Blood platelets have long been recognised to bring about primary haemostasis with deficiencies in platelet production and function manifesting in bleeding while upregulated function favourises arterial thrombosis. Yet increasing evidence indicates that platelets fulfil a much wider role in health and disease. First, they store and release a wide range of biologically active substances including the panoply of growth factors, chemokines and cytokines released from a-granules. Membrane budding gives rise to microparticles (MPs), another active participant within the blood stream. Platelets are essential for the innate immune response and combat infection (viruses, bacteria, micro-organisms). They help maintain and modulate inflammation and are a major source of pro-inflammatory molecules (e.g. P-selectin, tissue factor, CD40L, metalloproteinases). As well as promoting coagulation, they are active in fibrinolysis; wound healing, angiogenesis and bone formation as well as in maternal tissue and foetal vascular remodelling. Activated platelets and MPs intervene in the propagation of major diseases. They are major players in atherosclerosis and related diseases, pathologies of the central nervous system (Alzheimers disease, multiple sclerosis), cancer and tumour growth. They participate in other tissue-related acquired pathologies such as skin diseases and allergy, rheumatoid arthritis, liver disease; while, paradoxically, autologous platelet-rich plasma and platelet releasate are being used as an aid to promote tissue repair and cellular growth. The above mentioned roles of platelets are now discussed.

Bacterial conjugation is an efficient and sophisticated mechanism of DNA transfer among bacteria. While mobilizable plasmids only encode a minimal MOB machinery that allows them to be transported by other plasmids, conjugative plasmids encode a complete set of transfer genes (MOB1T4SS). The only essential ingredient of the MOB machinery is the relaxase, the protein that initiates and terminates conjugative DNA processing. In this review we compared the sequences and properties of the relaxase proteins contained in gene sequence databases. Proteins were arranged in families and phylogenetic trees constructed from the family alignments. This allowed the classification of conjugative transfer systems in six MOB families:MOB(F), MOB(H), MOB(Q), MOB(C), MOB(P) and MOB(V). The main characteristics of each family were reviewed. The phylogenetic relationships of the coupling proteins were also analysed and resulted in phylogenies congruent to those of the cognate relaxases. We propose that the sequences of plasmid relaxases can be used for plasmid classification. We hope our effort will provide researchers with a useful tool for further mining and analysing the plasmid universe both experimentally and in silico.

A method for separating the outer and inner membranes of Pseudomonas aeruginosa PAO1 in the absence of added ethylenediaminetetraacetic acid was devised. The method yields two outer membrane fractions which show the same protein pattern on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but differ substantially in their relative contents of phospholipids. One of these outer membrane fractions and the inner membrane fraction are less than 4% cross-contaminated, as judged by the content of typical inner and outer membrane markers. The outer membrane contains four major protein bands with apparent molecular weights of 37,000, 35,000, 21,000 and 17,000. Vesicles reconstituted from lipopolysaccharide and phospholipids were impermeable to all saccharides included in the vesicles during vesicle formation. When the vesicles contained outer membrane proteins, they fully retained only those saccharides of greater than 9,000 molecular weight, suggesting that the exclusion limit of the outer membrane of P. aeruginosa for saccharides is substantially larger than the figure (500 to 600 daltons) obtained for certain enteric bacteria. The advantages and potential disadvantages of having an outer membrane with a higher exclusion limit for hydrophilic substances are discussed.

BACKGROUND

A program of home visitation by nurses has been shown to affect the rates of maternal welfare dependence, criminality, problems due to use of substances, and child abuse and neglect. However, the long-term effects of this program on children's antisocial behavior have not been examined.

OBJECTIVE

To examine the long-term effects of a program of prenatal and early childhood home visitation by nurses on children's antisocial behavior.

METHODS

Fifteen-year follow-up of a randomized trial. Interviews were conducted with the adolescents and their biological mothers or custodial parents.

METHODS

Semirural community in New York.

