Pain activation of human supraspinal opioid pathways as demonstrated by [11C]-carfentanil and positron emission tomography (PET).

The role of the supraspinal endogenous opioid system in pain processing has been investigated in this study using positron emission tomography imaging of [11C]-carfentanil, a synthetic, highly specific mu opioid receptor (mu-OR) agonist. Eight healthy volunteers were studied during a baseline imaging session and during a session in which subjects experienced pain induced by applying capsaicin topically to the dorsal aspect of the left hand. A pain-related decrease in brain mu-OR binding was observed in the contralateral thalamus consistent with competitive binding between [11C]-carfentanil and acutely released endogenous opioid peptides. This decrease varied directly with ratings of pain intensity. These results suggest that the supraspinal mu-opioid system is activated by acute pain and thus may play a substantial role in pain processing and modulation in pain syndromes.

PET imaging of brain acetylcholinesterase using [11C]CP-126,998, a brain selective enzyme inhibitor.

PET and [(11)C]CP-126,998, an N-benzylpiperidinebenzisoxazole, were used to image brain acetylcholinesterase (AChE) distribution in healthy controls before and after administration of 5 mg donepezil p.o., a reversible AChE inhibitor. Logan plots were used to compute distribution volumes (V(T)). The V(T) of [(11)C]CP-126,998 was highest in the basal ganglia and cerebellum and lowest in the cerebral cortex, thalamus, amygdala, and hippocampus. The regional V(T) values correlated well with AChE concentration measured in vitro. Donepezil, given 4 h before PET scanning, induced a substantial inhibition of [(11)C]CP-126,998 binding (43-62%) in all brain regions when compared to the baseline PET study. The results of this study indicate that PET imaging of [(11)C]CP-126,998 may be useful in quantifying the distribution of regional brain AChE. This new PET radiotracer may potentially be employed in the diagnosis and treatment of patients with disorders of cholinergic neurotransmission, such as Alzheimer's disease.

Family planning clinic services in the United States: patterns and trends in the late 1990s.

CONTEXT: Publicly funded family planning clinics are a vital source of contraceptive and reproductive health care for millions of U.S. women. It is important periodically to assess the number and type of clinics and the number of contraceptive clients they serve. METHODS: Service data were requested for agencies and clinics providing publicly funded family planning services in the United States in 1997. The numbers of agencies, clinics and female contraceptive clients were tabulated according to various characteristics and were compared with similar data for 1994. Finally, county data were tabulated according to the presence of family planning clinics and private physicians likely to provide family planning care and according to the number of female contraceptive clients served compared with the number of women needing publicly funded care. RESULTS: In 1997, 3,117 agencies offered publicly funded contraceptive services at 7,206 clinic sites. Forty percent of clinics were run by health departments, 21% by community health centers, 13% by Planned Parenthood affiliates and 26% by hospitals or other agencies. Overall, 59% of clinics received Title X funding. Agencies operated an average of 2.3 clinics, and clinics served an average of 910 contraceptive clients per year. Altogether, clinics provided contraceptive services to 6.6 million women-approximately two of every five women estimated to need publicly funded contraceptive care. The total number of providers and the total number of women served remained stable between 1994 and 1997; at the local level, however, clinic turnover was high. Some 85% of all US counties had one or more publicly funded family planning clinics; 36% had one or more clinics, but no private obstetrician-gynecologist. CONCLUSIONS: Publicly funded family planning clinics are distributed widely throughout the United States and continue to provide contraceptive care to millions of US women. Clinics are sometimes the only source of specialized family planning care available to women in rural counties. However, the high rate of clinic tumover and the lack of significant growth in clinic numbers suggest that limited funding and rising costs have hindered the further expansion and outreach of the clinic network to new geographic areas and hard-to-reach populations.

Public or private providers? U.S. women's use of reproductive health services.

