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PubMed2006

Biochemical and pharmacological properties of an allosteric modulator site of the human P-glycoprotein (ABCB1).

The drug-transport function of the human P-glycoprotein (Pgp or ABCB1) is inhibited by a number of structurally unrelated compounds, known as modulators or reversing agents. Among them, the thioxanthene derivative flupentixol inhibits Pgp-mediated drug transport by an allosteric mechanism. Unlike most other Pgp modulators, the cis isomer of flupentixol [cis-(Z)-flupentixol] facilitates interaction of Pgp with its transport-substrate [125I]iodoarylazidoprazosin (or [125I]IAAP), yet inhibits transport. In this study, we show that the flupentixol site acts as a common site of interaction for the tricyclic ring-containing modulators thioxanthenes and phenothiazines. The allosteric stimulation of [125I]IAAP binding to Pgp occurs independent of the phosphorylation status of the transporter. Stimulation is retained in purified Pgp reconstituted into proteoliposomes, suggesting no involvement of any other cellular protein in the phenomenon. However, perturbation of the lipid environment of the reconstituted Pgp by nonionic detergent octylglucoside abolishes stimulation by cis-(Z)-flupentixol of [125I]IAAP binding. Extensive trypsin digestion of the [125I]IAAP-labeled Pgp generates a 5.5 kDa fragment with 80% of the stimulated level of labeling associated with it. Sensitivity to inhibition by transport-substrate vinblastine and competitive modulator cyclosporin A suggests that the elevated level of [125I]IAAP binding to the fragment represents a functionally relevant interaction with the substrate site of Pgp. In summary, we demonstrate that allosteric modulation by cis-(Z)-flupentixol is mediated through its interaction with Pgp at a site specific for tricyclic ring-containing Pgp modulators of thioxanthene and phenothiazine backbone, independent of other cellular components and the phosphorylation status of the protein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Role of tyrosine residues in modulation of claudin-4 by the C-terminal fragment of Clostridium perfringens enterotoxin.

The C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) modulates the barrier function of claudin-4 via its C-terminal 16 amino acids. In the current study, we investigated the roles of tyrosine residues (Y306, Y310 and Y312) in this region in the modulation of TJs by C-CPE. Single mutations of Y306, Y310 and Y312 to alanine resulted in partial reduction of claudin-4 binding. We also prepared double mutants of C-CPE to further evaluate the roles of these tyrosine residues. Replacement of Y310 and Y312 with alanine (Y310A/Y312A) partly reduced the ability of C-CPE to bind to claudin-4. Double mutants Y306A/Y310A and Y306A/Y312A, however, lost the ability to bind to claudin-4 and to modulate the TJ barrier. We also found that a triple mutant (Y306A/Y310A/Y312A) lost the ability to bind claudin-4, modulate the TJ barrier, and enhance jejunal absorption in rats. These results indicate that tyrosines 306, 310, and 312 are critical for the interaction of C-CPE with claudin-4 and for the modulation of TJ barrier function by C-CPE. This study provides information that should help in the development of claudin modulators based on C-CPE.

Base Sequence↗
PubMed2004

Direct resistively heated column gas chromatography (Ultrafast module-GC) for high-speed analysis of essential oils of differing complexities.

This study applies Ultrafast module-GC (UFM-GC) with direct resistively heated columns to routine analysis of a group of essential oils of differing complexities (chamomile, peppermint, rosemary and sage). Essential oils were analysed by conventional GC with conventional inner diameter (i.d.) columns (0.25 mm) of different lengths (5 and 25 m long) and by Fast GC and Ultrafast module-GC with narrow bore columns (0.1 mm i.d., 5 m long). Column performance were evaluated and compared through their Grob test, separation number and peak capacity. Ultrafast module-GC was successful in the qualitative and quantitative analysis of essential oils of different compositions with analysis times between 40 s and 2 min versus 20-60 min required by conventional GC. Critical pairs or groups of components were separated by carefully tuning selectivity of the stationary phase to compensate for loss of efficiency due to the use of short columns and high temperature rates. The Ultrafast module-GC results of peppermint e.o. analyses were also validated and compared to those obtained by conventional GC; by measuring precision over time (i.e. repeatability and intermediate precision) and accuracy. Ultrafast module-GC showed a good separation reproducibility affording reliable component identification through the relative retention times and quantitative determination through normalised peak areas. Accuracy data also showed that Ultrafast module-GC and conventional GC normalised areas and areas percentage were perfectly comparable.