METHODS

Between April 1978 and September 1980, 500 consecutive pregnant women with no previous live births were recruited, and 400 were enrolled. A total of 315 adolescent offspring participated in a follow-up study when they were 15 years old; 280 (89%) were born to white mothers, 195 (62%) to unmarried mothers, 151 (48%) to mothers younger than 19 years, and 186 (59%) to mothers from households of low socioeconomic status at the time of registration during pregnancy.

METHODS

Families in the groups that received home visits had an average of 9 (range, 0-16) home visits during pregnancy and 23 (range, 0-59) home visits from birth through the child's second birthday. The control groups received standard prenatal and well-child care in a clinic.

METHODS

Children's self-reports of running away, arrests, convictions, being sentenced to youth corrections, initiation of sexual intercourse, number of sex partners, and use of illegal substances; school records of suspensions; teachers' reports of children's disruptive behavior in school; and parents' reports of the children's arrests and behavioral problems related to the children's use of alcohol and other drugs.

RESULTS

Adolescents born to women who received nurse visits during pregnancy and postnatally and who were unmarried and from households of low socioeconomic status (risk factors for antisocial behavior), in contrast with those in the comparison groups, reported fewer instances (incidence) of running away (0.24 vs 0.60; P = .003), fewer arrests (0.20 vs 0.45; P = .03), fewer convictions and violations of probation (0.09 vs 0.47; P<.001), fewer lifetime sex partners (0.92 vs 2.48; P= .003), fewer cigarettes smoked per day (1.50 vs 2.50; P= .10), and fewer days having consumed alcohol in the last 6 months (1.09 vs 2.49; P = .03). Parents of nurse-visited children reported that their children had fewer behavioral problems related to use of alcohol and other drugs (0.15 vs 0.34; P = .08). There were no program effects on other behavioral problems.

CONCLUSIONS

This program of prenatal and early childhood home visitation by nurses can reduce reported serious antisocial behavior and emergent use of substances on the part of adolescents born into high-risk families.

An improved method for allele replacement in Pseudomonas aeruginosa was developed. The two main ingredients of the method are: (i) novel ColE1-type cloning vectors derived from pBR322 and pUC19; and (ii) a family of cassettes containing a portable oriT, the sacB gene from Bacillus subtilis as a counter-selectable marker, and a chloramphenicol-resistance gene allowing positive selection of both oriT and sacB. Introduction of plasmid-borne DNA into the chromosome was achieved in several steps. The DNA to be exchanged was first cloned into the new ColE1-type vectors. After insertion of the oriT and sacB sequences, these plasmid were conjugally transferred into P. aeruginosa and plasmid integrants were selected. Plating on sucrose-containing medium allowed positive selection for both plasmid excision and curing since Pseudomonas aeruginosa strains containing the sacB gene in single- or multiple copy were highly sensitive to 5% sucrose in rich medium. This procedure was successfully used to introduce an agmR mutation into P. aeruginosa wild-type strain PAO1 and should allow the exchange of any DNA segment into any non-essential regions of the P. aeruginosa chromosome.

Two groups of mediators, the neuropeptides substance P and K and the monocyte-derived cytokines, interact in the neural regulation of immunological and inflammatory responses. Substance P, substance K, and the carboxyl-terminal peptide SP(4-11) induce the release of interleukin-1, tumor necrosis factor-alpha, and interleukin-6 from human blood monocytes. The neuropeptide effects occur at low doses, are specific as shown by inhibition studies with a substance P antagonist, and require de novo protein synthesis. Since monocyte-derived cytokines regulate multiple cellular functions in inflammation and immunity and since neuropeptides can be released from peripheral nerve endings into surrounding tissues, these findings identify a potent mechanism for nervous system regulation of host defense responses.