CONTEXT: U.S. women receive contraceptive and reproductive health services from a wide range of publicly funded and private providers. Information on trends in and on patterns of service use can help policymakers and program planners assess the adequacy of current services and plan for future improvements. METHODS: Women who reported in the 1995 National Survey of Family Growth that they had obtained any contraceptive or other reproductive health service in the past year were classified by their primary source of care, and the services they received, their characteristics and their primary source of care were analyzed. Logistic regression was used to test which factors predict women's use of publicly subsidized family planning clinics and of specific types of services. RESULTS: The percentage of women of reproductive age who obtained family planning services increased slightly between 1988 and 1995, primarily among women aged 30 and older. Nearly one in four women who received any contraceptive care visited a publicly funded family planning clinic, as did one in three who received contraceptive counseling or sexually transmitted disease (STD) testing and treatment. Women whose primary source of reproductive care was a publicly funded family planning clinic received a wider range of services than women who visited private providers; moreover, the former were significantly more likely to report obtaining contraceptive care or STD-related care, even after the effects of their background characteristics were controlled. Young, unmarried, minority, less-educated and poor women were more likely than others to depend on publicly subsidized family planning clinics. Source of health insurance was one of the most important predictors of the use of public family planning clinics: Medicaid recipients and uninsured women were 3-4 times as likely as women with private insurance to obtain clinic care. CONCLUSIONS: Publicly funded family planning clinics are an important source of contraceptive and other reproductive health care, providing millions of U.S. women with a wide range of services. Since women's need for reproductive care and for publicly subsidized care is not likely to diminish, clinics may be financially challenged in their efforts to continue delivering this broad package of services to growing numbers of uninsured or disenfranchised women.

Differences in teenage pregnancy rates among five developed countries: the roles of sexual activity and contraceptive use.

CONTEXT: Adolescent pregnancy, birth, abortion and sexually transmitted disease (STD) rates are much higher in the United States than in most other developed countries. METHODS: Government statistics or nationally representative survey data were supplemented with data collected by private organizations or for regional or local populations to conduct studies of adolescent births, abortions, sexual activity and contraceptive use in Canada, the United States, Sweden, France and Great Britain. RESULTS: Adolescent childbearing is more common in the United States (22% of women reported having had a child before age 20) than in Great Britain (15%), Canada (11%), France (6%) and Sweden (4%); differences are even greater for births to younger teenagers. A lower proportion of teenage pregnancies are resolved through abortion in the United States than in the other countries; however, because of their high pregnancy rate, U.S. teenagers have the highest abortion rate. The age of sexual debut varies little across countries, yet American teenagers are the most likely to have multiple partners. A greater proportion of U.S. women reported no contraceptive use at either first or recent intercourse (25% and 20%, respectively) than reported nonuse in France (11% and 12%, respectively), Great Britain (21% and 4%, respectively) and Sweden (22% and 7%, respectively). CONCLUSIONS: Data on contraceptive use are more important than data on sexual activity in explaining variation in levels of adolescent pregnancy and childbearing among the five developed countries; however, the higher level of multiple sexual partnership among American teenagers may help explain their higher STD rates.

Socioeconomic disadvantage and adolescent women's sexual and reproductive behavior: the case of five developed countries.

CONTEXT: Differences among developed countries in teenagers' patterns of sexual and reproductive behavior may partly reflect differences in the extent of disadvantage. However, to date, this potential contribution has received little attention. METHODS: Researchers in Canada, France, Great Britain, Sweden and the United States used the most current survey and other data to study adolescent sexual and reproductive behavior. Comparisons were made within and across countries to assess the relationships between these behaviors and factors that may indicate disadvantage. RESULTS: Adolescent childbearing is more likely among women with low levels of income and education than among their better-off peers. Levels of childbearing are also strongly related to race, ethnicity and immigrant status, but these differences vary across countries. Early sexual activity has little association with income, but young women who have little education are more likely to initiate intercourse during adolescence than those who are better educated. Contraceptive use at first intercourse differs substantially according to socioeconomic status in some countries but not in others. Within countries, current contraceptive use does not differ greatly according to economic status, but at each economic level, use is higher in Great Britain than in the United States. Regardless of their socioeconomic status, U.S. women are the most likely to give birth as adolescents. In addition, larger proportions of adolescents are disadvantaged in the United States than in other developed countries. CONCLUSIONS: Comparatively widespread disadvantage in the United States helps explain why U.S. teenagers have higher birthrates andpregnancy rates than those in other developed countries. Improving U.S. teenagers' sexual and reproductive behavior requires strategies to reduce the numbers of young people growing up in disadvantaged conditions and to help those who are disadvantaged overcome the obstacles they face.

Quantification of delta-opioid receptors in human brain with N1'-([11C]methyl) naltrindole and positron emission tomography.

