Analysis of traction-free assumption in high-resolution EBSD measurements.

The effects of using a traction-free (plane-stress) assumption to obtain the full distortion tensor from high-resolution EBSD measurements are analyzed. Equations are derived which bound the traction-free error arising from angular misorientation of the sample surface; the error in recovered distortion is shown to be quadratic with respect to that misorientation, and the maximum 'safe' angular misorientation is shown to be 2.7 degrees. The effects of localized stress fields on the traction-free assumption are then examined by a numerical case study, which uses the Boussinesq formalism to model stress fields near a free surface. Except in cases where localized stress field sources occur very close to sample points, the traction-free assumption appears to be admirably robust.

Depressive and anxiety symptoms and social support are independently associated with disease-specific quality of life in Colombian patients with rheumatoid arthritis.

OBJECTIVE: To examine the relationship between disease-specific Quality of Life (QOL) and socio-demographic, medical, and psychosocial factors in Colombian patients with Rheumatoid Arthritis (RA). METHODS: One hundred and three RA patients recruited from ambulatory centers in Neiva, Colombia were administered the Disease Activity Scale 28 (DAS-28), QOL-RA, Zung Self-Rating Depression Scale, State-Trait Anxiety Inventory (STAI), Interpersonal Support Evaluation List-12 (ISEL-12), and Symptom Checklist-90 Revised (SCL-90R). RESULTS: Lower QOL-RA was associated with lower socio-economic status (SES; r=0.26, p<0.01), higher likelihood of using opioids (t=-2.51, p<0.05), higher likelihood of comorbid pulmonary disease (t=-2.22, p<0.05), and lower ISEL-12 sub-scales (r's=0.41-0.31, p's<0.001). Lower QOL-RA was associated with higher DAS-28 (r=-0.28, p<0.01), Visual Analog Scale (VAS; r=-0.35, p<0.001), Zung Depression (r=-0.72, p <0.001), STAI-State (r=-0.66, p<0.001), STAI-Trait (r=-0.70, p<0.001), SCL-90R Global Severity Index (r=-0.50, p<0.001), SCL-90R Positive Symptom Total (r=-0.57, p<0.001), and all SCL-90R sub-scales (r's=-0.54--0.21, p's<0.01). A multivariate linear regression model indicated that SES (B=2.77, p<0.05), Zung Depression (B=-0.53, p<0.001), STAI-State (B=-0.26, p<0.05), and ISEL-12 Belonging (B=1.15, p<0.01) were independently associated with QOL-RA, controlling for significant associations. CONCLUSIONS: More depressive and anxiety symptoms were independently associated with lower disease-specific QOL, while higher perceptions of having people to do activities with (belonging social support) and higher SES were independently associated with higher disease-specific QOL. Psychosocial factors impact QOL in RA above and beyond disease activity. Additional research into the benefits of psychosocial assessment of RA patients and provision of comprehensive care to improve QOL is warranted.

Core body temperature in patients with seasonal affective disorder and normal controls in summer and winter.

The rationale for phototherapy in seasonal affective disorder (SAD) was originally based on the notion that SAD patients were light deprived during the wintertime and needed more light. We previously found normal temperature profiles of untreated SAD patients during the winter, and that phototherapy significantly enhanced the amplitude of the circadian temperature profile in SAD patients during the winter (Rosenthal et al 1990). We hypothesized that summer would act similarly on the temperature rhythm of these patients. In this study we examined the temperature data from SAD patients and normal controls during the summer and compared it to the results of our previous study. We found identical profiles for SAD patients and normal controls during the summer and that summer significantly lowered the overall temperature profiles of both groups and did not alter the amplitudes. These results raise questions about the validity of the current theories of the mechanism of light therapy.

Platelet [3H]paroxetine binding, 5-HT-stimulated Ca2+ response, and 5-HT content in winter seasonal affective disorder.

