A description of a specialist led primary care based oral surgery service.

AIM: To describe the establishment of a referral only oral surgery service in a primary care setting together with the challenges, benefits and successes of the service. PROBLEM: In 1994 waiting times for hospital for oral surgery and maxillofacial procedures were unacceptably long. A proposal to establish a primary care oral surgery service aimed to complement the hospital-based service, reduce treatment delays. OUTCOME: Referrals commenced immediately in response to a managed launch with local dentists recognising the service as a source of expedient and convenient treatment for their patients. The service now treats up to 1300 patients per year. LEARNING POINTS: New dental services to dentistry can encompass different specialities. Initial capital investment is needed to develop a more cost-effective service. Recruitment of suitable specialist staff is a critical for success. Staffing, organisation and funding must be sustained.

Cooperation across the histocompatibility barrier: H2d T cells primed to antigen in an H-2d environment can cooperate with H-2k B cells.

H-2d spleen cells derived from either tetraparental or semiallogeneic radiation bone marrow chimeras can be primed to antigen within H-2d recipients to generate helper T cells capable of cooperating in a secondary response with equal efficiency with H-2d or H-2k B cells. Thus it would seem that the cooperative act between T and B cells does not require that the T cell interacts with its target B cells by either cell interaction genes or via an altered self mechanism involving both antigen and the target B-cell I-region products. This does not preclude a requirement for associative recognition or altered self in the interaction of helper T cells with accessory cells.

"Infectious" transplantation tolerance.

The maintenance of transplantation tolerance induced in adult mice after short-term treatment with nonlytic monoclonal antibodies to CD4 and CD8 was investigated. CD4+ T cells from tolerant mice disabled naïve lymphocytes so that they too could not reject the graft. The naïve lymphocytes that had been so disabled also became tolerant and, in turn, developed the capacity to specifically disable other naïve lymphocytes. This process of "infectious" tolerance explains why no further immunosuppression was needed to maintain long-term transplantation tolerance.

Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes.

BACKGROUND: We sought to expand on preliminary findings suggesting that anabolic-androgenic steroids produce psychiatric effects in some athletes who use them. METHODS: We compared 88 athletes who were using steroids with 68 nonusers, using the Structured Clinical Interview for DSM-III-R to diagnose psychiatric syndromes occurring in association with steroid use (if applicable) and in the absence of steroid use. Demographic, medical, and laboratory measures were also performed. RESULTS: Steroid users displayed more frequent gynecomastia, decreased mean testicular length, and higher cholesterol-high-density lipoprotein ratios than nonusers. Most strikingly, 23% of steroid users reported major mood syndromes--mania, hypomania, or major depression--in association with steroid use. Steroid users displayed mood disorders during steroid exposure significantly more frequently than in the absence of steroid exposure (P < .001) and significantly more frequently than nonusers (P < .01). Users rarely abused other drugs simultaneously with steroids. CONCLUSION: Major mood disturbances associated with anabolic-androgenic steroids may represent an important public health problem for athletes using steroids and sometimes for the victims of their irritability and aggression.

Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of 'schizophrenic' symptoms in the light of current research.

Present clinical and research methods of differential diagnosis of schizophrenia and affective psychoses rely very heavily on presenting symptoms and signs, especially in acute psychosis. We have reviewed studies bearing on this issue, including studies of the phenomenology of psychotic illness, outcome, family history, response to treatment with lithium carbonate, and cross-national and historical diagnostic comparisons. We conclude that most so-called schizophrenic symptoms, taken alone and in cross section, have remarkably little, if any, demonstrated validity in determining diagnosis, prognosis, or treatment response in psychosis. In the United States, particularly, overreliance on such symptoms alone results in overdiagnosis of schizophrenia and underdiagnosis of affective illnesses, particularly mania. This compromises both clinical treatment and research.

Drug use and life-style among college undergraduates. Nine years later.

A questionnaire study of drug use and life-style among college seniors, previously performed in 1969, was repeated at the same college in 1978 with identical methods. Moderate increases in marijuana use were found; cocaine use had increased dramatically; most other drug use changed only slightly. Differences between users and nonusers, already modest in 1969, had narrowed further by 1978: users and nonusers were indistinguishable on grades, athletics, other college activities, career plans, and subjective alienation. Only heterosexual activity and visits to a psychiatrist still distinguish users from nonusers.

Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial.