The regional binding of N1'-([11C]methyl)naltrindole (MeNTI), a selective delta-opioid antagonist, was studied in healthy human subjects with positron emission tomography (PET). After the bolus intravenous administration of high specific activity [11C]MeNTI, PET was performed over 90 minutes. Arterial plasma samples were obtained during the scanning period and assayed for the presence of radiolabeled metabolites. The data were analyzed with various kinetic (two- and three-compartment models, Patlak graphical analysis) and nonkinetic (apparent volume of distribution and activity at a late scanning time) approaches. This tracer showed irreversible binding characteristics during the scanning period used. The results of the analyses also were compared with the density and distribution of delta-opioid receptors in the human brain in vitro. Additionally, computer simulations were performed to assess the effects of changes in receptor binding and tracer transport changes on the perceived binding parameters obtained with the models. A constrained three-compartment kinetic model was demonstrated to be superior to other quantification models for the description of MeNTI kinetics and quantification of delta receptor binding in the human brain with 11C-labeled MeNTI.

Gender and age influences on human brain mu-opioid receptor binding measured by PET.

OBJECTIVE: Both age and gender are being increasingly recognized as important factors influencing CNS structure and function. However, there are relatively few data on actual neurochemical differences between the sexes in human subjects or on their interaction with age. One of the central neurotransmitter systems for which sex differences have been suggested by animal models and clinical human data is the opioid. In this study the authors examined age- and gender-associated variations in mu-opioid receptor binding with positron emission tomography (PET). METHOD: Healthy human subjects were studied with PET and the radiotracer [11C]carfentanil, a selective mu-opioid agonist. Two separate subject groups were examined: one group of 24 men and 12 women was studied in a retrospective analysis of data, and a second group of 12 men and 18 women was recruited prospectively and studied with a higher-resolution scanner. RESULTS: Mu-opioid receptor binding potential (Bmax/Kd) was found to increase with age in neocortical areas and the putamen. Sex differences, with higher mu-opioid binding in women, were observed in a number of cortical and subcortical areas. Gender-by-age interactions were observed in the thalamus and the amygdala; in vivo mu-opioid binding declined in postmenopausal women to levels below those of men. CONCLUSIONS: These data imply that both age and gender are important variables to consider in the interpretation of investigations of human function in which the opioid system plays a role. Also, women's reproductive status (reproductive age versus postmenopausal) may influence the function of CNS opioid systems.

PET imaging of the dopamine transporter in progressive supranuclear palsy and Parkinson's disease.

OBJECTIVE: To differentiate the patterns of dopamine transporter loss between idiopathic PD and progressive supranuclear palsy (PSP). METHODS: We used the radiotracer [11C]-WIN 35,428 and PET. Regional striatal dopamine transporter binding was measured in the caudate, anterior putamen, and posterior putamen of six patients with L-dopa-responsive stage 2 PD, six patients with PSP, and six age-comparable healthy controls. RESULTS: In patients with idiopathic PD, the most marked abnormality was observed in the posterior putamen (77% reduction), whereas transporter density in the anterior putamen (60% reduction) and the caudate (44% reduction) was less affected. Unlike the patients with PD, the PSP group showed a relatively uniform degree of involvement in the caudate (40% reduction), anterior putamen (47% reduction), and posterior putamen (51% reduction). When posterior putamen/caudate ratios were calculated, these values were significantly lower in patients with PD than they were in patients with PSP (p = 0.0008) and the control group (p < 0.0001). CONCLUSIONS: Patients with PD have a more pronounced loss of dopamine transporters in the posterior putamen due to a subdivisional involvement of nigrostriatal dopaminergic projections in idiopathic PD. This technique is useful in the determination of neurochemical changes underlying PD and PSP, thus differentiating between them.

Tracers for imaging melanin with positron emission tomography.

The melanin binding properties of six radioligands were determined in vivo in the eyes of pigmented mice. Binding in the eyes of nonpigmented mice was used to assess nonmelanin binding characteristics. Of these radioligands, 3H-N-methylspiperone showed the best uptake and gave the best signal-to-noise ratio at all time points examined. Its binding appeared essentially irreversible. A PET study with 11C-N-methylspiperone was therefore carried out in a patient with a small ocular melanoma. Increased uptake of 11C-N-methylspiperone was observed in the melanoma. Our studies indicate that PET and radiolabeled NMSP might be used for imaging melanin and for the detection of pigmented melanoma. These results suggest that with a high resolution PET camera it may be feasible to image the melanin-containing cells (dopaminergic neurons) of the substantia nigra in the central nervous system, which could be of interest for the study of Parkinson's disease.

