Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine under hair dye use conditions in p-phenylenediamine-allergic individuals.

BACKGROUND: The factors influencing elicitation responses in individuals allergic to p-phenylenediamine (PPD) in hair dyes are not well understood. OBJECTIVES: Investigation of the elicitation response to the new, less-sensitizing PPD alternative 2-methoxymethyl-p-phenylenediamine (ME-PPD) under simulated hair dye use conditions. METHODS: The cross-elicitation response to ME-PPD (2% in a hair dye test product for 30 min on forearm then rinsing) was analysed at days 2 and 3 in 30 PPD-allergic individuals with diagnostic patch test grades +, ++ or +++ according to the classification of the International Contact Dermatitis Research Group. RESULTS: Cross-reactivity to the ME-PPD-containing hair dye test product was elicited in nine of 30 subjects (30%), while 70% were negative. Cross-reactivity was elicited in two of four cases with grade +++, three of 10 with grade ++ and four of 16 with grade +. Under identical conditions, PPD was previously found to elicit a response in 21 of 27 PPD-allergic individuals. In 18 of these 21 individuals, either the strength of the cross-elicitation response to ME-PPD was decreased or no response occurred. CONCLUSIONS: Under simulated hair dye use conditions, a significantly lower degree of cross-elicitation to ME-PPD (30%) was observed than previously reported for PPD (32 of 38, 84%). Additionally, a decreased cross-elicitation strength was observed across all three patch test grades, likely reflecting the reduced skin-sensitization properties of ME-PPD. Consequently, careful dermatological evaluation is required to assess cross-reactivity to ME-PPD in patients allergic to hair dyes.

Psychopathology factors in first-episode affective and non-affective psychotic disorders.

BACKGROUND: Since the onset, prevalence, and course of specific psychopathological features rarely have been analyzed simultaneously from the start of dissimilar psychotic illnesses, we compared symptom-clusters in first-episode DSM-IV affective and non-affective psychotic disorders. METHODS: Subjects (N=377) from the McLean-Harvard First Episode Project hospitalized for first-lifetime primary psychotic illnesses were followed prospectively for 2 years to verify stable DSM-IV diagnoses. We ascertained initial symptoms from baseline SCID and clinical assessments, applying AMDP and Bonn psychopathology schemes systematically to describe a broad range of features. Final consensus diagnoses were based on intake and follow-up SCID assessments, family interviews, and medical records. Factor-analytic methods defined first-episode symptom-clusters (Factors), and multiple-regression modeling related identified factors to initial DSM-IV diagnoses and to later categories (affective, non-affective, or schizoaffective disorders). RESULTS: Psychopathological features were accommodated by four factors: I represented mania with psychosis; II a mixed depressive-agitated state; III an excited-hallucinatory-delusional state; IV a disorganized-catatonic-autistic state. Each factor was associated with characteristic prodromal symptoms. Factors I and III associated with DSM-IV mania, II with major depression or bipolar mixed-state, III negatively with delusional disorder, IV with major depression and negatively with mania. Factors I and II predicted later affective diagnoses; absence of Factor I features predicted non-affective diagnoses, and no Factor predicted later schizoaffective diagnoses. CONCLUSION: The findings contribute to descriptive categorizations of psychopathology from onset of dissimilar psychotic illnesses. This approach was effective in identifying and subtyping affective psychotic disorders early in their clinical evolution, but non-affective and schizoaffective conditions appear to be more complex and unstable.

Comorbid substance-use in schizophrenia: relation to positive and negative symptoms.

As substance use disorders (SUD) are common in schizophrenia patients, we tested the hypothesis that comorbid patients (SUD[+]) have more positive vs. negative symptoms than non-comorbid (SUD[-]) patients. From reports identified by literature-searching we compared Positive and Negative Syndrome Scale (PANSS) ratings in schizophrenia patients with and without SUD using meta-analytic methods. Among 9 comparisons (N=725 subjects), SUD[+] patients were more often men, and abused alcohol>cannabis>cocaine. SUD[+] patients had very significantly higher PANSS-positive, and lower PANSS-negative scores. Comorbid SUD in schizophrenia patients was associated with male sex and higher PANSS positive to lower negative scores. Cause-effect relationships remain to be clarified.

Use and effectiveness of intravenous heparin therapy for treatment of acute myocardial infarction in the elderly.

