The interaction of synaptotagmins with native P/Q-type calcium channels was studied in solubilized synaptosomes from rat cerebellum. Antibodies against synaptotagmins I and II, but not IV co-immunoprecipitated [125I]omega-conotoxin MVIIC-labelled calcium channels. Direct interactions were studied between in vitro-translated [35S]synaptotagmin I and fusion proteins containing cytoplasmic loops of the alpha1A subunit (BI isoform). Gel overlay revealed the association of synaptotagmin I with a single region (residues 780-969) located in the intracellular loop connecting homologous domains II and III. Saturable calcium-independent binding occurred with equilibrium dissociation constants of 70 nM and 340 nM at 4 degrees C and pH 7.4, and association was blocked by addition of excess recombinant synaptotagmin I. Direct synaptotagmin binding to the pore-forming subunit of the P/Q-type channel may optimally locate the calcium-binding sites that initiate exocytosis within a zone of voltage-gated calcium entry.

The number of Bradyrhizobium SP. ( Lupinus) applied to seed and its effect on rhizosphere colonization, nodulation and yield of lupin

In field experiments we investigated the roles of inoculum potential of Bradyrhizobium sp. ( Lupinus) and quantity of peat used to inoculate seed on the nodulation and yield of lupins. Within the range 0.125–3 times the Australian recommended rate of peat application (2.5 g peat kg −1 lupin seed), the amount of peat had no effect on nodulation or grain yield. In the first experiment, seven inoculum potentials were applied within the range log 10 0.32–6.28 bradyrhizobia per seed in 7, 10-fold increments which spanned the recommended rate of login 5.55 per seed. Inoculum potentials of log 10 6.27 and 5.27 improved the colonization of lupin rhizospheres and increased early nodulation, nodule number and nodule mass. Nodule mass was increased from 65 to 393 mg plant −1 at 43 days by increasing the inoculum from log 10 4.27 to 6.27 bradyrhizobia seed −1. Grain yield and % N in the grain were not significantly different ( P > 0.05) between potentials of logio 4.27 and 6.27. In the second experiment, higher potentials of 6.80 and 7.28 further improved rhizosphere colonization and increased nodule mass. Studies of the survival of the inoculum, during inoculation, sowing and in the soil, identified a large mortality factor; 95% of bacteria died between inoculation and sowing and of those surviving, 83% died after 22.5 h in the soil. These observations have important implications for setting new standards for commercial inoculants and for emphasizing the care needed in handling inoculated seed to reduce the death of bradyrhizobia in the period between inoculation and sowing.

Lanierone: A new pheromone component fromIps pini (Coleoptera: Scolytidae) in New York

A new pheromone component, lanierone, (2-hydroxy-4,4,6-trimethyl-2,5-cyclohexadien-1-one) was isolated and identified from a Porapak Q collection of volatiles from maleIps pini from New York through GC fractionation, bioassay, and spectrometry. In both the laboratory and the field, synthetic lanierone, in a 1:100 ratio with synthetic ipsdienol, is as attractive as natural pheromone sources. Synthetic ipsdienol alone is not attractive in the laboratory and only weakly attractive in the field. Varying the ratio of lanierone to ipsdienol in the field from 10(-4)∶1 to 1∶1 in 10-fold increments resulted in an increased number of beetles trapped at the three lower ratios, but also in an increase in the proportion of males trapped. In the field, all combinations of lanierone to ipsdienol attracted proportionately fewer males than did pheromone-producing male beetles. GC and GC-MS analyses of Porapak Q-trapped volatiles revealed that lanierone is produced in an amount equal to about 0.2% of that of ipsdienol and is produced exclusively by males. The small amount of lanierone produced, together with a GC retention time similar to that of ipsdienol on a nonpolar column, probably confounded its detection in earlier studies.