The present study was designed to evaluate cellular serotonergic functions in winter seasonal affective disorder (SAD) using serotonin (5-HT)-stimulated Ca2+ response as an integrated measure of 5-HT2 receptor function in platelets, [3H]paroxetine binding to characterize the platelet 5-HT transporter and 5-HT content as an index of the platelet storage capacity for this neurotransmitter amine. Purified density-dependent subpopulations of platelets in untreated and light-treated SAD patients and matched controls were investigated in order to control for possible variations in platelet turnover. We found no differences between SAD patients and controls on any of the measures, nor between light therapy conditions in SAD patients, although we found a higher Bmax of [3H]paroxetine binding and 5-HT content in heavy platelets compared to light platelets. Although the validity of platelet serotonergic measures as a model for brain serotonergic systems still remains to be elucidated, we found no evidence of platelet serotonergic abnormalities in our sample of SAD patients.

Effects of light treatment on core body temperature in seasonal affective disorder.

Abnormalities in circadian rhythms of core body temperature have been reported previously in depressed patients. In this study, we compared the temperature rhythms of 10 depressed seasonal affective disorder (SAD) patients with winter depression with those of 12 normal controls and evaluated the effects of bright light on temperature in SAD. Unlike previous studies of depressed patients, the temperature curves of the patients and normal controls during the off-light condition were nearly identical. We found a significant difference in amplitude between the patients in the untreated and light-treated conditions. Although there was no systematic difference in circadian phase across groups or treatment conditions, we present preliminary evidence that suggests that phase-typed subgroups may be present in the population distinguished by their treatment responses.

Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder.

OBJECTIVE: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. METHOD: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. RESULTS: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. CONCLUSIONS: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.

The use of vasopressin in the treatment of upper gastrointestinal haemorrhage.

Vasopressin is a potent vasoconstrictor which greatly reduces mesenteric blood flow. In patients with portal hypertension this results in decreased portal venous flow and portal pressure. Because of this property, vasopressin has been used for years in the therapy of variceal haemorrhage. A few controlled trials show that vasopressin causes a decrease in bleeding but has no effect on survival. It has been shown that intravenous vasopressin is just as effective as intra-arterial, and is associated with fewer complications. The inability to influence the outcome of variceal haemorrhage significantly may be related to suboptimal dosing due to the occurrence of systemic complications at higher doses. The combination of vasopressin with either sodium nitroprusside or nitroglycerin (glyceryl trinitrate) has resulted in a further decline of portal pressure, along with amelioration of most of the adverse haemodynamic effects of vasopressin. Whether or not clinical efficacy is increased when vasopressin is combined with sodium nitroprusside or nitroglycerin remains to be proven. Analogues of vasopressin, such as terlipressin, held early promise as agents which would be as effective as vasopressin, without the cardiac adverse effects. Recent data have not supported this and at present there is little to suggest any advantage of terlipressin over vasopressin. Virtually no adequate studies have yet been performed to support the use of vasopressin in the treatment of non-variceal haemorrhages. There is reason to suspect that vasopressin can effectively control bleeding from haemorrhagic gastritis, but the subsequent results of inducing gastric ischaemia in an already damaged gastric mucosa are unknown. In summary, vasopressin appears to have little effect on the mortality of patients with variceal haemorrhage. It may, however, help control the haemorrhage in some patients by lowering the portal pressure. Cardiovascular complications limit the dose that can be used but it is hoped that by combining vasopressin with nitroglycerin, a more effective and safe therapy will be available for variceal haemorrhages.

Trends in antifungal research.

With the increasing use of aggressive immunosuppressive therapies in the management of a variety of patient populations, the continuing presence of the AIDS pandemic and the therapeutic advances employed in critical care settings, an increasing number of serious fungal infections are being encountered by today's practicing clinicians. Traditionally, antifungal drug therapy has been delivered by means of intravenous infusion, oral administration, or topical application. Recently, a number of alternative routes of antifungal drug delivery have been developed and investigated, and the traditional means of antifungal administration have been improved to facilitate the therapeutic use of new and reformulated antifungal agents. Organized based on the route of administration, this chapter reviews these advances in antifungal drug delivery.

Remembering with and without awareness in a depressed mood: evidence of deficits in initiative.

