Sexual activity and functioning in ovarian cancer survivors: an internet-based evaluation.

OBJECTIVES: Sexual dysfunction is a known complication of treatment for many cancers, but there have been relatively few studies investigating outcomes for ovarian cancer survivors. We have previously reported that women treated for ovarian cancer experience persistent psychological and physical problems. Sexual functioning was highlighted as a significant factor and we sought to investigate this further. METHODS: Women were invited to complete a questionnaire using both paper and online response formats. A validated tool, the Sexual Activity Questionnaire, was used to obtain information from women following a diagnosis of ovarian cancer. RESULTS: Across all responders (n = 102, mean age 51.3 years), 63% of women reported their ovarian cancer diagnosis had negatively changed their sex life. The most common reasons given for an absence of sexual activity were a lack of interest in sex, physical problems that prevented sex or no partner. Of the 46% of responders who stated they were sexually active, 77% reported pain or discomfort during intercourse and 87% described vaginal dryness. CONCLUSION: For the majority of women, treatment for ovarian cancer negatively impacts on their sex lives. Many of the symptoms described by participants are potentially reversible and clinicians should be open to raising the issue of sexual functioning with their patients.

Computational modeling of flow and gas exchange in models of the human maxillary sinus.

The present study uses numerical modeling to increase the understanding of sinus gas exchange, which is thought to be a factor in sinus disease. Order-of-magnitude estimates and computational fluid dynamics simulations were used to investigate convective and diffusive transport between the nose and the sinus in a range of simplified geometries. The interaction between mucociliary transport and gas exchange was modeled and found to be negligible. Diffusion was the dominant transport mechanism for small ostia and large concentration differences between the sinus and the nose, whereas convection was important for larger ostia or smaller concentration differences. The presence of one or more accessory ostia can increase the sinus ventilation rate by several orders of magnitude, because it allows a net flow through the sinus. Estimates of nitric oxide (NO) transport through the ostium based on measured sinus and nasal NO concentrations suggest that the sinuses cannot supply all the NO in nasally exhaled air.

Case report: Rutherfurd syndrome associated with Marfan syndrome.

BACKGROUND: Rutherfurd syndrome is a rare genetic disorder that is primarily characterised by the classical triad of gingival fibromatosis, delayed tooth eruption and corneal dystrophy. Associated features of the condition include abnormally shaped teeth, mental retardation and aggressive behaviour. CASE REPORT: His Consultant Clinical Geneticist referred a 2-year-old boy to the Dept. of Paediatric Dentistry at Manchester Dental Hospital. The child and his father had a diagnosis of Rutherfurd Syndrome; a rare autosomal-dominant condition featuring corneal dystrophy, gingival hypertrophy, abnormally shaped teeth and delayed eruption. The only erupted teeth were 52, 71 and 81. The patient also suffers from features of Marfan syndrome, a condition he has inherited from his mother. CLINICAL MANAGEMENT: Preventive advice was provided and the patient was placed on regular review. By the age of 4 years, 52, 61, 72, 71 and 81 were the only teeth present clinically. Maxillary and mandibular dentures were provided, which he refused to wear. FOLLOW-UP: At age 8 years, 31 and 41 were erupted lingual to the primary incisors. No other permanent teeth had erupted. Radiographs revealed failure of eruption of multiple primary and permanent teeth. The second premolars had formed above the unerupted mandibular primary second molars. The patient continued to refuse any intervention. Treatment options discussed included overdentures and /or removal of primary teeth and exposure of permanent teeth. CONCLUSION: This case has presented a rare syndrome with two important dental features, namely gingival hyperplasia and failure of eruption. The case has a long term follow up of 6 years and has a first time association to Marfan syndrome. It also highlights the importance of family history and how it can affect the attitude of the child towards dental treatment.

Miniature LiF:Mg,Cu,P TLDs to study the effect of applicator material in 192-Ir brachytherapy.

Dose calculations in brachytherapy planning typically don't take into account inhomogeneities and the material of applicators. We evaluated the justification of the latter by investigating the dose delivered in 192-Ir interstitial implants employing plastic catheters and steel needles using miniature LiF:Mg,Cu,P thermoluminescence dosimeters (TLDs) which fit in the applicators. Within the uncertainty of the measurement (+/- 5%) no difference could be found in the dose distribution from 192Ir in steel needles or plastic catheters. Computerized treatment planning (Philips/ADAC Pinnacle) was in good agreement with the measured data.