Inhibition of Mediator Release in Allergic Rhinitis by Pretreatment with Topical Glucocorticosteroids

Patients with allergic rhinitis often have immediate symptoms after antigen challenge (the early-phase response), followed several hours later by a recurrence of symptoms (the late-phase response). Systemic glucocorticosteroids are known to inhibit the late-phase but not the early-phase response. We studied the effect of one week of pretreatment with topical (rather than systemic) glucocorticosteroids on the response to nasal challenge with antigen in a double-blind, randomized, placebo-controlled crossover study of 13 allergic patients who had previously had a dual response to nasal challenge. The patients were challenged with three 10-fold increments of allergen, producing an early response, and were then followed for 11 hours, encompassing the late response, before they were rechallenged with the lowest dose of allergen. We monitored their responses by means of symptom scores and measurements of the levels of histamine, tosyl-L-arginine methyl ester (TAME)-esterase activity, and kinins in nasal lavages. Topical glucocorticosteroids significantly reduced both the symptoms and the levels of histamine, TAME-esterase activity, and kinins in the early, late, and rechallenge allergic reactions. The fact that, in contrast to treatment with systemic glucocorticosteroids, prolonged pretreatment with topical glucocorticosteroids inhibited the early-phase response to antigen suggests that the route and duration of administration affect the mechanisms of action of the steroids. We conclude that inhibition of the early-phase as well as the late-phase response by topical glucocorticosteroids may provide an advantage over treatment with systemic glucocorticosteroids in patients with allergic rhinitis.

Effect of sucralfate on the viscosity of gastric mucus and the permeability to hydrogen ion.

The effect of sucralfate on the viscosity of pig gastric mucus and on its ability to retard the diffusion of hydrogen ion was investigated. Using a cone/plate viscometer at shear rates between 1.15 and 230 s-1, it was found that preincubation of mucus with increasing concentrations of sucralfate led to a gradual enhancement of the mucus viscosity. This enhancement in viscosity was proportional to the sucralfate concentration up to 1.0 X 10(-4) M and increased about 18% for each 10-fold increment in its concentration. The permeability measurements, conducted in a specially designed two compartment chamber, revealed that addition of sucralfate to gastric mucus had a profound beneficiary effect on its ability to retard the diffusion of hydrogen ion. In the presence of 1.0 X 10(-6) M sucralfate the permeability of mucus to hydrogen ion decreased by 35%, while the 1.0 X 10(-3) M sucralfate reduced the mucus permeability by 68%. The results show that sucralfate increases the viscosity of gastric mucus and improves its ability to impede the hydrogen ion penetration.

Interaction of low density lipoproteins with arterial proteoglycans The role of charge and sialic acid content

The interaction of low density lipoproteins (LDL) with chondroitin sulfate-rich arterial proteoglycans appears to be initiated by coulombic interactions that lead to insoluble complexes. Once formed, large LDL aggregates are held together by non-polar associations. The irreversible formation of LDL proteoglycans aggregates was evaluated for different LDL preparations by definition of an avidity coefficient (A r) using a Langmuir isotherm. LDL from different subjects, when tested against the same lipoprotein-complexing proteoglycan (LCP), gave A r values ranging from 1−9 × 10 6 L M . High avidity values were associated to lipoproteins with apparent isoelectric points above 6.5. These lipoproteins show low Sialic acids content. The content of N-acetyl and N-acetyl,O-acetyl Sialic acid was found inversely correlated with the avidity coefficient for the arterial LCP. Reductions of 42% on the LDL sialic acid content, by neuraminidase treatment, induced a 10-fold increment in their avidity for the lipoprotein complexing proteoglycan. The results indicate that at low ionic strength and physiological Ca 2+-concentration and pH, the surface charge of LDL is an important modulator of the interaction with the arterial proteoglycan. Sialic acid, perhaps because of its exposure at the LDL surface, plays a determinant role in the in vitro association of LDL with the polyanionic proteoglycans. It is possible that in the intima-media the sialic residues of LDL and its balance of surface charges will control part of the interactions with the proteoglycans of the extracellular matrix.

Effects of pH, calcium, and succinate on sodium citrate cotransport in renal microvilli.