OBJECTIVES: We sought to determine the use and association with 30-day mortality of intravenous heparin for the treatment of acute myocardial infarction in elderly patients not treated with a reperfusion strategy and without contraindications to anticoagulation. BACKGROUND: The benefit of using full-dose intravenous heparin for the treatment of acute myocardial infarction in the elderly is not known. METHODS: We conducted a retrospective cohort study using hospital medical records of all Medicare beneficiaries admitted to the hospital with an acute myocardial infarction in Alabama, Connecticut, Iowa and Wisconsin from June 1992 through February 1993. RESULTS: Among the 6,935 patients > or = 65 years old who had no absolute chart-documented contraindications to heparin, 3,227 (47%) received early full-dose intravenous heparin therapy. After adjustment for baseline differences in demographic, clinical and treatment factors between patients with and without heparin, the use of heparin (odds ratio 1.02, 95% confidence interval 0.87 to 1.18) was not associated with a significantly better 30-day mortality rate. CONCLUSIONS: Although intravenous heparin was commonly used for treatment of acute myocardial infarction in the elderly, it was not associated with an improved 30-day mortality rate. Although the findings of this observational study must be interpreted with care, they lead us to question whether the prevalent use of intravenous heparin has therapeutic effectiveness in this population.

Readmission after hospitalization for congestive heart failure among Medicare beneficiaries.

BACKGROUND: Congestive heart failure is the most common discharge diagnosis for Medicare beneficiaries. While several single-center studies have suggested that these patients are particularly vulnerable to readmission, no recent study, to our knowledge, has reported the readmission rates for a large number of elderly patients with congestive heart failure across a diverse spectrum of hospitals. OBJECTIVES: To define the readmission rate for elderly patients discharged after an episode of congestive heart failure. To determine the spectrum of diagnoses that are responsible for readmissions among patients with congestive heart failure. To identify patient and hospital characteristics associated with a higher likelihood of readmission. METHODS: This observational study, using Medicare administrative files, evaluated readmission and death among all survivors of a hospitalization in Connecticut for congestive heart failure from fiscal year 1991 through fiscal year 1994. RESULTS: There were 17448 survivors of a hospitalization for congestive heart failure during the study period. In the 6 months following the index admission, 7596 patients (44%) were readmitted to a hospital at least once. Congestive heart failure was the most frequent reason for readmission among study patients, accounting for 18% of all readmissions. In the multivariable analysis, significant predictors of readmission included male sex (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.05-1.20), at least 1 prior admission within 6 months of the index admission (OR, 1.64; 95% CI, 1.53-1.77), Deyo comorbidity score of more than 1 (OR, 1.56; 95% CI, 1.45-1.68), and length of stay in the index hospitalization of more than 7 days (OR, 1.32; 95% CI, 1.24-1.41). While age was not a significant predictor of readmission, it became significant in a model with the combined outcome of readmission or death as the dependent variable. CONCLUSION: Readmission after a hospitalization for congestive heart failure is common among Medicare beneficiaries, with almost half of the patients readmitted within 6 months. This striking rate of readmission in a common diagnosis demands efforts to further clarify the determinants of readmission and develop strategies to prevent this adverse outcome.

The McLean-Harvard first-episode project: 6-month symptomatic and functional outcome in affective and nonaffective psychosis.

BACKGROUND: The McLean-Harvard First-Episode Project recruited affective and nonaffective patients at their first lifetime psychiatric hospitalization. METHODS: Baseline evaluation and 6-month follow-up in 257 cases yielded recovery outcomes defined by syndromal (absence of DSM-IV criteria for a current episode) and functional (vocational and residential status at least at baseline levels) status. Time to recovery was assessed by survival analysis, and risk factors by multivariate logistic regression. RESULTS: Syndromal recovery was attained by 77% of cases over an average of 84 days. By diagnostic group, syndromal recovery rates ranked (p = .001) major affective disorders (81%) > nonaffective acute psychoses (74%) > schizoaffective disorders (70%) > schizophrenia (36%). Functional recovery was significantly associated to syndromal recovery, diagnosis, shorter hospitalization normalized to year, and older age at onset. Average hospital stay declined across the study period, but recovery did not vary with year of entry. CONCLUSIONS: Syndromal recovery was achieved by nearly one half of patients within 3 months of a first lifetime hospitalization for a psychotic illness, but functional recovery was not achieved by 6 months in nearly two thirds of patients who had attained syndromal recovery.

Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy.

BACKGROUND: The frontal lobe has been implicated in the pathology of depression in adults. Through the use of magnetic resonance spectroscopy, altered brain choline levels have also been linked to the pathophysiology of affective disorders. METHODS: To identify possible alterations in orbitofrontal cortex levels of cytosolic choline in adolescents with and without depression, 22 depressed and 43 control adolescents were recruited. Of those recruited, usable proton magnetic resonance spectra were acquired from a voxel in the left anterior medial frontal lobe of 17 depressed (mean age 15.8+/-1.6) and 28 healthy adolescents (mean age 14.5+/-1.7). RESULTS: Orbitofrontal cytosolic choline/creatine (Cho/Cr) ratios (p =.032) and cytosolic choline/N-acetyl aspartate (Cho/NAA) ratios (p =.043) were significantly higher in the depressed subjects than in the control subjects. There were no significant differences between depressed and control subjects in gray or white matter content within the voxel. CONCLUSIONS: These findings suggest that brain cytosolic choline may be increased in depressed adolescents in comparison with control subjects and independent of a corresponding structural change. These results are consistent with similar, previously reported findings in adults and suggest that depression in adolescents is associated with alterations in orbitofrontal metabolism.

Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders.

OBJECTIVE: Effects of long-term lithium treatment for depressive and manic phases of type I and type II bipolar disorders were compared. METHOD: Clinical research records of 317 patients with DSM-IV-defined bipolar disorder (188 with type I and 129 with type II) were analyzed for frequency and duration of affective episodes and hospitalizations before (mean = 8.38 years) versus during (mean = 6.35 years) lithium maintenance treatment. Treatment effects were also assessed by survival analysis of interepisode intervals and by multivariate regression testing for factors associated with response to treatment. RESULTS: Bipolar I and bipolar II patients were ill before treatment a similar percentage of time, but the subtype distinction was supported descriptively. Lithium had superior benefits in type II patients, with significantly greater reduction of episodes per year and of the percentage of time ill. Reduction of depressive morbidity was similarly strong in both diagnostic types. During treatment, bipolar II patients had 5.9-fold longer interepisode intervals and were twice as likely as type I patients to have no new episodes. Starting lithium maintenance earlier predicted greater improvement. CONCLUSIONS: Lithium maintenance yielded striking long-term reductions of depressive as well as manic morbidity in both bipolar disorder subtypes, with greater overall benefits in type II patients and with earlier treatment.

Multinuclear magnetic resonance spectroscopy studies of brain purines in major depression.

OBJECTIVE: Studies of depressed adults have shown abnormalities in cerebral energy metabolism, as noted by low brain levels of nucleoside triphosphate (NTP), which primarily represents adenosine triphosphate (ATP). This study was undertaken to determine whether proton magnetic resonance spectroscopy (1H MRS) measures of the low-field purine resonance, which arises primarily from adenosine phosphates, can be used to assess abnormalities in cerebral purine metabolism in depressed adults. METHOD: Data from 1H MRS and phosphorus-31 (31P) MRS were acquired for depressed and nondepressed comparison subjects. Intensities of the purine resonance, by 1H MRS (7.5-8.5 ppm), and of NTP, by 31P MRS, were determined. RESULTS: Purine resonance intensities did not differ on average between depressed patients and comparison subjects. However, purine levels were approximately 30% lower in female depressed subjects who subsequently responded to fluoxetine treatment than in those who did not respond. Beta-NTP was lower by 21% in responders than in nonresponders and was correlated with purine levels for the depressed subjects. CONCLUSIONS: Brain purine levels are low in female depressed patients who respond to treatment with fluoxetine, suggesting that response to treatment might be predicted by using 1H MRS. These observations also suggest that agents that increase brain adenosine levels may have antidepressant efficacy.

Two-year syndromal and functional recovery in 219 cases of first-episode major affective disorder with psychotic features.