Neurotrophin-3-deficient (NT-3-deficient) mice were generated by gene targeting. Mutant mice displayed severe movement defects of the limbs, and most died shortly after birth. Substantial portions of peripheral sensory and sympathetic neurons were lost while motor neurons were not affected. Significantly, spinal proprioceptive afferents and their peripheral sense organs (muscle spindles and Golgi tendon organs) were completely absent in homozygous mutant mice. This correlated with a loss of parvalbumin and carbonic anhydrase-positive neurons in the dorsal root ganglion. No gross abnormalities were seen in Pacinian corpuscles, cutaneous afferents containing substance P and calcitonin gene-related peptide, and deep nerve fibers in the joint capsule and tendon. Importantly, the number of muscle spindles in heterozygous mutant mice was half of that in control mice, indicating that NT-3 is present at limiting concentrations in the embryo.

The peptide neurotransmitter substance P modulates sensitivity to pain by activating the neurokinin-1 (NK-1) receptor, which is expressed by discrete populations of neurons throughout the central nervous system. Substance P is synthesized by small-diameter sensory 'pain' fibres, and release of the peptide into the dorsal horn of the spinal cord following intense peripheral stimulation promotes central hyperexcitability and increased sensitivity to pain. However, despite the availability of specific NK-1 antagonists, the function of substance P in the perception of pain remains unclear. Here we investigate the effect of disrupting the gene encoding the NK-1 receptor in mice. We found that the mutant mice were healthy and fertile, but the characteristic amplification ('wind up') and intensity coding of nociceptive reflexes was absent. Although substance P did not mediate the signalling of acute pain or hyperalgesia, it was essential for the full development of stress-induced analgesia and for an aggressive response to territorial challenge, demonstrating that the peptide plays an unexpected role in the adaptive response to stress.

The discovery of C-reactive protein (CRP) half a century ago led to the description of the acute-phase reaction which is a fundamental response of the body to injury. Recent work on the structure and function of CRP has revealed the existence of a unique plasma protein family, including CRP and serum amyloid P component (SAP). These proteins have been conserved throughout vertebrate evolution. CRP binds specifically to a wide range of substances derived both from damaged autologous cells and from microorganisms. Complexed CRP can activate the complement system and, by virtue of its dramatically increased production in response to tissue injury, it probably acts primarily as a protective mechanism. However, in some circumstances CRP may also initiate or exacerbate inflammatory lesions. Clinical measurement of serum CRP is valuable as a screening test for organic disease and as a sensitive object index of disease activity and response to therapy in some inflammatory, infective, and ischaemic conditions. SAP closely resembles CRP in structure but not an acute-phase reactant in man. An apparently identical protein, amyloid P component (AP), is always found in amyloid deposits. AP is also found in normal tissues, as an integral constituent of vascular basement membranes and is located on the peripheral microfibrillar mantle of elastic fibres throughout the body.

Two vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid-lumbar spinal cord of the rat. The great majority (94-100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2-immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin- and enkephalin-containing boutons (including somatostatin-immunoreactive boutons that lacked calcitonin gene-related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present. We also investigated VGLUT expression in central terminals of primary afferents. Myelinated afferents were identified with cholera toxin B subunit; most of those in lamina I were VGLUT2-immunoreactive, whereas all those in deeper laminae were VGLUT1-immunoreactive, and some (in laminae III-VI) appeared to contain both transporters. However, peptidergic primary afferents that contained substance P or somatostatin (most of which are unmyelinated), as well as nonpeptidergic C fibres (identified with Bandeiraea simplicifolia isolectin B4) showed low levels of VGLUT2-immunoreactivity, or were not immunoreactive with either VGLUT antibody. As all primary afferents are thought to be glutamatergic, this raises the possibility that unmyelinated afferents, most of which are nociceptors, express a different vesicular glutamate transporter.

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.

OBJECTIVE

We examined whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading.

BACKGROUND

Endothelial dysfunction has been shown to occur in patients with diabetes mellitus (DM), and chronic hyperglycemia is implicated as a cause of endothelial dysfunction. However, in many patients with Type 2 DM and in those with impaired glucose tolerance (IGT), fasting blood glucose may be within normal limits, and hyperglycemia occurred only post-prandially.