Sodium-dependent citrate uptake (v) by rabbit renal brush border vesicles was studied as a function of pH and Ca2+, citrate, and succinate concentrations to evaluate the hypothesis that factors which alter renal citrate reabsorption also alter v. At pH 8 a 10-fold increment in citrate concentration (up to 3.3 mM) was required to achieve the same v observed at pH 7. This provides proof that the protonated citrates are the effective substrates for v. At higher citrate concentrations (5-10 mM) and pH 8, substrate inhibition of v occurred. Studies of the substrate concentration dependency of v at various pH levels and calcium concentrations indicated that v was competitively inhibited by citrate3-. Changes in calcium concentrations altered v by altering the protonated citrate and citrate3- concentrations; v showed countertransport with succinate. Sodium-dependent succinate uptake (vs) was not pH dependent but was more inhibited by 1 mM citrate at pH 7 than at pH 8, indicating that the protonated citrates are inhibitors of vs. However, citrate3- was also found to inhibit vs. Thus, changes in v at the brush border membrane due to the effects of pH or calcium concentration on the protonated citrate concentration and to competition between polycarboxylates may be relevant to changes in renal citrate reabsorption in vivo.

Allergy to semisynthetic penicillins in cystic fibrosis

Allergic reactions to anti-Pseudomonal penicillin derivatives are an increasing problem in therapy of cystic fibrosis lung disease. We evaluated 15 patients, ages 12 to 37 years, with documented allergic reactions to carbenicillin, ticarcillin, or piperacillin. Intradermal skin test reactions were positive for benzylpenicillin in seven patients, penicilloyl-polylysine in one, and ticarcillin or piperacillin in eight, for a total of 11 of 11 tested. Results of radioallergosorbent testing to penicilloyl conjugates were positive in eight of 14 patients and equivocal in four others. Overall, skin tests or RAST results were positive in 13 of 15 patients. All patients were desensitized with a semisynthetic penicillin by continuous serial intravenous infusion of 10-fold dose increments, beginning with 10(-6) of the therapeutic dose. Desensitization was successful in 25 of 26 instances. After intravenously administered therapy, maintenance of desensitization with dicloxacillin orally was unsuccessful in four of six patients. We conclude that (1) allergy to semisynthetic penicillins in cystic fibrosis usually is IgE mediated; (2) such allergy can be evaluated by skin testing; (3) it can be safely and in most cases successfully treated by intravenous desensitization; and (4) allergic patients should be desensitized on each subsequent admission for intravenously administered therapy.

Arterial-venous nitroglycerin gradient during intravenous infusion in man.

We assessed the concentration of nitroglycerin (GTN) measured in plasma at different sampling sites in the circulation during a constant i.v. infusion. Twenty patients with chronic congestive cardiac failure underwent hemodynamic monitoring during i.v. GTN infusion. Our end point was a reduction in pulmonary capillary wedge pressure by at least 25% of its control value or a 10-fold increment over the initial infusion rate. Nitroglycerin infusion produced no change in heart rate, a reduction in mean arterial pressure from 90 +/- 21 (+/- SD) to 83 +/- 17 mm Hg (p less than 0.001), a fall in total peripheral resistance from 24.3 +/- 10.8 to 20.8 +/- 7.0 units (p less than 0.02), and a substantial reduction in both pulmonary capillary wedge pressure (from 27 +/- 6 to 20 +/- 6 mm Hg, p less than 0.001) and right atrial pressure (from 12 +/- 4 to 8 +/- 4 mm Hg, p less than 0.001). The concentrations of GTN in the pulmonary artery and systemic artery were similar (29.8 ng/ml +/- 52.8 and 25.1 +/- 48.4 ng/ml, respectively) and considerably higher than the concentration in the peripheral vein (7.3 +/- 15.4 ng/ml). There was a 17.4 +/- 19.1% extraction of GTN across the pulmonary vascular bed and a 60.8 +/- 27.2% extraction across the arterial-venous bed (p less than 0.001). There was no relationship between the arterial-venous extraction and the magnitude of arterial plasma (GTN concentration, the duration of the infusion of GTN or the total dose administered. These data show that a better understanding of GTN pharmacokinetics is provided by simultaneous arterial and venous samples.