Selection of GM2, fucosyl GM1, globo H and polysialic acid as targets on small cell lung cancers for antibody mediated immunotherapy.

Glycolipids GM2, GD2, GD3, fucosyl GM1, sialyl Lewis a (sLe(a)) and globo H, and polysialic acid on embryonal NCAM, are cell-surface antigens expressed on small cell lung cancer (SCLC) biopsy specimens. They are all candidates for inclusion in a polyvalent, antibody-inducing vaccine or for adoptive therapy with monoclonal antibodies (mAbs) against SCLC. To identify the minimum optimal combination of target antigens on SCLC and to confirm that antibodies against this combination might be able to mediate complement activation and lysis in the majority of cases, we tested ten SCLC cell lines with fluorescence activated cell sorter (FACS) and complement dependent cytotoxicity (CDC) assays using mAbs against these seven target antigens individually or pooled in different combinations. We find that (1) none of these mAbs demonstrated strong FACS reactivity with more than 6 of the 10 cell lines, (2) no mAb had strong CDC reactivity with more than 4 of the cell lines, (3) when the mAbs were pooled, nine cell lines were strongly positive by FACS and nine cell lines were strongly positive by CDC, and (4) mAbs against GM2, FucGM1, globo H and polysialic acid was the minimum optimal combination for inducing FACS reactivity. The addition of mAbs against sLe(a), GD2 and GD3 had no additional impact by FACS and only minimal additional impact in CDC assays. H345, the only cell line that had less than 30% CDC with the four mAb pool was strongly positive by FACS. To understand the lack of correlation between FACS and CDC in the case of H345, the ten cell lines were screened for expression of complement resistance factors CD55 and CD59. Three cell lines were strongly positive for CD55 and eight were strongly positive for CD59. Overall, no correlation was seen between expression of either of these factors on the ten cell lines and sensitivity to CDC. In the case of H345 however, complement resistance of H345 is demonstrated to be mediated primarily by CD59, and in the presence of mAb against CD59, the four mAb MEM-43 pool induced strong (94%) CDC. CD59 inhibits membrane attack complex formation but not activation of earlier complement components. Consequently, all ten cell lines are good targets for complement activation by the four antibody pool and for elimination by effector mechanisms including complement mediated inflammation and opsonization. These findings support our plan to develop a tetravalent vaccine against SCLC targeting GM2, fucosyl GM1, globo H and polysialic acid.

Facial characterization of infants with cleft lip and palate using a three-dimensional capture technique.

OBJECTIVE: To characterize the soft tissue features of infants with unilateral cleft lip (UCL) and unilateral complete cleft lip and palate (UCLP) prior to primary surgery and compare with noncleft controls. DESIGN: Prospective controlled capture of the facial morphology of infants using a noninvasive three-dimensional stereophotogrammetry method. PARTICIPANTS: 23 children with presurgical cleft: 11 UCL (M = 6, F = 5); 12 UCLP (M = 9, F = 3), and 21 noncleft controls (M = 7, F = 14) were imaged at approximately 3 months of age (range 10 to 16 weeks). MAIN OUTCOME MEASURE: Accurate, repeatable quantification of facial soft tissues in infants with clefts prior to surgery. RESULTS: Significant differences (p <.05) were found between the UCLP group and UCL and control groups in anatomical and soft nose width, cleft-side alar wing length, and nasal tip horizontal displacement. Both cleft groups were significantly different from controls and from each other in cleft-side nostril dimensions, alar wing angulation, columella angle, and alar base to corner of mouth dimension; alar base width; and soft tissue defect in nose and the lip and philtrum length bordering the cleft. Significant differences between clefts and controls were identified in the nostril and philtrum on the noncleft side. CONCLUSIONS: The use of children with UCL as controls for UCLP studies is inappropriate. This technique overcame the limitations of direct measurement of infant faces to aid the surgeon in the planning and subsequent re-evaluation of surgical rationale.

Varicella-zoster virus-infected human sensory neurons are resistant to apoptosis, yet human foreskin fibroblasts are susceptible: evidence for a cell-type-specific apoptotic response.