Chromatography, Gas↗
PubMed2004

Tempo dependence of middle- and long-latency auditory responses: power and phase modulation of the EEG at multiple time-scales.

OBJECTIVE: We measured the influences of power and phase modulations of neuroelectric activity on auditory responses to pure-tone patterns with inter-onset intervals typical of music. METHODS: Tones were presented to 8 subjects at 10 different tempos from 150 to 3125 ms and with random intervals. We quantified time-frequency (TF) power with respect to a pre-tone-onset baseline and the TF phase coherence across trials. Peak-to-peak event-related potential (ERP) amplitude values for the middle and long-latency auditory responses were obtained for comparison. RESULTS: ERP amplitude, size of power modulation, and amount of phase coherence were larger at slower tempos for the long-latency response (LLR) but not for the middle-latency response (MLR). Multiple regression analysis indicated that for MLR and LLR, phase modulation was a better predictor of ERP amplitude than power modulation. CONCLUSIONS: Phase modulation is a better predictor of ERP amplitude than power modulation for middle and long-latency auditory responses. SIGNIFICANCE: Lack of diminution of the MLR at fast tempos indicates its usefulness for studying early cortical processing of music and speech patterns.

Acoustic Stimulation↗
PubMed2006

Predictability of the target stimulus for sensory-guided movement modulates early somatosensory cortical potentials.

OBJECTIVE: To investigate the role of sensory modulation in the control of sensory-guided behaviour. Specifically, we hypothesized that early somatosensory evoked potentials (SEPs) would be facilitated during performance of continuous sensory-guided movement requiring sustained attention. METHODS: Median nerve SEPs were elicited via electrical stimulation and recorded from scalp electrodes while subjects performed tasks requiring continuous sensory-motor transformations. Subjects received a predictable (rhythmic amplitude modulation) or unpredictable (random amplitude modulation) amplitude varying tactile stimulus (frequency constant at 20 Hz) delivered to the tip of the index finger either alone or with the requirement to track it by modulating the isometric grip force produced by the opposite hand. RESULTS: Early SEP (N20-P27) amplitudes were differentially modulated during unpredictable tracking compared to sensory-motor controls. Specifically, N20 amplitudes were attenuated and P27 amplitudes were enhanced during sensory-guided tracking. CONCLUSIONS: Sustained attention to task-relevant sensory stimuli differentially modulates areas within primary somatosensory cortex (S1) during a continuous sensory-motor transformation. SIGNIFICANCE: These data have implications for understanding the role of attention in regulating somatosensory cortices during sensory-motor behaviour.

Adult↗
PubMed2006

Nonexcitatory, cardiac contractility modulation electrical impulses: feasibility study for advanced heart failure in patients with normal QRS duration.

BACKGROUND: Cardiac contractility modulation signals are associated with acutely improved hemodynamics, but chronic clinical impact is not defined. OBJECTIVES: The purpose of this randomized, double-blind, pilot study was to determine the feasibility of safely and effectively delivering cardiac contractility modulation signals in patients with heart failure. METHODS: Forty-nine subjects with ejection fraction <35%, normal QRS duration (105 +/- 15 ms), and New York Heart Association (NYHA) class III or IV heart failure despite medical therapy received a cardiac contractility modulation pulse generator. Patients were randomized to have their devices programmed to deliver cardiac contractility modulation signals (n = 25, treatment group) or to remain off (n = 24, control group) for 6 months. Evaluations included NYHA class, 6-minute walk, cardiopulmonary stress test, Minnesota Living with Heart Failure Questionnaire, and Holter monitoring. RESULTS: Although most baseline features were balanced between groups, ejection fraction (31.4% +/- 7.4% vs 24.9% +/- 6.5%, P = .003), end-diastolic dimension (52.1 +/- 21.4 mm vs 62.5 +/- 6.2 mm, P = .01), peak VO(2) (16.0 +/- 2.9 mL O(2)/kg/min vs 14.3 +/- 2.8 mL O(2)/kg/min, P = .02), and anaerobic threshold (12.3 +/- 2.5 mL O(2)/kg/min vs 10.6 +/- 2.4 mL O(2)/kg/min, P = .01) were worse in the treatment group than in the control group. Nevertheless, one death occurred in the control group, and more patients in the treatment group were free of hospitalization for any cause at 6 months (84% vs 62%). No change in ectopy was observed. Compared with baseline, 6-minute walk (13.4 m), peak VO(2) (0.2 mL O(2)/kg/min), and anaerobic threshold (0.8 mL O(2)/kg/min) increased more in the treatment group than in control. None of these differences were statistically significant (small sample size). NYHA and Minnesota Living with Heart Failure Questionnaire changed similarly in the two groups. CONCLUSION: Despite a sicker population in the treatment group, no specific safety concerns emerged with chronic cardiac contractility modulation signal administration. Further study is required to definitively define the safety and efficacy of cardiac contractility modulation signals.