METHODS

With ultrasound technique, we measured flow-mediated endothelium-dependent vasodilation during oral glucose tolerance test in 58 subjects: (17 patients with normal glucose tolerance [NGT], 24 with IGT, and 17 with type 2 DM). In addition, we measured the levels of thiobarbituric acid reactive substances (TBARS) and nitrite/nitrate.

RESULTS

Flow-mediated vasodilation decreased after glucose loading (NGT: 7.53+/-0.40, 4.24+/-0.28 and 6.35+/-0.40, in fasting, at 1- and 2-h, respectively, IGT: 6.50+/-0.48, 1.40+/-0.41** and 4.00+/-0.47*, respectively; DM: 4.77+/-0.37, 1.35+/-0.38** and 1.29+/-0.29%**, respectively; *p < 0.01 vs. fasting, **p < 0.005 vs. fasting). The TBARS concentration increased in parallel with plasma glucose level in each group (NGT: 1.43+/-0.07, 2.03+/-0.12 and 1.80+/-0.12, respectively; IGT: 1.65+/-0.11, 2.46+/-0.12** and 1.94+/-0.08*, respectively; DM: 1.73+/-0.07, 2.34+/-0.08** and 2.47+/-0.09** nmol/ml, respectively; *p < 0.05 vs. fasting, **p < 0.01 vs. fasting). Glucose loading did not change nitrite/nitrate concentration in any of the groups.

CONCLUSIONS

Hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis.

Exacerbated sensitivity to mechanical stimuli that are normally innocuous or mildly painful (mechanical allodynia and hyperalgesia) occurs during inflammation and underlies painful diseases. Proteases that are generated during inflammation and disease cleave protease-activated receptor 2 (PAR2) on afferent nerves to cause mechanical hyperalgesia in the skin and intestine by unknown mechanisms. We hypothesized that PAR2-mediated mechanical hyperalgesia requires sensitization of the ion channel transient receptor potential vanilloid 4 (TRPV4). Immunoreactive TRPV4 was coexpressed by rat dorsal root ganglia (DRG) neurons with PAR2, substance P (SP) and calcitonin gene-related peptide (CGRP), mediators of pain transmission. In PAR2-expressing cell lines that either naturally expressed TRPV4 (bronchial epithelial cells) or that were transfected to express TRPV4 (HEK cells), pretreatment with a PAR2 agonist enhanced Ca2+ and current responses to the TRPV4 agonists phorbol ester 4alpha-phorbol 12,13-didecanoate (4alphaPDD) and hypotonic solutions. PAR2-agonist similarly sensitized TRPV4 Ca2+ signals and currents in DRG neurons. Antagonists of phospholipase Cbeta and protein kinases A, C and D inhibited PAR2-induced sensitization of TRPV4 Ca2+ signals and currents. 4alphaPDD and hypotonic solutions stimulated SP and CGRP release from dorsal horn of rat spinal cord, and pretreatment with PAR2 agonist sensitized TRPV4-dependent peptide release. Intraplantar injection of PAR2 agonist caused mechanical hyperalgesia in mice and sensitized pain responses to the TRPV4 agonists 4alphaPDD and hypotonic solutions. Deletion of TRPV4 prevented PAR2 agonist-induced mechanical hyperalgesia and sensitization. This novel mechanism, by which PAR2 activates a second messenger to sensitize TRPV4-dependent release of nociceptive peptides and induce mechanical hyperalgesia, may underlie inflammatory hyperalgesia in diseases where proteases are activated and released.