The induction of apoptosis or programmed cell death in virus-infected cells is an important antiviral defense mechanism of the host, and some herpesviruses have evolved strategies to modulate apoptosis in order to enhance their survival and spread. In this study, we examined the ability of varicella-zoster virus (VZV) to induce apoptosis in primary human dorsal root ganglion neurons and primary human foreskin fibroblasts (HFFs). Three independent methods (annexin V, TUNEL [terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling] staining, and electron microscopy) were used to assess apoptosis in these cells on days 1, 2, and 4 postinoculation. By all three methods, apoptosis was readily detected in VZV-infected HFFs. In stark contrast, apoptosis was not detected during productive VZV infection of neurons. The low-passage clinical isolate Schenke and the tissue culture-adapted ROka strain both induced apoptosis in HFFs but not in neurons, suggesting that this cell-type-specific apoptotic phenotype was not VZV strain specific. These data show that the regulation of apoptosis differs markedly between HFFs and neurons during productive VZV infection. Inhibition of apoptosis during infection of neurons may play a significant role in the establishment, maintenance, and reactivation of latent infection by promoting survival of these postmitotic cells.

Validation of a vision-based, three-dimensional facial imaging system.

OBJECTIVE: The aim of this study was to assess the accuracy of a newly developed three-dimensional (3D) imaging system in recording facial morphology. METHODS: Twenty-one infants with cleft lip each had a full-face alginate impression taken at the time of primary lip repair, and a stone cast was constructed from each impression. Five anthropometric points were marked on each cast. Each cast was digitized, and the 3D co-ordinates of the five points were obtained using a co-ordinate measuring machine (CMM, Ferranti) of documented accuracy (9.53 microm). Each cast was scanned in four positions using a computerized stereophotogrammetry (C3D) system. The five points were located on the 3D images, and their 3D co-ordinates were extracted by three operators. The co-ordinate systems produced by C3D were aligned, via translation and rotation, to match the CMM co-ordinate system using partial ordinary procrustes analysis. The displacements of the adjusted C3D co-ordinates from the reference co-ordinates were then measured. Three different types of errors were identified: operator, system, and registration errors. RESULTS: Operator error was within 0.2 mm of the true co-ordinates of the landmarks. C3D was accurate within 0.4 mm. The average displacement of points over the 21 casts at four positions for the three operators was 0.79 mm (median 0.68). CONCLUSIONS: The presented 3D imaging system is reliable in recording facial deformity and could be utilized in recording cleft deformities and measuring the changes following surgery

Facial asymmetry--3D assessment of infants with cleft lip & palate.

OBJECTIVES: To determine the degree of facial asymmetry in infants with unilateral cleft lip and/or palate, and quantify improvements following primary surgery, in three dimensions. DESIGN: The faces of 20 infants with unilateral clefts (10 UCL; 10 UCLP), and 20 age-matched, non-cleft controls, were captured using the C3D stereophotogrammetry system prior to primary lip/nose repair (at 3 months), at 6 months and at age 1 year. METHODS: Procrustes techniques were applied to 3D landmark configurations to its mirror image. Mean squared distances between landmarks and their antimeres were calculated and expressed as asymmetry scores for each 3D configuration. Full-face, nose and lip median scores were compared and changes with time evaluated (P < 0.01). RESULTS: There were no significant changes in asymmetry scores in the control group from 3 months to 1 year. The UCLP group was more asymmetric than the UCL group, displaying greatest improvement in nasal symmetry following primary repair. The lips continued to improve over time. The UCL group had significant nasal asymmetry, which did not appear to improve with primary surgery. CONCLUSIONS: Immediate improvement in asymmetry scores in children with UCLP is related to the production of a more symmetrical nasal form after primary surgery. In contrast, the nasal asymmetry seen in children with UCL is unchanged despite surgery. Full face asymmetry scores may mask subtle changes over time. Nasal and lip asymmetry should be considered individually.

LiF:Mg,Cu,P 'pin worms': miniature detectors for brachytherapy dosimetry.