OBJECTIVE: Psychotic affective disorders are the most prevalent idiopathic psychoses, but their outcome from onset has rarely been studied. In this study, the authors determined the rate and latency of syndromal recovery and rates of functional recovery after first lifetime hospitalization in patients with first-episode psychotic affective disorders. METHOD: From first lifetime hospitalization in 1989-1996, 219 patients with a DSM-IV psychotic affective illness were assessed at intervals over 24 months. Time to syndromal recovery (no longer meeting DSM-IV episode criteria) was assessed by survival analysis, and functional recovery (regaining baseline vocational and residential status) was rated. Factors associated with recovery were identified by bivariate and multivariate methods. RESULTS: By 3, 6, 12, and 24 months after first hospitalization, syndromal recovery was attained by 65.1%, 83.7%, 91.1%, and 97.5%, respectively, of subjects. Time to syndromal recovery (6.1 weeks to 50% of subjects recovered) was shorter for patients who had bipolar disorder, were married, were age 30 or older at onset, lacked comorbidity, required relatively brief hospitalization, and received fewer medicines. Functional recovery by 6 (30.4%) and 24 months (37. 6% of patients) was 2.6-2.7 times less likely than syndromal recovery; 63.1% of those recovering syndromally did not recover functionally by 2 years. Functional recovery was associated with older age at onset and shorter hospitalization. Annual recovery rates remained stable as mean hospital length of stay decreased 3. 6-fold over the 8-year study period. CONCLUSIONS: Syndromal recovery was attained by most psychotic affective disorder patients soon after hospitalization, but only one-third recovered functionally by 24 months. The findings suggest that these very common psychotic illnesses can carry a grave functional prognosis from the initial episode and first hospitalization.

Determinants of appropriate use of angiotensin-converting enzyme inhibitors after acute myocardial infarction in persons > or = 65 years of age.

We sought to determine how often angiotensin-converting enzyme (ACE) inhibitors are prescribed as a discharge medication among eligible patients > or = 65 years old with an acute myocardial infarction; to identify patient characteristics associated with the decision to prescribe ACE inhibitors; and to determine the factors associated with the decision to obtain an evaluation of left ventricular function among patients who have no contraindications to ACE inhibitors. We addressed these aims with an observational study of consecutive elderly Medicare beneficiary survivors of an acute myocardial infarction hospitalized in Alabama, Connecticut, Iowa, and Wisconsin between June 1992 and February 1993. Among the 5,453 patients without a contraindication to ACE inhibitors at discharge, 3,528 (65%) had an evaluation of left ventricular function. Of the 1,228 patients without a contraindication to ACE inhibitors who had a left ventricular ejection fraction < or = 40%, 548 (45%) were prescribed the medication at discharge. In a multivariable analysis, an increased prescribed use of ACE inhibitors at discharge was correlated with several factors, including diabetes mellitus, congestive heart failure, ventricular tachycardia, and loop diuretics as a discharge medication. Patients admitted after the publication of the Survival and Ventricular Enlargement (SAVE) trial were significantly more likely to receive ACE inhibitors, although the absolute improvement in utilization was small in the 6 months after the trial results were published. In conclusion, improving the identification of appropriate patients for ACE inhibitors and increasing the prescription of ACE inhibitors for ideal patients may provide an excellent opportunity to improve care.

Psychostimulant augmentation during treatment with selective serotonin reuptake inhibitors in men with paraphilias and paraphilia-related disorders: a case series.

BACKGROUND: We describe an open trial of psychostimulants (primarily methylphenidate sustained release [SR]) added to selective serotonin reuptake inhibitors (SSRIs; primarily fluoxetine) during the course of pharmacologic treatment of men with paraphilias and paraphilia-related disorders (PRDs). METHOD: Twenty-six men with paraphilias (N = 14) or PRDs (N = 12) were assessed for life-time mood disorders and attention-deficit/hyperactivity disorder (ADHD) as defined by DSM-IV. All men were assessed at baseline for total sexual outlet and average time per day associated with paraphilia/PRD sexual behaviors. The indications for the addition of a psychostimulant to a stable dose of SSRI included the retrospective diagnosis of ADHD with persistent adult symptoms despite pharmacotherapy with an SSRI (N = 17); residual paraphilia/PRD fantasies, urges, and activities despite SSRI pharmacotherapy (N = 16); the persistence or presence of residual depressive symptoms despite SSRI pharmacotherapy (N = 6); relapse or loss of SSRI efficacy during the treatment of sexual impulsivity disorders (N = 4); and treatment of SSRI-induced side effects (N = 4). RESULTS: SSRI pharmacotherapy (mean +/- SD duration = 8.8+/-11.1 months) had statistically significant effects in diminishing paraphilia/PRD-related total sexual outlet (p < .001) and average time/day spent in paraphilia/PRD sexual behavior (p < .001). Addition of methylphenidate SR (mean dose = 40 mg/day; mean +/- SD duration = 9.6+/-8.2 months) was associated with additional statistically significant effects on paraphilia/PRD-related total sexual outlet (p = .003) and average time per day (p = .04) in addition to improvement of putative residual ADHD and depressive symptoms. CONCLUSION: Methylphenidate SR can be cautiously and effectively combined with SSRI antidepressants to ameliorate paraphilias and paraphilia-related disorders for the indications listed above.

Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders.

BACKGROUND: Whether mood-altering treatments reduce risk of suicidal behavior remains largely unproved. METHOD: We compared suicidal rates in published studies of patients treated with lithium with those who were not, and in a mood disorders clinic before, during, and after discontinuing lithium. RESULTS: Published reports indicate a 7.0-fold lower rate of suicidal acts with lithium treatment of manic-depressive patients. In new findings in over 300 bipolar patients, latency from illness onset to lithium maintenance averaged 8.3 years (from 11.0 years in women with bipolar II disorder to 6.9 years in men with bipolar I disorder), but half of all suicidal acts occurred in the first 7.5 of 18.3 years at risk. Most acts (89%) occurred during depressive (73%) or dysphoric-mixed (16%) mood states and were associated with previous severe depression, prior attempts, and lower age at onset. Morbidity was reduced 2.7-fold and suicidal acts per year 6.5-fold during lithium treatment, with 8.3-fold cumulative sparing of risk by 15 years on lithium. In the first year off lithium, affective illness recurred in 67% of patients, and suicidal rates rose 20-fold but were much lower thereafter; fatalities were 14 times more frequent after discontinuation of lithium. Early morbidity was 2.5-fold lower, and suicidal risk was 2.0-fold lower after slow versus rapid discontinuation. CONCLUSION: Lithium maintenance is associated with sustained reduction of suicidal acts in manic-depressive disorders. Treatment discontinuation, particularly abruptly, led to early affective morbidity and suicidal behavior. Improved diagnosis and treatment as well as earlier intervention for potentially lethal bipolar depression are urgently needed, as are studies of all mood-altering agents for effects on suicidal behavior.

Lithium treatment and risk of suicidal behavior in bipolar disorder patients.

BACKGROUND: Lithium may exert an antisuicidal effect in bipolar disorder patients, but this hypothesis requires further testing by direct comparison of patients with and without lithium treatment. METHOD: Risk of life-threatening suicidal acts over time and associated factors were analyzed in 310 patients with DSM-IV bipolar I (N = 186) or II (N = 124) disorder evaluated for a mean of 8.3 years before, and prospectively during, a mean of 6.4 years of lithium maintenance in a mood disorder clinic; 185 were also followed for a mean of 3.7 years after clinically discontinuing lithium. RESULTS: In 5233 patient-years of observation, 58 patients made 90 suicide attempts (8 were fatal). Survival analyses with Weibull modeling with adjustments for covariates indicated a highly significant 6.4-fold adjusted hazard ratio during versus before and 7.5-fold ratio after versus during lithium maintenance. Suicidal acts were more common early in the course of illness before lithium and were associated with prior suicide attempts, greater proportion of time depressed, and younger age. After the discontinuation of lithium, suicidal acts were more frequent in the first year than at later times or before start of lithium treatment. Fatalities were 9 times more frequent after versus during treatment. CONCLUSION: Lithium maintenance was associated with marked reduction of life-threatening suicidal acts, the number of which sharply increased after discontinuing lithium. Suicidal behavior was strongly associated with prior suicide attempts, more time depressed, and younger age or recent onset. Greater attention to suicidal risk in patients with bipolar depression and assessment of all proposed mood-stabilizing agents for antisuicidal effects are strongly encouraged.

Group therapy for patients with bipolar disorder and substance dependence: results of a pilot study.