BACKGROUND: Field studies of illicit anabolic-androgenic steroid users suggest that some develop manic or aggressive reactions to these drugs-a potential public health problem. However, controlled laboratory evaluations of these effects remain limited. METHODS: In a randomized, placebo-controlled, crossover trial, we administered testosterone cypionate for 6 weeks in doses rising to 600 mg/wk and placebo for 6 weeks, separated by 6 weeks of no treatment, to 56 men aged 20 to 50 years. Psychiatric outcome measures included the Young Mania Rating Scale (YMRS), the Point Subtraction Aggression Paradigm (a computerized provocation test of aggression), the Aggression Questionnaire of Buss and Perry, the Symptom Checklist-90-R, daily diaries of manic and depressive symptoms, and similar weekly diaries completed by a "significant other" who knew the participant well. RESULTS: Testosterone treatment significantly increased manic scores on the YMRS (P = .002), manic scores on daily diaries (P = .003), visual analog ratings of liking the drug effect (P = .008), and aggressive responses on the Point Subtraction Aggression Paradigm (P = .03). Drug response was highly variable: of 50 participants who received 600 mg/wk of testosterone cypionate, 42 (84%) exhibited minimal psychiatric effects (maximum YMRS score, <10), 6 (12%) became mildly hypomanic (YMRS score, 10-19), and 2 (4%) became markedly hypomanic (YMRS score, > or =20). The 8 "responders" and 42 "nonresponders" did not differ significantly on baseline demographic, psychological, laboratory, or physiological measures. CONCLUSIONS: Testosterone administration, 600 mg/wk increased ratings of manic symptoms in normal men. This effect, however, was not uniform across individuals; most showed little psychological change, whereas a few developed prominent effects. The mechanism of these variable reactions remains unclear.

Valproate in the treatment of acute mania. A placebo-controlled study.

We conducted a placebo-controlled, double-blind study of valproate, a drug originally developed as an antiepileptic, in 36 patients with acute manic episodes who had previously failed to respond to or to tolerate lithium carbonate. Treatment duration was 7 to 21 days, with no other psychotropic medications permitted except lorazepam up to 4 mg/d during the first 10 days of treatment. Serum valproate concentrations were measured three times weekly; an unblinded investigator then adjusted dosage to produce serum concentrations between 50 and 100 mg/L. Valproate proved superior to placebo in alleviating manic symptoms. The 17 patients randomized to active drug demonstrated a median 54% decrease in scores on the Young Mania Rating Scale as compared with a median 5.0% decrease among the 19 patients receiving placebo. On the 100-point Global Assessment Scale of overall psychiatric functioning, patients receiving valproate improved by a median of 20 points as compared with a zero-point change with placebo. Significant differences also emerged on the Brief Psychiatric Rating Scale and in the number of supplemental doses of lorazepam required by the patients in each group. Substantial antimanic effects appeared within 1 to 4 days of achieving therapeutic serum valproate concentrations. Adverse effects were infrequent, with no adverse effect appearing significantly more frequently with valproate than with placebo. We conclude that valproate represents a useful new drug for the treatment of manic patients.

Risk factors for neuroleptic malignant syndrome. A case-control study.

A number of risk factors have been proposed for the development of neuroleptic malignant syndrome, but these have not been subjected to controlled study. To address this problem, we performed a case-control study comparing 18 patients with neuroleptic malignant syndrome and 36 matched neuroleptic-treated control patients with no known history of the syndrome to identify potential risk factors. Patients with neuroleptic malignant syndrome displayed significantly greater psychomotor agitation, received significantly higher doses of neuroleptics at greater rates of dosage increase, and received a greater number of intramuscular injections than controls.

The validity of DSM-III borderline personality disorder. A phenomenologic, family history, treatment response, and long-term follow-up study.

To test the validity of the DSM-III diagnosis of borderline personality disorder (BPD), we examined the phenomenology, family history, treatment response, and four-to-seven-year long-term outcome of a cohort of 33 patients meeting DSM-III criteria for BPD. We found that (1) BPD could be distinguished readily from DSM-III schizophrenia; (2) BPD did not appear to represent "borderline affective disorder," although many patients displayed BPD and major affective disorder concomitantly; and (3) BPD could not be distinguished on any of the indices from histrionic and antisocial personality disorders.

Neuropsychological performance in long-term cannabis users.