Women's interest in vaginal microbicides.

CONTEXT: Each year, an estimated 15 million new cases of sexually transmitted diseases (STDs), including HIV, occur in the United States. Women are not only at a disadvantage because of their biological and social susceptibility, but also because of the methods that are available for prevention. METHODS: A nationally representative sample of 1,000 women aged 18-44 in the continental United States who had had sex with a man in the last 12 months were interviewed by telephone. Analyses identified levels and predictors of women's worry about STDs and interest in vaginal microbicides, as well as their preferences regarding method characteristics. Numbers of potential U.S. microbicide users were estimated. RESULTS: An estimated 21.3 million U.S. women have some potential current interest in using a microbicidal product. Depending upon product specifications and cost, as many as 6.0 million women who are worried about getting an STD would be very interested in current use of a microbicide. These women are most likely to be unmarried and not cohabiting, of low income and less education, and black or Hispanic. They also are more likely to have visited a doctor for STD symptoms or to have reduced their sexual activity because of STDs, to have a partner who had had other partners in the past year, to have no steady partner or to have ever used condoms for STD prevention. CONCLUSIONS: A significant minority of women in the United States are worried about STDs and think they would use vaginal microbicides. The development, testing and marketing of such products should be expedited.

PIP: Research is underway to develop safe, effective microbicides that women can use vaginally to prevent sexually transmitted disease (STD) transmission. To estimate potential interest in microbicide use, interviews were conducted in 1998 with a nationally representative sample of 1000 sexually active US women 18-44 years of age. 20% of these women had either had an STD in the past or thought they might be infected. 93% of respondents indicated they would be interested in using a vaginal microbicide if they found themselves in a situation where they were at risk of STD transmission and 40% expressed current interest in such a product. Women who were not in a union were almost 3 times as likely as cohabiting women and 12 times as likely as married women to be both worried about contracting an STD and very interested in using a vaginal microbicide. Women who were 25-34 years of age, had a family income under US$20,000, did not have a college education, and were Black or Hispanic also were significantly more likely to express worry about their STD risk and interest in the product. The strongest independent predictor of whether a woman was worried about STDs and very interested in using a microbicide was whether she and her partner were already using condoms for STD prevention (odds ratio, 8.8). Two-thirds of respondents preferred a product that could be applied several hours before intercourse and was available without a prescription. 84% said they would use microbicide along with condoms rather than as a substitute for them. The findings of this survey suggest an estimated 12.6 million US women 15-44 years of age would be interested in current use of a microbicide. More than 7 million of these women would remain interested even if the product protected only against HIV, was just 70-80% effective, and cost $2 per application. Given this level of interest, the development, testing, and marketing of such products should be expedited.

Brain opioid receptor measurements by positron emission tomography in normal cycling women: relationship to luteinizing hormone pulsatility and gonadal steroid hormones.

The regulation of central mu-opioid receptors in women during the menstrual cycle was explored with positron emission tomography and the selective radiotracer [11C]carfentanil. Ten healthy women were studied twice, during their follicular and luteal phases. Plasma concentrations of estradiol, progesterone, testosterone, and beta-endorphin were determined immediately before scanning. LH pulsatility was measured over the 9 h preceding each of the two positron emission tomography scans. No significant differences in the binding potential of mu-opioid receptors (binding capacity/Kd) were observed between phases of the menstrual cycle. However, significant negative correlations were observed between circulating levels of estradiol during the follicular phase and mu-receptor binding measures in the amygdala and hypothalamus, two regions thought to be involved in the regulation of GnRH pulsatility. LH pulse amplitude was positively correlated with mu binding in the amygdala, whereas LH pulse number was negatively correlated with binding in this same region. No significant associations were noted between LH pulse measures and the hypothalamus for this sample. These results suggest that amygdalar mu-opioid receptors exert a modulatory effect on GnRH pulsatility, and that circulating levels of estradiol also regulate central mu-opioid function.

Mainstreaming contraceptive services in managed care--five states' experiences.