BACKGROUND: The authors' goal was to pilot test a newly developed manual-based group psychotherapy, called Integrated Group Therapy (IGT), for patients with bipolar disorder and substance dependence. METHOD: In this open trial, patients with DSM-IV bipolar disorder and substance dependence (N = 45) were recruited in sequential blocks to receive either group therapy (N = 21) or 6 monthly assessments, but no experimental treatment (N = 24). RESULTS: When compared with patients who did not receive group therapy, patients who received IGT had significantly better outcomes on the Addiction Severity Index drug composite score (p < .03), percentage of months abstinent (p < .01), and likelihood of achieving 2 (p < .002) or 3 (p < .004) consecutive abstinent months. CONCLUSION: IGT is a promising treatment for patients with bipolar disorder and substance dependence, who have traditionally had poor outcomes. It is unclear, however, how much of the improvement among the group therapy patients is attributable to the specific content of the treatment. A study comparing this treatment with another active psychotherapy treatment is warranted.

Suicide attempts in major affective disorder patients with comorbid substance use disorders.

BACKGROUND: The widely accepted impression that substance abuse and dependence are associated with increased suicidal risk was evaluated by literature review and with new data. METHOD: Previous research on this association was reviewed, and clinical data on suicide attempts and substance use in 504 mood disorder patients hospitalized in 4 psychiatric units in Sardinia affiliated with the Italian mental health system were analyzed. RESULTS: The literature supports associations of alcohol and drug use comorbidity with major affective disorders, and of some substances (polyabuse, alcohol, heroin, cocaine, and even tobacco, but perhaps not marijuana or hallucinogens) with suicidal behavior. Our new findings generally supported these 2-way associations. Suicidal risks were similar in hospitalized men and women but were associated with bipolar II, bipolar I (mainly mixed), and unipolar depressive disorders as well as substance abuse, with little effect of type of agent. Substance abuse was more common in nonmixed bipolar disorders, men, and age below 30. CONCLUSION: The tendency for bipolar I, mainly nonmixed patients, to have a relatively high risk of substance abuse and low risk of suicide attempts indicates that mainly depressive or dysphoric (bipolar II, nonbipolar, and bipolar I, mainly mixed) mood disorders may be especially lethal. Differences in risks of substance abuse and suicidal behavior in men and in bipolar I patients further suggest that substance abuse and mood disorders may contribute to suicidal risk with at least partial independence or additivity.

Treating the suicidal patient with bipolar disorder. Reducing suicide risk with lithium.

Bipolar disorder is associated with increased mortality because of complications of commonly comorbid substance use and stress-sensitive medical disorders as well as accidents and very high rates of suicide. Long-term lithium treatment may be associated with reduced suicidal risk. We review and summarize findings that help to quantify relationships between the presence versus the absence of lithium maintenance and suicides or attempts in patients with bipolar or other major affective disorders. Results from 33 studies (1970-2000) yielded 13-fold lower rates of suicide and reported attempts during long-term lithium treatment than without it or after it was discontinued. Although greatly reduced, these rates remain above those estimated for the general population. Evidence for substantial, if incomplete, protection against suicide with lithium is supported by more compelling evidence than that for any other treatment provided for patients with mood disorders. Studies of commonly used, but incompletely evaluated, alternative treatments are required, and further protection against premature mortality can be anticipated with better protection against bipolar depression.

Illicit cocaine use patterns in intravenous-naive cocaine users following investigational intravenous cocaine administration.

This study evaluated whether cocaine use patterns changed following investigational intravenous cocaine administration to intravenous-naive cocaine users. Subjects were respondents to a follow-up survey who had participated in one to three intravenous double-blind cocaine (0.2 or 0.4 mg/kg) administration studies. The group included healthy men (n = 17) and women (n = 8) with histories of occasional cocaine use (lifetime self-reported use of 12+/-12 (mean +/- S.D.) exposures, primarily via nasal insufflation) who were recontacted an average of 39 weeks (range 7-107 weeks) after study participation. The recontacted group constituted 45% of the total eligible sample of 55 subjects. Baseline demographics for the recontacted and non-recontacted (n = 30) samples were similar, suggesting that the recontacted sample was representative of the group as a whole. Investigational cocaine exposure did not induce adverse health events in any subject. Self-reported cocaine use estimates obtained at follow-up were compared to baseline estimates obtained with identical questionnaires and were highly concordant (Spearman rank correlation p = 0.52 and 0.78, respectively; P < 0.02 and < 0.0002, respectively). This suggests that participants provided stable and reliable reports of cocaine use. No subject reported either illicit intravenous cocaine use or altered frequency of illicit cocaine use by the customary route after investigational intravenous cocaine exposure. These data suggest that illicit cocaine use frequencies and routes of administration are not altered following investigational intravenous cocaine administration to healthy, occasional cocaine users.