The endothelium plays a pivotal role in modulating the reactivity of vascular smooth muscle through the formation of several vasoactive substances. We examined the effects of endothelium-dependent and independent vasodilators on forearm blood flow in 29 patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 21 control subjects, using venous occlusion plethysmography. Via a brachial artery cannula, increasing amounts of acetylcholine and glyceryl trinitrate were infused in doses of 60, 120, 180 and 240 mmol per min and 3, 6 and 9 nmol per min respectively. NG monomethyl-L-arginine, a stereospecific inhibitor of endothelium derived relaxing factor, was infused to inhibit basal and stimulated release of this dilator substance. Reactive hyperaemic forearm blood flow did not differ between groups. Forearm blood flow responses to each dose of acetylcholine were significantly greater in control than diabetic subjects (p less than 0.01 for all doses). NG monomethyl-L-arginine attenuated forearm blood flow from maximal stimulated values when responses were compared with the natural decline to acetylcholine in forearm flow in both control and diabetic subjects (p less than 0.05 for both groups), but had no effect on basal blood flow responses. Forearm blood flow responses to each dose of glyceryl trinitrate were significantly greater in control than diabetic subjects (p less than 0.05 for all). These data provide evidence for endothelial and smooth muscle dysfunction in diabetes which may have important therapeutic implications.

BACKGROUND

Disulfiram has emerged as a promising treatment for cocaine dependence, but it has not yet been evaluated in general populations of cocaine users.

OBJECTIVE

To compare the effectiveness of disulfiram therapy with that of a placebo condition in reducing cocaine use and to compare the effectiveness of 2 active behavioral therapies-cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT)-in reducing cocaine use.

METHODS

Randomized, placebo-controlled, double-masked (for medication condition), factorial (2 x 2) trial with 4 treatment conditions: disulfiram plus CBT, disulfiram plus IPT, placebo plus CBT, and placebo plus IPT.

METHODS

A community-based outpatient substance abuse treatment program.

METHODS

A total of 121 individuals meeting the criteria for current cocaine dependence.

METHODS

Patients received either disulfiram (250 mg/d) or placebo in identical capsules. Medication compliance was monitored using a riboflavin marker procedure. Both behavioral therapies (CBT and IPT) were manual guided and were delivered in individual sessions for 12 weeks.

METHODS

Random regression analyses of self-reported frequency of cocaine use and results of urine toxicology screens.

RESULTS

Participants assigned to disulfiram reduced their cocaine use significantly more than those assigned to placebo, and those assigned to CBT reduced their cocaine use significantly more than those assigned to IPT (P<.01 for both). Findings were consistent across all study samples (eg, intention to treat, treatment initiators, and treatment completers). Benefits of disulfiram use and CBT were most pronounced for participants who were not alcohol dependent at baseline or who fully abstained from drinking alcohol during treatment. Adverse effects experienced by participants who received disulfiram were mild and were not considerably different from those experienced by participants who received placebo.

CONCLUSIONS

Disulfiram and CBT are effective therapies for general populations of cocaine-dependent individuals. Disulfiram seems to exert a direct effect on cocaine use rather than through reducing concurrent alcohol use.

Cannabis use may increase the risk of psychotic disorders and result in a poor prognosis for those with an established vulnerability to psychosis. A 3-year follow-up (1997-1999) is reported of a general population of 4,045 psychosis-free persons and of 59 subjects in the Netherlands with a baseline diagnosis of psychotic disorder. Substance use was assessed at baseline, 1-year follow-up, and 3-year follow-up. Baseline cannabis use predicted the presence at follow-up of any level of psychotic symptoms (adjusted odds ratio (OR) = 2.76, 95% confidence interval (CI): 1.18, 6.47), as well as a severe level of psychotic symptoms (OR = 24.17, 95% CI: 5.44, 107.46), and clinician assessment of the need for care for psychotic symptoms (OR = 12.01, 95% CI: 2.24, 64.34). The effect of baseline cannabis use was stronger than the effect at 1-year and 3-year follow-up, and more than 50% of the psychosis diagnoses could be attributed to cannabis use. On the additive scale, the effect of cannabis use was much stronger in those with a baseline diagnosis of psychotic disorder (risk difference, 54.7%) than in those without (risk difference, 2.2%; p for interaction = 0.001). Results confirm previous suggestions that cannabis use increases the risk of both the incidence of psychosis in psychosis-free persons and a poor prognosis for those with an established vulnerability to psychotic disorder.