CONTEXT: The ongoing, rapid national transition from a health care financing and delivery system dominated by traditional indemnity insurance to one dominated by managed care has enormous implications for the accessibility of contraceptive services. METHODS: In each of five areas with relatively mature managed care environments (all of Colorado, Massachusetts and Michigan, as well as selected counties in California and Florida), all managed care organizations serving commercial or Medicaid enrollees were asked about their coverage of contraceptive services and the procedures for obtaining that care. In addition, all publicly funded family planning agencies in these areas were queried about their involvement with managed care plans, and representative samples of reproductive-age women at risk of unintended pregnancy and enrolled in managed care plans were asked about their plan's coverage and their experiences in obtaining contraceptive services. RESULTS: Fifteen percent of health maintenance organizations and point-of-service plans did not cover all five of the most commonly used medical contraceptive methods, and another 6% covered none of the methods. Only half the plans informed enrollees--and even fewer informed enrollees insured indirectly as dependents--of whether they covered contraceptive services. One in four women in commercial plans were unsure whether their plan covered oral contraceptives, and two in three did not know if their plan covered the other medical methods. Only one in four commercial plans have brought community-based family planning providers into their networks, and more than half of all publicly funded family planning agencies reported having no contracts with managed care organizations. Finally, nearly one in three women in managed care plans reported difficulties in obtaining contraceptive services, with 13% of enrollees in commercial plans waiting at least four weeks for an appointment for contraceptive care. CONCLUSIONS: To adequately address the contraceptive needs of their employees, employers must ensure that the health insurance plans they purchase provide adequate coverage of contraceptive methods. For their part, managed care organizations and state Medicaid programs should examine their policies and procedures to ensure that services are easily accessible to women needing contraceptive care.

Clinic provision of contraceptive services to managed care enrollees.

CONTEXT: Since the initiation of managed health care, little information has been available on whether family planning agencies are seeking ways to serve (and obtain reimbursement for serving) the growing number of clients who are managed care enrollees. METHODS: A 1995 mail survey sought information from a nationally representative sample of publicly funded family planning agencies about the agencies' involvement with managed health care plans and related clinic services, policies and practices. Completed surveys were received from 603 agencies, for an overall response rate of 68%. RESULTS: One-half of all publicly funded family planning agencies had served known enrollees or managed care plans. One-quarter (24%) had served managed care enrollees under contract, while others sought out-of-plan reimbursement for services provided to enrollees (13%) or used other sources to cover the cost of these services (12%). Family planning clinics administered by hospitals and community health centers were more likely than other types of clinics to have contracts to provide full primary-care services to managed care enrollees, whereas Planned Parenthood affiliates were more likely to have contracts that covered the provision of contraceptive care only. Clinics administered by health departments rarely had secured managed care contracts (10%), and only 36% reported even serving managed care enrollees. CONCLUSIONS: The challenges presented by managed care, and agencies' responses to these challenges, vary according to the type of organization providing contraceptive care. Family planning agencies need to seek relationships with managed care organizations based on those services that their clinics can best supply.

PIP: By the mid-1990s, 73% of insured private-sector employees in the US and 40% of Medicaid recipients were enrolled in a managed health care plan. To determine whether US family planning programs are serving managed care clients and receiving reimbursement, a survey was mailed in 1995 to a nationally representative sample of 885 publicly funded agencies. Completed surveys were returned by 603 agencies (68%). Half the agencies had served known enrollees of managed care plans; 24% had served managed care enrollees under contract, 13% had sought out-of-plan reimbursement for services provided to enrollees, and 12% had used other sources to cover the costs of these services. 47% of hospital-based family planning clinics, 43% of those affiliated with community health centers, 31% of Planned Parenthood affiliates, 20% of independent agencies, and 10% of health department agencies had at least one contract with a managed care plan. Family planning clinics administered by hospitals and community health centers were most likely to have contracts to provide full primary care services to managed care enrollees, while Planned Parenthood affiliates tended to have contracts that covered contraceptive provision only. In general, agencies reported that contracts with private plans placed more restrictions on enrollees (e.g., in terms of preauthorization, treatment plans, and use of specific laboratories and pharmacies) than contracts with Medicaid managed care plans. Confidentiality concerns and a desire to maintain long-standing clinical relationships were identified as the main reasons enrollees of managed care plans continued with out-of-plan providers. Overall, 49% of agencies surveyed expected further expansion of managed care to have a negative impact on their program. Family planning agencies must seek ways to continue to provide timely, confidential, and comprehensive contraceptive care as they work within or around the restrictions and requirements of managed care plans.