Effects of rapid cycling on response to lithium maintenance treatment in 360 bipolar I and II disorder patients.

INTRODUCTION: Rapid cycling (RC) in bipolar disorders is widely believed to predict future morbidity and poor treatment response, although empirical testing of its predictive utility remains limited. METHODS: In 360 DSM-IV bipolar I (N=218) and II (N=142) disorder subjects (64% women) followed over an average of 13.3 years, we evaluated factors associated with RC status with bivariate and multivariate techniques, and response to lithium maintenance treatment (recurrence rates, time ill, survival analysis of time to recurrence on lithium). RESULTS: RC risk (15.6% of cases) was 5. 1-times greater in bipolar II vs. I subjects (30.3%/6.0%), in minor excess in women vs. men (17.9%/11.5%), and associated with premorbid cyclothymia, depressive first episodes, older onset age, and being employed or married. Before lithium, RC vs. non-RC cases had more mean total (3.9/1.2), manic, and depressive episodes/year, and greater percent time ill (60%/38%). During treatment, prior RC status was unrelated to time to first recurrence and other measures of morbidity and improvement including percent time ill, although depressive episodes were 2.7-times more frequent, and there was 13.7% less chance of full protection from all recurrences in RC cases. LIMITATIONS: The study is naturalistic, without random assignment or blind assessment. CONCLUSIONS: The RC bipolar subtype was strongly associated with type II diagnosis, higher average prelithium episode frequency and percent time ill, and weakly with female sex, but not with greater overall morbidity during treatment.

Occlusion of the pig superior sagittal sinus, bridging and cortical veins: multistep evolution of sinus-vein thrombosis.

Cerebral sinus-vein thrombosis may lead to severe hemodynamic changes, elevated intracranial pressure (ICP), and brain edema. It is supposed that progression of the thrombus from the sinus into bridging and cortical veins plays a key role in the development of these pathophysiological changes, but this hypothesis lacks experimental proof. The aim of this study, using a novel animal model of sinus-vein thrombosis, was to evaluate the effects of a standardized occlusion of the superior sagittal sinus and its bridging and cortical veins on hemodynamic alterations, on brain water content, and on ICP in domestic pigs. In 10 animals, the middle third of the superior sagittal sinus was occluded with a catheter-guided balloon. Five of these pigs received an additional injection of 1 ml fibrin glue into the superior sagittal sinus anterior to the inflated balloon, leading to an obstruction of bridging and cortical veins. In five control animals the balloon was inserted but not inflated. Five pigs underwent cerebral angiography. Four hours after occlusion, the brains were frozen in liquid nitrogen, and coronal slices were examined for Evans blue dye extravasation, regional water content, and histological changes. Occlusion of the superior sagittal sinus alone did not affect ICP or cerebral perfusion pressure (CPP). The additional injection of fibrin glue caused an obstruction of cortical and bridging veins as well as severe increases in mean (+/- standard deviation) ICP to 49.4 +/- 14.3 mm Hg, compared with 8.3 +/- 4.5 mm Hg in sham-treated controls and 7.1 +/- 3.9 mm Hg in animals with occlusion of the superior sagittal sinus alone. There was also a steep fall in the mean CPP to 34.2 +/- 19.6 mm Hg compared with 96.4 +/- 13.8 mm Hg in the control group. White-matter water content anterior to the occlusion site was elevated to 81.9 +/- 3.7 gm/100 gm frozen weight in the fibrin group as compared to 70.7 +/- 2.2 gm/100 gm in controls. Posterior to the occlusion site, water content did not differ among the three groups. Angiography demonstrated collateral flow via cortical and bridging veins in animals with occlusion of the superior sagittal sinus alone. Additional fibrin glue obstructed these collateral vessels. The data suggest a multistep process of pathophysiological alterations in patients with sinus-vein thrombosis and may explain why these patients present with a wide variety of symptoms: minor neurological deficits or headache might indicate thrombosis of the superior sagittal sinus and/or its bridging veins.(ABSTRACT TRUNCATED AT 400 WORDS)