Aged↗
PubMed2005

Amplitude modulation of gamma band oscillations at alpha frequency produced by photic driving.

Gamma band response to visual stimulation in humans has been observed to have both burst and resonance properties. Amplitude modulation of gamma activity at low frequencies has been seen in rat hippocampus and modeled in a number of forms. Significant amplitude modulation (p=0.05) of 33 Hz gamma frequency activity at the frequency of an 8 1/3 Hz photic driving stimulus, which also produced strong alpha entrainment, was observed in 67% of the channels in 42 human subjects. Similar amplitude modulation was found at a range of frequencies from greater than 50 Hz to about 28 Hz. The peak of the gamma amplitude modulation curve trailed the peak of the alpha signal by 25 to 30 ms, corresponding to a phase difference of 150 degrees to 180 degrees. The phase consistency of the gamma signal, measured across comparable times of the alpha signal, was least at the minimum amplitude modulation, and largest at the maximum. Although there was no consistent overall relation between the gamma amplitude and alpha amplitude, peak gamma amplitude values were consistently higher during post-target-stimulus alpha suppression, which occurs about 300-750 ms subsequent to stimulus presentation, than they were at the time of maximum alpha activity during the immediate post-stimulus period. It is hypothesized that there is an interaction between the alpha and gamma generating systems, in which gamma triggers alpha activity and is subsequently inhibited by it, thus producing the observed amplitude modulation. The transition from dark to light of the photic driving stimulus begins a phase resetting process in the gamma system and a concomitant burst of gamma activity; this produces an activation in the alpha system, similar to that found in the P1-N1 response in evoked potential experiments, and a subsequent inhibition of gamma production.

Adult↗
PubMed2005

Upper stability island of the quadrupole mass filter with amplitude modulation of the applied voltages.

Modulation of the voltages applied to a quadrupole mass filter (QMF), either RF or RF and DC, leads to splitting of the stability region into islands of stability. The ion optical properties, such as transmission, resolving power and peak tails of the first upper stability islands have been investigated by numerical simulation of ion trajectories. The dependence of the location of this island on the amplitude of the modulation and the parameter nu = omega/Omega = Q/P where omega is modulation frequency, Omega is main angular radio frequency, and Q and P are integers, is calculated in detail. Different methods of adjusting the QMF resolution are examined. It is found that operation at the upper and lower tips of the stability islands created by amplitude modulation of the RF voltage is preferred, because of the technical simplicity of this method and a reduction of the required separation time. Amplitude modulation improves the performance of a QMF constructed with round rods, in comparison to perfect quadrupole fields. For example, with amplitude modulation of the RF, to reach a resolution of R(0.1) = 1200 requires only about 75 RF cycles of ion motion in a quadrupole field created by round rods.

Journal Article↗
PubMed2006

Assemblage of novel release modules for the development of adaptable drug delivery systems.

The aim of this paper was to study the applicability of the release module assemblage technology for an adaptable control of drug delivery rate and site. The elementary release module was a swellable matrix having one base convex and the other concave, named Dome Matrix. The swelling and release behavior of the release module was studied. The presence of the convex and concave bases in the swellable matrix slightly changed the overall drug delivery kinetics exhibited by a flat base cylindrical matrix having the same weight and composition. The swelling and drug release of the individual bases of the matrix was also studied to investigate the effect of the surface shape. The concave, convex and flat bases exhibited different swelling and release kinetics. The convex base released drug at faster rate than the concave base, whereas the flat base was intermediate. The release mechanisms of convex and concave bases were significantly different. The Dome Matrix module was selected for assembling several modules in a delivery system obtained by a guided insertion of the convex base into the concave base or by concave/concave base sticking. The module assemblage shows different drug release behavior depending on the geometry of assembled systems.

Delayed-Action Preparations↗
PubMed2006

Head module control of mediator interactions.