Dose measurements in brachytherapy 192Ir implants are often difficult due to large dose gradients and complex photon spectra. Therefore, tissue-equivalent detectors with a high spatial resolution, such as the highly promising LiF:Mg,Cu,P thermoluminescent detectors (TLDs) are required. It was the aim of the present work to ascertain if miniature LiF:Mg,Cu,P TLDs can effectively measure the dose distribution around 192Ir implants. 'Pin worm' TLDs (type MCP, diameter 0.6 mm, length 2 mm) were compared with GR-200R (SSDL, Beijing) rods cut in half. The TLDs were tested for reproducibility and energy dependence using high dose rate (HDR) and low dose rate (LDR) brachytherapy units. 192Ir measurements were performed in a tissue equivalent phantom accommodating hollow needles and catheters routinely used in brachytherapy. Pin worms had an average reproducibility of less than +/-2% (1 SD) and a detection limit of less than 10 microGy. The small dimensions of the pin worms allowed their placement within brachytherapy needles and catheters. The measured relative dose distribution was in good agreement with the predictions of a computerised treatment planning system (ADAC Pinnacle); however, limitations in the TLD energy correction did not allow for absolute dose comparison.

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine.

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

What is the prevalence of rheumatic disorders in general medical inpatients?

It has been suggested that rheumatological disorders are underdiagnosed in patients with medical problems and that this might be rectified by incorporating a standard brief screening examination as part of the routine assessment of all patients admitted to hospital with medical conditions. Therefore the GALS screening examination was used to assess the prevalence of rheumatic disease in 100 patients admitted with acute medical problems and in a further 100 in the rehabilitative phase of their disease. The nature of locomotor dysfunction in all patients with a positive result was defined by an independent review and then sensitivity and specificity of the screening test was calculated for rheumatic disease in both populations. The median age of the two populations were 63 and 78 years respectively, with more females in the rehabilitation group. The overall prevalence of a positive screening test was 53% in the acute and 94% in the chronic disease groups, although the false positive rate in the rehabilitation patients was 30% due to factors other than rheumatic disorders limiting locomotor function (mainly orthopaedic and neurological conditions). The diagnosis of a rheumatological disorder was made de novo in a significant minority (10%) of patients and was usually amenable to treatment. The commonest rheumatic disorder was osteoarthritis which accounted for 55% of all rheumatic disease, followed by inflammatory joint disease (16%), and osteoporosis (12%). In addition to osteoporosis, Paget's disease of bone and polymyalgia rheumatica were found more frequently in those patients undergoing rehabilitation than in those admitted with an acute medical problem. A number of clinically important associations between medical and rheumatic disorders were found, such as stroke disease with shoulder capsulitis and heart failure with gout. The sensitivity of the GALS screening test was extremely high (92% and 100%), while its specificity fell in the rehabilitation group from 83% to 17%. None the less, it is felt that this study indicates that the routine use of this test should be considered as part of the assessment of all hospitalised patients with medical problems, whether acute or chronic.

Payment levels, resource use, and insurance risk of medicaid versus private insured in three states.

Concerns with access and costs in the Medicaid program often lead policy makers to consider alternatives. These include subsidizing poor persons' purchases of health insurance in private markets or integrating Medicaid beneficiaries into commercial managed care systems. As policy makers consider such alternatives, a persistent question is, apart from the disabled within Medicaid, do younger Medicaid enrollees represent a different insurance risk than people of similar age and sex within private insurance pools? We use 1994 data from Georgia, Mississippi, and California to assess relative payment levels, resource use/costs, and risk-adjusted utilization of fee-for-service (FFS) Medicaid enrollees versus privately insured people. When resources are valued at private prices, the use by Medicaid enrollees represents a higher cost. After risk adjustment, Medicaid enrollee resource use appears higher than expected for the privately insured only for outpatient facility visits in the southern states and for inpatient days by pregnant women in California Medi-Cal. Indeed, we find evidence that Medicaid enrollees are underserved relative to their health needs. Given the higher dollar value of their resource usage, apparently obtained under FFS at discounted provider rates, and the lack of evidence on significant overuse relative to need, their integration into private provider systems appears challenging.

A biochemical hypothesis explaining the response of enhanced biological phosphorus removal biomass to organic substrates.

Anaerobic/aerobic batch experiments were conducted with a variety of volatile fatty (VFAs) and amino acids on two sequencing batch reactor populations displaying enhanced biological phosphorus removal. The batch experiments were consistent between the two systems and with the past literature: acetic and isovaleric acid were the most efficient substrates, and propionic acid was the least efficient of the 2-5 carbon VFAs (lack of acclimation was ruled out). A survey of the engineering and biochemical literature revealed that both acetic and isovaleric acid resulted in a negative reaction redox balance (i.e. it requires reducing equivalents such as NADH2) during their biotransformation to polyhydroxyalkanoates (PHAs). In addition, the survey indicated that acetic and isovaleric acid resulted in 3HB rather than 3HV or 3H2MV formation. Two possible hypotheses were put forward for evaluation: (1) it was hypothesized that a negative intracellular redox balance might result in higher PHA content since PHA biosynthesis could be sustained under anaerobic conditions (no NADH2 build up), and/or (2) it was hypothesized that 3HB resulted in greater P-uptake than other PHA forms such as 3HV.