Long-term ticarcillin desensitization by the continuous oral administration of penicillin

Patients with documented allergies to penicillin may require desensitization for treatment of severe infections, and maintenance of desensitization by continuous oral administration of the drug has been proposed. We report the case of an 11-yr-old boy with cystic fibrosis who was allergic to ticarcillin and responded to desensitization and to subsequent maintenance with oral penicillin. After an intravenous dose of ticarcillin for pseudomonas pneumonia, he devloped throat burning, periorbital edema, and pruritus, which responded to antihistamines and epinephrine. Penicillin skin testing was positive with intradermal injections of benzylpenicilloyl polylysine (36 mm 2 wheal) and 1:10,000 dilutions of 3.3 mg/ml stock solutions of minor determinant mixture (25 mm 2 wheal) and ticarcillin (25 mm 2 wheal). Intravenous desensitization to ticarcillin was performed according to a schedule similar to that for penicillin, beginning with 1:1,000,000 dilution of the proposed therapeutic dose of ticarcillin and advancing by 10-fold increments. Nasal pruritus, periorbital edema, and urticaria developed with 1:10 and full-strength dilutions but responded to antihistamine. The patient tolerated a full therapeutic-course, with occasional symptoms. To prevent need for further desensitization, the patient was begun on continuous oral penicillin (250 mg) every 12 hr. Repeat skin tests 6 wk later were negative but converted to positive (25 mm 2 wheal with undiluted ticarcillin) when the penicillin dose was decreased to 250 mg every 24 hr and prompted repeat desensitization for an infection occurring at this time. A change in oral penicillin therapy to every 8 hr ablated skin-test reactivity and allowed the use of ticarcillin without prior desensitization, with only mild nasal itching and congestion. Increasing the serum concentration of ticarcillin with the use of the renal tubular blocking agent, probenecid, produced a transient return of allergic symptoms, suggesting that the patient was only partially desensitized. This case demonstrates the successful application of penicillin desensitization procedures to a semisynthetic penicillin and maintenance of desensitization by continuous oral therapy with the parent drug.

Influence of variations in the chemical structure of heparin on its anticoagulant and anti-factor Xa activities

Fractions of hog mucosal heparin, distinguished by large differences in chemical composition, were found to vary widely in anticoagulant activity and in their ability to potentiate the inhibition of Factor Xa. Anticoagulant activity was highest for fractions that consisted mainly of L -iduronic acid 2-sulfate and 2-deoxy-2-sulfamino- D -glucose 6-sulfate, and decreased overall by a factor of 3 (from 145 to 56 USP units) as the proportion of residues of 2-acetamido-2-deoxy- D -glucose, D -glucuronic acid and L -iduronic acid became progressively more prominent. Conversely, a 10-fold increment in anti-Xa activity (from 59 to 639 units/mg) accompanied increases in the proportions of the minor, non-sulfated, heparin constituents. These findings suggest that individual steps of the coagulation process are subject to selective catalytic effects on reaction rate by differently constituted molecules within a heparin preparation.

Effects of illumination level on the rat's rhythmicity of brain self-stimulation behavior

Rhythmic patterns in the rat's brain self-stimulation behavior were analyzed across levels of illumination, including conditions of constant illumination (LL), constant darkness (DD), and light-dark cycles (LD 12 : 12). LD entrainment was achieved with light intensities ranging from 0.25 to 440 lux, and little or no change was found in the phase-angle difference between the dominant spectral peak and the light transitions. Under constant conditions, the circadian period (τ) increased in proportion to illumination level, with means ranging from 24.10 h (DD) to 25.90 h (LL 440 lux). τ increased linearly as a function of log I within the range of 0.25 to 30 lux, yielding a change of 0.28 h for a 10-fold increment in illumination level, a value which closely matches Aschoff's [3] preliminary estimate of Δτ/ΔILL for the rat. The circadian spectral component was influenced by several factors. (1) Re-entrainment protocol. Given a succession of LL conditions without entrainment segments in between, circadian rhythmicity was obscured at high illumination levels. (2) Duration of LL exposure. Even following an entrainment segment, long-term LL resulted in reduced power or loss of the circadian component. (3) LD vs LL. Spectral power was consistently higher under entrainment than under corresponding LL intensities, and there was a trend toward reduced power as a function of LL intensity. A wide range of ultradian spectral components was found across conditions. Under entrainment, most such components were harmonics of the circadian a circadian process, although the functional significance of ultradian-circadian interactions has yet to be ascertained (cf. refs 15, 17 and 21). It is posible that ultradian cyclicities which underly the temporal stream of behavior come to dominate the spectrum under free-running conditions either as decoupled elements of the circadian system or as independent elements which are otherwise masked by the circadian cycle. Regardless of mechanism, their presence in the spectral distribution describes the changes in temporal organization when unified daily rhythmicity loses its internal synchrony.