Yeast Mediator proteins interacting with Med17(Srb4) have been expressed at a high level with the use of recombinant baculoviruses and recovered in homogeneous form as a seven subunit, 223 kDa complex. Electron microscopy and single-particle analysis identify this complex as the Mediator head module. The recombinant head module complements "headless" Mediator for the initiation of transcription in vitro. The module interacts with an RNA polymerase II-TFIIF complex, but not with the polymerase or TFIIF alone. This interaction is lost in the presence of a DNA template and associated RNA transcript, recapitulating the release of Mediator that occurs upon the initiation of transcription. Disruption of the head module in a temperature-sensitive mutant in vivo leads to the release of middle and tail modules from a transcriptionally active promoter. The head module evidently controls Mediator-RNA polymerase II and Mediator-promoter interactions.

Baculoviridae↗
PubMed2005

Early modulation of visual cortex by sound: an MEG study.

Sound can alter visual perception. This has been recently demonstrated by a strong illusion in which a single flash is perceived as multiple flashes when accompanied by multiple brief sounds. While psychophysical findings on this sound-induced flash illusion indicate that the modulations of visual percept by sound occur at a perceptual processing level, it remains unclear at what level of perceptual processing these interactions occur and what mechanisms mediate them. Here we investigated these questions using MEG. We found modulation of activity in occipital and parietal scalp locations, when comparing illusion trials with visual-alone and auditory-alone trials. This modulation occurred as early as 35-65 ms from the onset of the visual stimulus. Activity was also modulated in the occipital and parietal areas as well as anterior areas at a later ( approximately 150 ms post-stimulus) onset. No significant interactions were observed in occipital and parietal areas in trials in which illusion was not perceived. These results indicate that the auditory alteration of visual perception as reflected by the illusion is associated with modulation of activity in visual cortex. The early onset of these modulations suggests that a feed-forward or lateral circuitry is at least partially involved in these interactions.

Acoustic Stimulation↗
PubMed2005

Mechanisms of allosteric modulation at GABAB receptors by CGP7930 and GS39783: effects on affinities and efficacies of orthosteric ligands with distinct intrinsic properties.

We determined the effects of the allosteric gamma-aminobutyric acid B receptor modulators CGP7930 and GS39783 on binding and function of orthosteric ligands with distinct intrinsic properties. In radioligand binding (saturation or displacement) experiments, the affinities of a number of competitive antagonists were decreased by the modulators, with no change in receptor number. The binding curves of the partial agonist CGP47656 comprised a high and a low affinity component; the affinity of the former was increased by the allosteric agents. The maximal stimulation of GTP[gamma](35)S binding via recombinant GABA(B) receptors by CGP47656 was increased 4-fold in the presence of 30 microM CGP7930 or GS39783. Two compounds known so far as "silent" competitive GABA(B) receptor antagonists, CGP35348 and 2-OH-saclofen, did not stimulate GTP[gamma](35)S binding on their own, but became low efficacy partial agonists in the presence of the two modulators. The potency of GABA to inhibit the formation of cAMP induced by a forskolin analog in a recombinant CHO cell line expressing GABA(B) receptors was increased by the modulators. CGP35348 and 2-OH-saclofen, like CGP47656, were partial agonists on their own in this assay, and the allosteric modulators increased the potency as well as the efficacy of all three compounds. With CGP52432, there was a trend towards inverse agonism in the cAMP assay. These results show that the intrinsic properties of orthosteric ligands are highly dependent on the characteristics of the assay system used and that allosteric modulators are useful tools for elucidating these properties.

Allosteric Regulation↗
PubMed2005

Role of the alpha subunit in the modulation of GABA(A) receptors by anabolic androgenic steroids.

Neural transmission mediated by circuits expressing alpha2 subunit-containing gamma-aminobutyric acid type A (GABA(A)) receptors is critical for the expression of behaviors known to be altered by anabolic androgenic steroids (AAS). Here we show that micromolar concentrations of AAS, which reflect levels found in steroid abusers, induce positive modulation of currents from alpha2beta3 gamma2L recombinant receptors elicited by pulses of GABA that mimic synaptic conditions in a manner that is mechanistically distinct from modulation induced at alpha1beta3 gamma2L receptors. Specifically, at alpha2-containing receptors, the AAS, 17alpha-methyltestosterone (17alpha-MeT) enhanced peak current, slowed deactivation, diminished desensitization, and promoted entry of receptors into more distal states along the activation pathway. Analysis of GABA(A) receptor-mediated synaptic currents in primary cortical neurons followed by single cell real-time RT-PCR demonstrated that 17alpha-MeT enhancement of synaptic currents is proportional to the ratio of alpha2 to alpha1 subunit mRNA. Finally, we show that the modulation elicited by AAS is not comparable to that produced by micromolar concentrations of other positive allosteric modulators at alpha2-containing receptors. In sum, these data indicate that AAS elicit effects on GABA(A) receptor function that depend significantly on alpha subunit composition and that the mechanism of AAS modulation of GABA(A) receptors is distinct from that of other positive allosteric modulators.