Autoradiographic and SPECT imaging of cerebral opioid receptors with an iodine-123 labeled analogue of diprenorphine.

The feasibility of imaging cerebral opioid receptors by single photon emission computed tomography (SPECT) has been established in baboon using a novel analog of diprenorphine (DPN) radiolabeled with iodine-123. The radioligand, [123I]-O-IA-DPN (C6-O-[123I]iodoallyl-DPN), was prepared in good yield (80%) with high radiochemical purity (>97%) and high specific radioactivity (>2,400 mCi/micromol). In ex vivo autoradiographic studies, with and without naltrexone blockade, [123I]-O-IA-DPN specifically labeled opioid receptors throughout the mouse brain. Nonmetabolized radioligand accounted for >90% of the signal observed in extracts of whole mouse brain. SPECT imaging trials showed that [123I]-O-IA-DPN selectively localized in regions of baboon brain known to have high densities of opioid receptors, such as striatum, thalamus, and temporal cortex. A much lower level of radioligand uptake and retention was noted for cerebellum, a region with few opioid binding sites. Pretreatment with naltrexone (6.5 pmol/kg) blocked [123I]-O-IA-DPN binding in all brain regions. Using naltrexone blockade to define the nonspecific component for a given region of interest, total to nonspecific binding ratios increased linearly (r > or = 0.98) over the SPECT study with maximal values for striatum (9.8), thalamus (7.1), and temporal cortex (6.9) reached at the last time point investigated (3.5 h). Specific binding for these regions, assessed as the difference between regional SPECT activity for the control and blocked states, proved irreversible over the observation period. By the end of the time course, specific [123I]-O-IA-DPN binding was >85% of total radioactivity in regions rich in opioid receptors and 62% of total radioactivity in cerebellum. The aggregate data are consistent with visualization of multiple opioid receptor types. Thus, [123I]-O-IA-DPN should prove useful for SPECT studies within the constraints imposed by a lack of innate selectivity for a single type of brain opioid receptor.

Tissue distribution and metabolism of the [32P]-labeled oligodeoxynucleoside methylphosphonate-neoglycopeptide conjugate, [YEE(ah-GalNAc)3]-SMCC-AET-pUmpT7, in the mouse.

Development of oligodeoxynucleotides (oligo-dNs) and their analogs as therapeutic agents is complicated by their low rate of transport across cellular membranes, which is required for interaction with the intracellular complementary nucleic acid sequences, and the lack of tissue-specific delivery. To overcome these obstacles, bioconjugates between cell surface receptor ligands and oligodeoxynucleoside methylphosphonates (oligo-MPs) have been constructed containing homogeneous, chemically defined covalent linkages. We have previously established that a model conjugate, [32P]-labeled [YEE(ah-GalNAc)3]-SMCC-AET-pUmpT7 (1), is delivered to Hep G2 cells in a ligand-specific manner, reaching a peak value of 26 pmol per 10(6) cells after 24 hours incubation at 37 degrees C (Hangeland et al., 1995). In this work, the in vivo behavior of this conjugate is explored. Administration of this conjugate to mice via tail vein injection demonstrates rapid uptake in liver to the extent of 69.9 +/- 9.9% of the injected dose after 15 minutes. Thereafter, the conjugate and its metabolites are rapidly cleared via the kidney and urine. Polyacrylamide gel electrophoresis analysis of extracts of Hep G2 cells and mouse liver reveal the conjugate 1 to be extensively metabolized. In contrast, the conjugate found in mouse urine is largely intact. These data show that this novel, biodegradable delivery vehicle represents a viable approach for the delivery of antisense oligo-MPs and other oligo-dN analogs to the liver for therapeutic and diagnostic applications.

Imaging of delta- and mu-opioid receptors in temporal lobe epilepsy by positron emission tomography.