BACKGROUND: Although cannabis is the most widely used illicit drug in the United States, its long-term cognitive effects remain inadequately studied. METHODS: We recruited individuals aged 30 to 55 years in 3 groups: (1) 63 current heavy users who had smoked cannabis at least 5000 times in their lives and who were smoking daily at study entry; (2) 45 former heavy users who had also smoked at least 5000 times but fewer than 12 times in the last 3 months; and (3) 72 control subjects who had smoked no more than 50 times in their lives. Subjects underwent a 28-day washout from cannabis use, monitored by observed urine samples. On days 0, 1, 7, and 28, we administered a neuropsychological test battery to assess general intellectual function, abstraction ability, sustained attention, verbal fluency, and ability to learn and recall new verbal and visuospatial information. Test results were analyzed by repeated-measures regression analysis, adjusting for potentially confounding variables. RESULTS: At days 0, 1, and 7, current heavy users scored significantly below control subjects on recall of word lists, and this deficit was associated with users' urinary 11-nor-9-carboxy-Delta9-tetrahydrocannabinol concentrations at study entry. By day 28, however, there were virtually no significant differences among the groups on any of the test results, and no significant associations between cumulative lifetime cannabis use and test scores. CONCLUSION: Some cognitive deficits appear detectable at least 7 days after heavy cannabis use but appear reversible and related to recent cannabis exposure rather than irreversible and related to cumulative lifetime use.

The Structured Clinical Interview for DSM-III-R (SCID). II. Multisite test-retest reliability.

A test-retest reliability study of the Structured Clinical Interview for DSM-III-R was conducted on 592 subjects in four patient and two nonpatient sites in this country as well as one patient site in Germany. For most of the major categories, kappa s for current and lifetime diagnoses in the patient samples were above .60, with an overall weighted kappa of .61 for current and .68 for lifetime diagnoses. For the nonpatients, however, agreement was considerably lower, with a mean kappa of .37 for current and .51 for lifetime diagnoses. These values for the patient and nonpatient samples are roughly comparable to those obtained with other structured diagnostic instruments. Sources of diagnostic disagreement, such as inadequate training of interviewers, information variance, and low base rates for many disorders, are discussed.

A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group.

BACKGROUND: Long-term outcomes are often poor in patients with bipolar disorder despite treatment; more effective treatments are needed to reduce recurrences and morbidity. This study compared the efficacy of divalproex, lithium, and placebo as prophylactic therapy. METHODS: A randomized, double-blind, parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index manic episode (n = 372) were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were discontinued before randomization, except for open-label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatment. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive episode, average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania, and Global Assessment of Function scores. RESULTS: The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores. CONCLUSIONS: The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy. Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures.

Attributes of heavy vs. occasional marijuana smokers in a college population.

We sought to assess whether college students who smoked marijuana heavily were distinguishable from students who had used the drug only occasionally. We compared 45 long-term heavy marijuana smokers (individuals who had smoked daily for at least 2 years) with 44 "occasional" smokers (individuals who had never smoked more than 10 times in a month at any time in their lives), drawn from the student populations at two Boston-area colleges. measures included a questionnaire covering a range of demographic, drug use, and subjective items; the Rand Mental Health Inventory; and both the Axis I and Axis II sections of the Structured Clinical Interview for DSM-III-R. Heavy smokers reported higher rates of use of other substances, especially hallucinogens and cocaine, and they described greater subjective impairment of memory and motivation than occasional smokers; however, on a wide range of demographic, family background, and mental health measures, the heavy smokers proved almost indistinguishable from occasional smokers. Even the heaviest college marijuana smokers exhibit few demographic or psychiatric features that distinguish them from students who smoke only occasionally.

Porcine stress syndrome: an animal model for the neuroleptic malignant syndrome?

The porcine stress syndrome is a genetic disorder of swine which, like neuroleptic malignant syndrome, is characterized by hyperthermia, muscle rigidity, and autonomic dysfunction. We investigated the porcine stress syndrome as a possible animal model for neuroleptic malignant syndrome in two ways. First, we administered haloperidol and lithium carbonate, alone and in combination, to susceptible and resistant swine. Second, we attempted to prevent the syndrome by pretreating animals with bromocriptine. Porcine stress syndrome was induced in 2 of 3 susceptible and 1 of 3 resistant swine by combined treatment with lithium and haloperidol, but was not triggered by treatment with lithium or haloperidol alone. Pretreatment with bromocriptine conferred no protection against the syndrome.