Anabolic Agents↗
PubMed2004

Modulation of AMPA receptor kinetics differentially influences synaptic plasticity in the hippocampus.

Prior studies showed that positive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor modulators facilitate long-term potentiation (LTP) and improve the formation of several types of memory in animals and humans. However, these modulators are highly diverse in their effects on receptor kinetics and synaptic transmission and thus may differ also in their efficacy to promote changes in synaptic strength. The present study examined three of these modulators for their effects on synaptic plasticity in field CA1 of hippocampal slices, two of them being the benzamide drugs 1-(quinoxalin-6-ylcarbonyl)piperidine (CX516) and 1-(1,4-benzodioxan-6-ylcarbonyl)piperidine (CX546) which prominently enhance synaptic transmission yet differ in their relative impact on amplitude versus duration of the synaptic response. The third drug was cyclothiazide which potently blocks AMPA receptor desensitization. Effects on plasticity were assessed by measuring (i) the likelihood of obtaining stable potentiation when using theta-burst stimulation with three instead of four pulses per burst, (ii) the maximum amount of potentiation under optimal stimulation conditions, and (iii) the effect on long-term depression (LTD). Both benzamides facilitated the formation of stable potentiation induced with three-pulse burst stimulation which is normally ineffective. CX546 in addition increased maximally inducible potentiation after four-pulse burst stimulation from about 50% to 100%. Burst response analysis revealed that CX546 greatly prolonged the duration of depolarization by slowing the decay of the response which thus presumably leads to a more continuous N-methyl-D-aspartate (NMDA) receptor activation. Cyclothiazide was ineffective in increasing maximal potentiation in either field or whole-cell recordings. CX546, but not CX516, also enhanced nearly two-fold the NMDA receptor-dependent long-term depression induced by heterosynaptic 2 Hz stimulation. Tests with recombinant NMDA receptors (NR1/NR2A) showed that CX516 and CX546 have no direct effects on currents mediated by these receptors. These results suggest that (1) modulation of AMPA receptors which increases either response amplitude or duration can facilitate LTP formation, (2) modulators that effectively slow response deactivation augment the maximum magnitude of LTP and LTD, and (3) receptor desensitization may have a minor impact on synaptic plasticity in the hippocampus. Taken together, our data indicate that AMPA receptor modulators differ substantially in their ability to enhance synaptic potentiation or depression, depending on their particular influence on receptor kinetics, and hence that they may also be differentially effective in influencing higher-order processes such as memory encoding.

Animals↗
PubMed2005

Modulation of available vesicles and release kinetics at the inhibitor of the crayfish neuromuscular junction.

We have investigated the effect of serotonin (5-HT) and okadaic acid (OA) on presynaptic processes at the crayfish inhibitory neuromuscular junction. Two different physiological parameters of transmitter release were examined: release kinetics and the size of the readily releasable pool of vesicles (RRP). Using a paired pulse stimulus and high frequency trains, we established that a single broad action potential, recorded in 20 mM tetraethylammonium and 1 mM 4-amino-pyridine, released the RRP in its entirety. Thus, by measuring the amplitude of inhibitory postsynaptic potential (IPSC) we were able to directly assess the effects of 5-HT and OA on the RRP. Serotonin at 200 nM and OA at 2.5 microM each significantly increased IPSC above control levels and the effects of these two modulators were comparable. Both modulators also induced a leftward shift in the rising phase of IPSC, i.e. an apparent acceleration in release kinetics. The shift caused by OA was significantly more pronounced than that induced by 5-HT. This apparent acceleration in release was not associated with a corresponding change in the presynaptic Ca2+ transient measured at a 2 kHz resolution, suggesting that modulation was not due to an acceleration in Ca2+ channel kinetics. In view of the comparable increase in the size of the RRP by the modulators, the differential modulation of release kinetics suggests that these two parameters may be modulated by separate biochemical processes.

4-Aminopyridine↗
PubMed2006

Definition, expression, and characterization of a protein domain in the N-terminus of pregnancy-associated plasma protein-A distantly related to the family of laminin G-like modules.