With the indirect immunofluorescence technique of Coons and collaborators the occurrence of substance P (SP)-like immunoreactivity was studied in spinal ganglia (L6-S1), the spinal cord (L6-S1) and the pad skin of the hind paw of the cat. In untreated cats a very dense network of SP-positive fibers was found in the spinal cord in Lissauer's fasciculus, in laminae I-III and a rather dense plexus was seen in the ventral horns, in the area around the central canal (laminae X) and in the medial parts of laminae VI and VII. SP-positive fibers were also observed in the connective tissue under the epithelium of the skin. However, in untreated cats no specific immunogluorescnece was observed in the spinal ganglia, dorsal roots or certain large peripheral nerve trunks. After certain experimental procedures such as local application of colchicine or compression of the dorsal root close to the spinal ganglion, SP-positive fluorescence was observed in a rather small number of neuronal cell bodies and in fibers. The fluorescent material was observed in the peripheral parts of the cytoplasm and the cell bodies were exclusively of the small type. Ten days after transection of the dorsal roots a marked decrease in the number of SP-positive fibers was observed in the substantia gelatinosa but not in the ventral horns. The present results give strong evidence for the occurrence of SP in a certain population of primary sensory neurons and support earlier findings that SP may act as a transmitter or modulator in these neurons.

The immune system and the nervous system maintain extensive communication, including 'hardwiring' of sympathetic and parasympathetic nerves to lymphoid organs. Neurotransmitters such as acetylcholine, norepinephrine, vasoactive intestinal peptide, substance P and histamine modulate immune activity. Neuroendocrine hormones such as corticotropin-releasing factor, leptin and alpha-melanocyte stimulating hormone regulate cytokine balance. The immune system modulates brain activity, including body temperature, sleep and feeding behavior. Molecules such as the major histocompatibility complex not only direct T cells to immunogenic molecules held in its cleft but also modulate development of neuronal connections. Neurobiologists and immunologists are exploring common ideas like the synapse to understand properties such as memory that are shared in these two systems.

A modified formalin test in mice was investigated. The pain response curve induced by 0.5% formalin was biphasic, having 2 peaks, from 0 to 5 min (first phase) and from 15 to 20 min (second phase). A low concentration of formalin was used, allowing the effects of weak analgesics to be detected. Centrally acting drugs such as narcotics inhibited both phases equally. Peripherally acting drugs such as aspirin, oxyphenbutazone, hydrocortisone and dexamethasone only inhibited the second phase. Aminopyrine and mefenamic acid which acted on both central and peripheral sites inhibited both phases, but the second phase was inhibited by lower doses. Thus, this method enables one to easily distinguish the site of action of analgesics. Furthermore, pain response in the first phase was inhibited by capsaicin-treated desensitization and Des-Arg9-(Leu8)-bradykinin (bradykinin inhibitor). The second phase was inhibited by compound 48/80 pretreatment, indomethacin and bradykinin inhibitor. Therefore, it is suggested that substance P and bradykinin participate in the manifestation of the first phase response, and histamine, serotonin, prostaglandin and bradykinin are involved in the second phase. These results indicate that the first and second phase responses induced by formalin have distinct characteristic properties, and it is a very useful method for examining pain, nociception and its modulation by pharmacological or other means.

To define the type of dietary fibre of fibre analogue with the greatest potential use in diabetic treatment, groups of four to six volunteers underwent 50-g glucose tolerance tests (GTT) with and without the addition of either guar, pectin, gum tragacanth, methylcellulose, wheat bran, or cholestyramine equivalent to 12 g fibre. The addition of each substance significantly reduced blood glucose concentration at one or more points during the GTT and generally reduced serum insulin concentrations. The greatest flattening of the glucose response was seen with guar, but this effect was abolished when hydrolysed non-viscous guar was used. The reduction in the mean peak rise in blood glucose concentration for each substance correlated positively with its viscosity (r = 0.926; P less than 0.01), as did delay in mouth-to-caecum transit time (r = 0.885; P less than 0.02). Viscous types of dietary fibre are therefore most likely to be therapeutically useful in modifying postprandial hyperglycaemia.