A morphologic study of long-term retention of fluorocarbon after liquid ventilation.

STUDY OBJECTIVES: To determine how long perfluorinated hydrocarbons remain in the lung after they are used for lung ventilation in dogs, and to determine if residual perfluorinated hydrocarbons cause structural alteration or an inflammatory reaction of the lung. DESIGN: Adult dogs were anesthetized and received ventilation with oxygenated perfluorinated hydrocarbon liquid. Morphologic studies of tissue from the lungs of these dogs were performed at intervals of a few minutes to 10 years after reconversion to breathing gas. SETTING: University College of Medicine. PARTICIPANTS: Adult mongrel and beagle dogs. INTERVENTIONS: Anesthetized adult dogs breathed oxygenated liquid fluorocarbons for 1 h and then were reconverted to breathing air. Three fluorocarbons, FX-80 (C(8)F(16)O; 3M Company; St. Paul, MN), Caroxin-D (C(10)F(22)O(2); P-1D; Allied Chemical Company; Morristown, NJ), and Caroxin-F (C(9)F(20)O; P-12F; Allied Chemical Company), were used. Morphologic studies of the lungs of these animals were performed immediately after restoration of air breathing and at intervals for up to 10 years. Not all animals were studied at each time interval. MEASUREMENTS AND RESULTS: A transient, acute inflammatory reaction was followed by a massive influx of macrophages, which were at first intra-alveolar and later interstitial, especially around vessels and bronchioles. Fluorocarbons remained in the lung in diminishing amounts for at least 5 years, as evidenced by persistent vacuolated macrophages in the alveoli, interstitium, and hilar lymph nodes; fluorocarbon was also detected in these tissues by chemical assays. In no case was there fibrosis or any other structural alteration associated with the residual fluorocarbon, which suggests that it was inert. At 10 years, no evidence of residual fluorocarbon was seen morphologically.

Effect of asthma on the quality of life among children and their caregivers in the Atlanta Empowerment Zone.

BACKGROUND AND OBJECTIVE: Asthma is the most common chronic pediatric disease and exacts a toll on the health-related quality of life of affected children and their primary caregivers. This investigation describes the relationship between the clinical severity of asthma among inner-city children and their quality of life and that of their primary adult caregivers. METHODS: Telephone interview data were collected from individual adult caregivers of 5-12-year-old children with asthma. Questions addressed the history, diagnosis, and management of the child's asthma, the child's family and social background, the family's socioeconomic status, the caregiver's knowledge and attitude about asthma, and the health-related quality of life of both the child and the caregiver. An asthma severity score was calculated from the caregiver's responses to questions about their child's wheezing frequency, nocturnal and early morning symptoms, and speaking during an asthma attack, as well as the impact of the disease on their child's physical activity and breathing during the prior 4-month period. A clinical asthma triage score was determined from information collected at the emergency department about the child's oxygen saturation, alertness, use of accessory respiratory muscles, extent of breathlessness, and peak expiratory flow. Spearman correlation coefficients were used to identify association between quality of life and disease severity, caretaker's asthma knowledge, and functional impact of asthma symptoms. RESULTS: Data from 240 of 755 eligible children were analyzed. Most children were younger than 11 years, male, black, and non-Hispanic. The children's median duration of asthma diagnosis was 86% of their life (range less than 1 to 11.3 years, median 5.0 years). Of the primary caregivers, 69% had at least completed high school, and 90% reported a total monthly household income of $1,600 or less. The maximum possible quality-of-life score and the median for caregivers were 91 and 70, respectively; for children, the same scores were 69 and 58, respectively. In addition, there was significant negative correlation of the quality-of-life scores of both the caregivers and children with the number of schooldays the children missed (r = -0.24 and r = -0.26, respectively, P < .001 for both) and the caregivers' and children's asthma severity scores (r = -0.39 and r = -0.47, respectively, P < .001 for both). The quality-of-life scores of the children and caregivers did not correlate significantly with the asthma triage scores. CONCLUSIONS: The questionnaires captured baseline quality-of-life information about this urban population and will facilitate longitudinal monitoring. The fact that the quality-of-life scores of children with asthma correlated with those of their adult caregivers, but not with their clinical triage scores, highlights the impact of asthma on families and the importance of having a long-term comprehensive management plan that is not based on exacerbations, but that includes both the children and their primary caregivers.