Although pregnancy-associated plasma protein-A (PAPP-A), a modulator of insulin-like growth factor (IGF) activity through its cleavage of IGF-binding protein (IGFBP)-4 and -5, has been known for more than two decades, knowledge about its domain architecture is still incomplete. Using position-specific iterative BLAST, we have identified distant relatives of the PAPP-A N-terminal sequence stretch of 250 residues. We present evidence that a protein domain with weak similarity to known laminin G-like (LG) modules is contained within this region, and we propose that PAPP-A and PAPP-A2 are new and unique members in the group of LG proteins as the pappalysins represent the first examples where LG modules are associated with proteinases. Fourteen beta-strands characteristic for the LG structure were tentatively located within the PAPP-A LG (PA-LG) module using secondary structure prediction and sequence alignment. Upon mammalian expression of PAPP-A truncation mutants, we defined domain boundaries showing that PA-LG is an autonomously folding unit, which spans the first 243 residues. We were unable to express PAPP-A variants which lack the PA-LG module, suggesting a possible role in stabilization of the proteolytic domain. To obtain larger amounts of protein for functional and structural analysis, the defined PA-LG domain was expressed in bacteria and folded in vitro. In addition, the availability of recombinant PA-LG module may potentially improve diagnostic assays based on the measurement of PAPP-A antigen, and also facilitate the study of PAPP-A in animal model systems.

Amino Acid Sequence↗
PubMed2004

Modulation of resistance to regional chemotherapy in the extremity melanoma model.

BACKGROUND: The presence of resistance to chemotherapy is associated with poor tumor response and patient survival in a variety of tumors. Attempts to modulate resistance in conjunction with systemic chemotherapy have been limited by the toxicity of combined therapy, particularly gastrointestinal or hematopoetic toxicity. This study explored systemic modulation of resistance in conjunction with intra-arterial regional therapy to determine if tumor responses to melphalan could be improved with acceptable toxicity. METHODS: Using a nude rat human xenograft model of extremity melanoma,we analyzed tumors for glutathione (GSH), the main protein in the melphalan resistance pathway. Modulation of GSH was performed with intraperitoneal buthionine sulfoximine (BSO). In parallel, BSO-modulated and nonmodulated animals underwent survival studies after regional intra-arterial perfusion with melphalan or saline. Rats were monitored daily for tumor growth and toxicity. RESULTS: BSO depleted tumor GSH levels by 71.8% with minimal toxicity. Survival studies using increasing melphalan concentrations demonstrated similar tumor growth. The combined use of modulator and chemotherapeutic agent showed a significant tumor growth delay as compared to control and drug-alone group without enhanced toxicity. CONCLUSIONS: Modulation of resistance in conjunction with regional chemotherapy allows for improved tumor responses with minimal toxicity. These results demonstrate that BSO can potentiate the cytotoxic effects of regional melphalan therapy in the setting of extremity melanoma.

Animals↗
PubMed1999

Response of obstetrics and gynecology program directors to a domestic violence lecture module.

OBJECTIVE: Our goal was to determine the use by obstetrics and gynecology residency program directors of The American College of Obstetricians and Gynecologists' domestic violence slide lecture module and the opinions of the directors regarding its efficacy. STUDY DESIGN: A 6-question survey was mailed to 289 directors of accredited obstetrics and gynecology programs in the United States and Canada 9 and 13 months after a learning module on domestic violence was mailed to these same persons. The questions related to receipt and use of the module in the curriculum, target audiences, future plans for integration of the module into curricula, and recommendations for future supplemental topics in the same format. RESULTS: The return rate for the survey was 57% (164/289). The responses represented university-affiliated, community- and military-based programs with representation from all geographic areas of the country. Fourteen directors who had no recollection of receiving the package were sent a second set. The lecture had been presented by 72% of the respondents' departments to audiences of residents (89%), medical students (55%), practicing physicians (41%), and the lay public (11%). Two thirds of the nonusers and 87% of the users intended to use the module as a formal lecture in the curriculum of both residents and medical students in the coming school year. Recommendations for future supplemental lecture packages included abuse during pregnancy, screening women with different cultural backgrounds, and how to ask tough questions. CONCLUSION: The majority of obstetrics and gynecology resident program directors who responded to the survey integrated or will integrate an American College of Obstetricians and Gynecologists-created learning module on domestic violence into their residents' and medical students' formal curricula.

Community Health Services↗