Familial hyperkalemic periodic paralysis and bipolar disorder: a linkage and treatment study.

Familial hyperkalemic periodic paralysis and bipolar disorder are both hereditary disorders, characterized by episodes of illness separated by periods of remission, and possibly related to abnormalities in cellular ion transport. Recently we discovered a patient who suffered from both illnesses, as did his mother and grandmother. However, a detailed investigation of the pedigree suggested that these two disorders are not linked genetically. Furthermore, a placebo-controlled double-blind trial of lithium carbonate in this patient found lithium ineffective in preventing the attacks of paralysis, in contrast to another recent study which found lithium effective in hypermagnesemic periodic paralysis.

Sleep EEG in bulimia.

To evaluate the sleep electroencephalogram (EEG) characteristics of bulimia, all-night sleep EEGs were performed on 11 women meeting DSM-III criteria for bulimia. Comparison groups consisted of young women outpatients with major depression (n = 44) and young normal women (n = 20). The sleep EEGs of the bulimic patients were largely indistinguishable from those of the normal controls, except for a trend toward increased rapid eye movement (REM) density in the first REM period among the bulimic subjects. No differences in any sleep EEG measure were observed between bulimic patients with major depression and those without affective disorder. By contrast, the outpatients with major depression displayed marked sleep continuity disturbances, as well as significantly increased REM intensity and REM density, as compared to normal controls. Implications of these results with respect to the hypothesis that bulimia is related to major affective disorder are discussed.

Good sleep, bad sleep: a meta-analysis of polysomnographic measures in insomnia, depression, and narcolepsy.

Primary insomnia, major depression, and narcolepsy are usually considered to be separate disorders, distinguished by different polysomnographic profiles. But do polysomnographic data provide adequate evidence to segregate the three disorders, or might they display fundamentally the same sleep disturbance, differing only in degree? To test the viability of these two alternate hypotheses, the authors performed a meta-analysis of controlled polysomnographic studies of these disorders. A summary measure of degree of sleep disturbance was constructed from five variables: wakefulness after sleep onset, percentage of stage 1 sleep, percentage of stage 3 + 4 sleep, rapid eye movement (REM) latency, and REM density. The results of available studies for each variable were combined using a weighted average of effect sizes. An overall "sleep disturbance index" was then calculated by combining the estimates for the five above listed variables. On both the individual measures and especially on the summary index, insomnia, depression, and narcolepsy were arrayed on a simple continuum of progressively more severe sleep disturbance--congruent with the clinical observation that these disorders display progressively more disturbed sleep. These findings suggest that sleep can be disturbed in only a limited number of ways: in evaluating sleep architecture, it may not be possible to elaborate much beyond a single axis of good-to-bad sleep. Thus, polysomnographic measures may not provide adequate evidence to classify insomnia, depression, and narcolepsy as separate entities.

Progressive ventricular enlargement in schizophrenia: comparison to bipolar affective disorder and correlation with clinical course.

Previous studies of long-term serial changes in ventricular size in schizophrenia (SCZ) have yielded mixed, albeit predominantly negative results. The current study examined ventricular changes in CT scans over intervals of 1-to 4 1/2 years in chronic schizophrenic and bipolar patients. The results indicated significant progression of ventricular size from initial to final scan in the schizophrenia group but not in the bipolar or control groups; the percent increase in VBR over baseline was 25% (p less than 0.01) in the schizophrenia group as compared with 11% (n.s.) in the bipolar group. The increases in ventricular enlargement in the schizophrenic group did not correlate with duration of illness but did appear to show an irregular stepwise pattern in several patients. It is concluded that progressive ventricular enlargement after onset of illness does occur in a subgroup of schizophrenic patients characterized by a chronic or deteriorating clinical course. The etiological implications of this finding are discussed.

Assessing the subjective effects of stimulants in casual users. A methodology and preliminary results.

In order to assess the subjective effects of nefopam, a new non-opiate analgesic, a study was designed using highly educated, young, middle-to-upper class subjects in a naturalistic setting. Results suggest that the design is capable of differentiating variations in subjective drug effects. On a number of measures, 10 mg of d-amphetamine, a modest dosage, could be distinguished from placebo, showing changes in the direction expected for stimulant drugs. Nefopam (90 mg), on the other hand, showed few differences from placebo or caffeine (300 mg). Nefopam appeared mildly dysphoric, rather than stimulant, in subjective effects.