The effect of longer-term creatine supplementation on elite swimming performance after an acute creatine loading.

We investigated the effect of an acute creatine loading (25 g per day for 4 days) and longer-term creatine supplementation (5 g of creatine or 5 g of placebo per day for 2 months) on the performance of 22 elite swimmers during maximal interval sessions. After the acute creatine loading, the mean of the average interval swim times for all swimmers (n = 22) improved (44.3+/-16.5 s before vs. 43.7+/-16.3 s after supplementation; P<0.01). Three of the 22 swimmers did not respond positively to supplementation. After 2 months of longer-term creatine supplementation or placebo, neither group showed a significant change in swimming performance (38.7+/-13.5 s before vs. 38.7+/-14.1 s after for the creatine group; 48.7+/-18.0 s before vs. 48.7+/-18.1 s after for the placebo group). We conclude that, in elite swimmers, 4 days of acute creatine loading improves swimming performance significantly when assessed by maximal interval sessions. However, longer-term supplementation for 2 months (5 g of creatine per day) did not benefit significantly the creatine group compared with the placebo group.

Positioning for partnerships. Assessing public health agency readiness.

BACKGROUND: Public health organizations are redefining their roles and aligning their structures with other components of the evolving American health system. Health departments must proactively and strategically plan how to position themselves for the coming years. Prior to implementing changes in functioning, structure, and/or future strategies, an organization should assess its internal readiness to commit to creating these substantial alterations. METHODS: Using a diagnostic tool developed by study investigators, employees of the Cobb and Douglas Counties Boards of Health were surveyed in order to assess their organizational readiness to enter into a strategic partnership with Promina Northwest, a not-for-profit hospital network in the Atlanta, Georgia area. Frequency distributions were conducted for each categorical variable and data were analyzed in aggregate and by job category. RESULTS: The 122 analyzed questionnaires revealed some significant trends. Respondents ranked the six factors having the greatest impact on an organization's ability to change in the following order: leadership, planning, teamwork, mission, information and operations. Interestingly, this rank ordering parallels the perceived strengths and weaknesses of the health departments as determined by the frequency of the most positive responses. CONCLUSION: Cobb and Douglas Counties Boards of Health have taken many key steps to prepare the organizations for significant proactive changes. Survey results emphasized the need for open channels of communication within the organizations and with the external environment so that effective planning can guide the strategic alignment of the health departments with community partners.

Assessment of D3 versus D2 receptor modulation of the discriminative stimulus effects of (+)-7-OH-DPAT in rats.

Although there are presently no highly selective agonists for the D3 dopamine receptor, a number of compounds reported to bind with moderate selectivity to D3 receptors are currently employed to investigate the importance of D3 receptors in the behavioral effects of psychostimulant drugs. For example, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) has been used extensively to investigate the role of D3 receptors in the reinforcing and discriminative stimulus properties of cocaine and d-amphetamine. However, recent investigations with a relatively selective D3 antagonist, PNU-99194A, have led us to question the importance of D3 receptors in the discriminative stimulus effects of 7-OH-DPAT. In the present study, 16 male Sprague-Dawley rats were trained to discriminate (+)-7-OH-DPAT (0.03 mg/kg, subcutaneously (s.c.)) from saline in a two-choice operant procedure using a fixed-ratio 20 schedule of water reinforcement. Consistent with previous findings, PNU-99194A appeared to attenuate only partially (+)-7-OH-DPAT discrimination at a dose that disrupted responding in most subjects. Moreover, a highly selective D2 agonist, PNU-91356A, substituted completely and in a dose-dependent manner for (+)-7-OH-DPAT, while d-amphetamine produced only partial substitution for the training drug. These data indicate that D2 receptor actions appear to be more important than D3 receptor actions in exerting the discriminative stimulus effects of (+)-7-OH-DPAT. Continued efforts to determine the relative importance of D2 vs D3 receptor actions in the modulation of the discriminative stimulus effects of (+)-7-OH-DPAT are discussed.