The involvement of opioid neurotransmitter systems in seizure mechanisms is well documented. In previous positron emission tomography (PET) studies in patients with unilateral temporal lobe epilepsy, we have found evidence for differential regulation of the opioid-receptor subtypes. The present study extends our previous observations to delta-opioid receptors by using the delta-receptor-selective antagonist [11C]methylnaltrindole ([11C]MeNTI). Paired measurements of delta- and mu-opioid receptor binding and metabolic activity were performed with PET using [11C]MeNTI and [11C]carfentanil ([11C]CFN) and [18F]fluorodeoxyglucose ([18F]FDG), respectively. Binding of [11C]MeNTI and [11C]CFN increased and [18F]FDG uptake decreased in the temporal cortex (TC) ipsilateral to the focus. Decreases in [18F]FDG uptake were more widespread regionally than were increases in opioid receptors. Increases in the delta- and mu-receptor binding showed different regional patterns. Increases in mu-receptor binding were confined to the middle aspect of the inferior TC, whereas binding of delta receptors increased in the mid-inferior TC and anterior aspect of the middle and superior TC. The increase in delta receptors suggests their anticonvulsant action, as previously shown for the delta-receptor subtype, whereas the different regional pattern of receptor alterations suggest the distinct roles of different opioid-receptor subtypes in seizure phenomena.

The provision of public-sector services by family planning agencies in 1995.

Results from a 1995 survey of a nationally representative sample of 603 publicly funded family planning agencies reveal that 96% rely on federal funding, 60% on state funding and 40% on local funding to provide family planning and other services. Although only 25% of the contraceptive clients served by these publicly funded agencies--including health departments, hospitals, Planned Parenthood affiliates, independent agencies and community and migrant health centers--are Medicaid recipients, 57% have incomes below the federal poverty level and an additional 33% have incomes of 100-250% of the poverty level. Some 40% of the recipients of family planning services are black, Hispanic or from other minority groups, and 30% are younger than 20. Each agency employs an average of three physicians who together provide approximately seven hours of care per week and seven midlevel clinicians who provide 71 hours of care per week. The pill is the only contraceptive method provided by all agencies, but 96% provide the injectable; at least 90% spermicide, the condom and the diaphragm; 78% periodic abstinence; and 59% the implant. The remaining methods are provided by fewer than 50% of agencies. Almost 70% of agencies have at least one special program of outreach, education or services to meet the needs of teenagers, but far fewer have special programs for such hard-to-reach groups as the homeless, the disabled or substance users.

PIP: This article provides the findings from a 1995 nationally representative survey of 603 public-supported family planning (FP) service centers in the United States. 96% relied on federal funding, 60% relied on state funding, and 40% relied on local funding. 25% of clients were Medicaid recipients receiving narrowly targeted services. 57% had incomes below the federal poverty level, and an additional 33% had incomes of 100% to 250% of the poverty level. 30% were under 30 years old, and 50% were 20-29 years old. 61% were non-Hispanic Whites. The responses were weighted to reflect the actual distribution of family planning agencies according to type and Title X funding status. Agencies varied in the extent to which contraceptive services were the main focus. 80% of clients at Planned Parenthood affiliates and 65% of clients at independent FP clinics received contraceptive services. Only 45% of clients at hospital outpatient departments and 39% of clients at public health departments received family planning. Agencies receiving Title X funding received more poor contraceptive clients. The average delay between appointment scheduling and actual care was 4 days (Planned Parenthood clinic) or 11 days (hospital or health department clinic), and 9% of agencies provided same-day service. 32% averaged about 2 weeks. 97% offered evening appointments, and 73% offered weekend appointments. 71% followed-up missed appointments. An average of 3.1 physicians were employed to provide an average of 6.8 hours per week of care. An average of 6.7 mid-level nurses and clinicians provided 70.9 hours of patient care per week. This article includes findings on routine services, method mix, condoms, new methods, services for the hard-to-reach, services to teenagers, school-based clinics, noncontraceptive services, sources of funding, public funding, and fees charged. It is concluded that FP agencies will continue to need Title X funding even after Medicaid clients are switched to managed care alternatives.

Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving.

The endogenous opioid system has been recently implicated in the reinforcing actions of cocaine and other addictive drugs. In this study we examined mu opioid receptor binding in ten cocaine-dependent men and seven nonaddicted controls using positron emission tomography and [11C] carfentanil. Mu opioid binding was increased in several brain regions of the cocaine addicts studied 1-4 days after their last use of cocaine. Binding was positively correlated with the severity of cocaine craving experienced at the time. The upregulation of mu opioid receptor binding persisted after 4 weeks of monitored cocaine abstinence. These findings demonstrate for the first time the involvement of the endogenous opioid system in cocaine dependence and cocaine craving in living human subjects.