Effects of illumination level on the rat's rhythmicity of brain self-stimulation behavior

Rhythmic patterns in the rat's brain self-stimulation behavior were analyzed across levels of illumination, including conditions of constant illumination (LL), constant darkness (DD), and light-dark cycles (LD 12 : 12). LD entrainment was achieved with light intensities ranging from 0.25 to 440 lux, and little or no change was found in the phase-angle difference between the dominant spectral peak and the light transitions. Under constant conditions, the circadian period (τ) increased in proportion to illumination level, with means ranging from 24.10 h (DD) to 25.90 h (LL 440 lux). τ increased linearly as a function of log I within the range of 0.25 to 30 lux, yielding a change of 0.28 h for a 10-fold increment in illumination level, a value which closely matches Aschoff's [3] preliminary estimate of Δτ/ΔILL for the rat. The circadian spectral component was influenced by several factors. (1) Re-entrainment protocol. Given a succession of LL conditions without entrainment segments in between, circadian rhythmicity was obscured at high illumination levels. (2) Duration of LL exposure. Even following an entrainment segment, long-term LL resulted in reduced power or loss of the circadian component. (3) LD vs LL. Spectral power was consistently higher under entrainment than under corresponding LL intensities, and there was a trend toward reduced power as a function of LL intensity. A wide range of ultradian spectral components was found across conditions. Under entrainment, most such components were harmonics of the circadian a circadian process, although the functional significance of ultradian-circadian interactions has yet to be ascertained (cf. refs 15, 17 and 21). It is posible that ultradian cyclicities which underly the temporal stream of behavior come to dominate the spectrum under free-running conditions either as decoupled elements of the circadian system or as independent elements which are otherwise masked by the circadian cycle. Regardless of mechanism, their presence in the spectral distribution describes the changes in temporal organization when unified daily rhythmicity loses its internal synchrony.

Semi-quantitative urine culture. A comparative study of four methods

Personnel working in a routine clinical microbiology laboratory performed a double blind experiment in which they cultured simulated urines (bacterial suspensions) using the following semi-quantitative methods: standard loop, 1 mm in internal diameter, streaked in a simple snake track; Orion agar dipslide; Urostrip filter paper transfer; and Microstix culture strip. The bacteria used were Escherichia coli and Streptococcus faeculis . The test suspensions ranged from y × 10 3 organisms/ml to y × 10 7 organisms/ml in 10-fold increments. The viable counts were assessed by the standard pour plate technique and y was 3 for the coli and 5 for the streptococcus. One hundred readings were obtained for each test suspension using each method. When suspensions containing y × 10 5 , y × 10 6 and y × 10 7 organisms/ml were tested, satisfactory results were obtained using the loop, Orion and Urostrip methods. However, with Microstix some falsely low readings were obtained, and it was not possible to distinguish between the concentrations. When suspensions containing y × 10 4 organisms/ml were tested, the percentages of correct readings for the loop, Orion, Urostrip and Microstix methods were 98%, 85%, 60% and 38% respectively. A similar order of accuracy was obtained for suspensions containing y × 10 3 organisms/ml. Most Urostrip errors consisted of the streptococcus suspensions being read too high, while most Microstix errors consisted of the coli suspensions being read too high. For laboratory use, the loop appears to be the most reliable method and has the additional advantages of separating colonies even when the bacterial concentration is high, and of allowing dilution of antibiotic effect. Where transport of specimens is a problem, the agar dip slide seems to be the method of choice.

Effects of coitus on gonadotropin, prolactin and sex steroid levels in man.

ABSTRACT Coitus occurring at days 10–13 of the menstrual cycle was shown to have no effect on serum levels of FSH, LH and GH in 6 healthy married couples aged 24–41 years. Serum levels of progesterone and estradiol in the women and testosterone levels in the men were also unchanged up to 1 hr following coitus. In contrast, 2 of 6 women had 8–10-fold increments in serum prolactin levels within 10 min following coitus. There was no change in serum prolactin levels in the remaining 4 women and 6 men. Thus, there is no evidence that reflex gonadotropin release or ovulation occurs following coitus in man. Coitus and/or accompanying breast manipulation may result in prolactin release in women.