BACKGROUND

Little is known about the prevalence and characteristics of chronic pain among patients with different types of chemical dependency.

OBJECTIVE

To estimate the prevalence and to examine the characteristics of chronic severe pain in chemically dependent populations receiving methadone maintenance or inpatient residential treatment.

METHODS

Representative samples of 390 patients from 2 methadone maintenance treatment programs (MMTPs) and 531 patients from 13 short-term residential substance abuse treatment (inpatient) programs, all in New York State, were surveyed in late 2000 and early 2001.

METHODS

Prevalence of chronic severe pain, defined as pain that persisted for more than 6 months and was of moderate to severe intensity or that significantly interfered with daily activities.

RESULTS

Chronic severe pain was experienced by 37% of MMTP patients (95% confidence interval [CI], 32%-41%) and 24% of inpatients (95% CI, 20%-28%; P =.03). Pain of any type or duration during the past week was reported by 80% of MMTP patients and 78% of inpatients. Among those with chronic severe pain, 65% of MMTP patients and 48% of inpatients reported high levels of pain-related interference in physical and psychosocial functioning. Among MMTP patients, correlates of chronic pain in a multivariate model were age (odds ratio [OR], 2.08; 95% CI, 1.17-3.70), chronic illness (OR, 1.88; 95% CI, 1.07-3.29), lifetime psychiatric illness (OR, 1.77; 95% CI, 1.06-2.97), psychiatric distress (OR, 1.63; 95% CI, 1.22-2.18), and time in treatment (OR, 2.23; 95% CI, 1.06-4.68). Among inpatients, the correlates of chronic pain were race (blacks vs whites: OR, 0.52; 95% CI, 0.31-0.90; Hispanics vs whites: OR, 0.48; 95% CI, 0.24-0.95), drug craving (OR, 2.78; 95% CI, 1.54-5.02), chronic illness (OR, 2.17; 95% CI, 1.37-3.43), and psychiatric distress (OR, 1.36; 95% CI, 1.03-1.81). Among those with chronic severe pain, inpatients were significantly more likely than MMTP patients to have used illicit drugs, as well as alcohol, to treat their pain complaint (51% vs 34%, P =.005) but were less likely to have been prescribed pain medications (52% vs 67%, P =.01).

CONCLUSIONS

Chronic severe pain is prevalent among patients in substance abuse treatment, especially MMTP patients. Pain is associated with functional impairment and correlates of pain vary with the population. Self-medication for pain with psychoactive drugs appears especially problematic among substance users who enroll in drug-free treatment programs. Substance abuse treatment programs need to develop comprehensive and structured pain management programs.

OBJECTIVE

To present nationally representative data on 12-month and lifetime prevalence, correlates, and comorbidity of bipolar I disorder.

METHODS

The data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Prevalences and associations of bipolar I disorder with sociodemographic correlates and Axis I and II disorders were determined.

RESULTS

Prevalences of 12-month and lifetime DSM-IV bipolar I disorder were 2.0% (95% CI = 1.82 to 2.18) and 3.3% (95% CI = 2.76 to 3.84), respectively, and no sex differences were observed. The odds of bipolar I disorder were significantly greater among Native Americans, younger adults, and respondents who were widowed/separated/divorced and of lower socioeconomic status and significantly lower among Asians and Hispanics (p < .05). Men were significantly (p < .05) more likely to have unipolar mania and earlier onset and longer duration of manic episodes, while women were more likely to have mixed and major depressive episodes and to be treated for manic, mixed, and major depressive episodes. Bipolar I disorder was found to be highly and significantly related (p < .05) to substance use, anxiety, and personality disorders, but not to alcohol abuse.

CONCLUSIONS

Bipolar I disorder is more prevalent in the U.S. population than previously estimated, highlighting the underestimation of the economic costs associated with this illness. Associations between bipolar I disorder and Axis I and II disorders were all significant, underscoring the need for systematic assessment of comorbidity among bipolar I patients.