We propose that depressive deficits in remembering are revealed in tasks that allow the spontaneous use of strategies; tasks that bypass or direct the use of strategies should not produce depressive deficits. College students received depressive- or neutral-mood inductions after answering questions worded to reflect homophones' less common meaning. After the inductions, subjects spelled old and new homophones and showed no effect of the depressive inductions on unaware memory for the old homophones. Subsequent tests of recognition did, however, reveal differences according to the induced mood or the presence of naturally occurring depression (in Experiment 3). The differences, evidence of nondepressed subjects' use of strategies, tended to disappear when all subjects were provided with strategies for spelling or recognition. The results indicate that depressives experience deficits in cognitive initiative. We review the literature on depressive memory from this perspective.

Association of antibiotic utilization measures and control of multiple-drug resistance in Klebsiella pneumoniae.

OBJECTIVE: To study the association of antibiotic-utilization measures and control of multidrug-resistant (MDR) Klebsiella pneumoniae after emergence in two hospitals in our medical center. DESIGN AND SETTING: Rates of MDR K. pneumoniae at two hospitals were compared before and after acute interventions, including emphasis on Contact Precautions and education in antibiotic utilization. Antipseudomonal beta-lactam antibiotic use was measured before and after the interventions at both hospitals. Pulsed-field gel electrophoresis of whole cell DNA was used as a marker of strain identity. RESULTS: Clonal strain dissemination was the major mechanism of emergence at hospital A; emergence was polyclonal at hospital B. Antibiotic-utilization interventions at both institutions included physician education regarding the association of ceftazidime use and MDR K. pneumoniae. At hospital A, ceftazidime use decreased from 4,301 g in the preintervention period, to 1,248 g in the postintervention period. Piperacillin-tazobactam use increased from 12,455 g to 17,464 g. Ceftazidime resistance in K. pneumoniae decreased from 110 (22%) of 503 isolates to 61 (15%) of 407 isolates (P<.05); piperacillin-tazobactam resistance decreased from 181 (36%) of 503 to 77 (19%) of 407 isolates (P<.05). At hospital B, ceftazidime use decreased from 6,533 g in the preintervention period to 4,792 g in the postintervention period. Piperacillin-tazobactam use increased from 58,691 g to 67,027 g. Ceftazidime resistance in K. pneumoniae decreased from 42 (10%) of 415 isolates to 19 (5%) of 383 isolates (P<.05). Piperacillin-tazobactam resistance decreased from 91 (22%) of 415 isolates to 54 (14%) of 383 isolates (P<.05). Follow-up data showed continued decrease in piperacillin-tazobactam resistance despite increased use at both hospitals. CONCLUSIONS: Antibiotic-use measures may be particularly important for control of MDR K. pneumoniae, whether emergence is clonal or polyclonal.

Pharmacodynamics of fluconazole, itraconazole, and amphotericin B against Candida albicans.

The objective of this study was to evaluate the pharmacodynamic activity of fluconazole, itraconazole, and amphotericin B against Candida albicans. Susceptibilities were determined according to the NCCLS guidelines (M27). Time-kill studies were performed using antifungal concentrations of 0.25-32 x MIC. Samples were withdrawn at predetermined timepoints, then plated using a spiral plater. Colony counts were determined after incubation at 35 degrees C for 24 h. The AUKC(0-48) was plotted against the concentration/MIC ratio. Candida isolates (95-2672, 96-15, and 95-2542) were classified as susceptible, susceptible-dose dependent, and resistant to fluconazole and itraconazole (MIC = 0.25 and 0.03 microg/mL, 32 and 0.5 microg/mL, 64 and 1 microg/mL; respectively). All three isolates were susceptible to amphotericin B (MIC = 0.13 microg/mL). Fluconazole inhibited the growth of the susceptible and S-DD isolates and was ineffective at all concentrations against the resistant isolate. Itraconazole, on the other hand, inhibited growth of the susceptible isolate, but was ineffective for the S-DD and resistant isolates. Maximal effectiveness was noted at the concentration 8 x MIC and 2 x MIC for fluconazole and itraconazole, respectively. Amphotericin B demonstrated concentration-dependent antifungal activity. The times necessary for the colony counts to fall below the limit of quantification were inversely related to increasing concentrations of amphotericin B. The maximal effect for amphotericin B was recorded at 2 x MIC. In summary, the triazoles inhibit growth of susceptible C. albicans; however, careful consideration should be given to the MIC for S-DD isolates because itraconazole may not be active if the MIC is reported in the higher susceptible-dose dependency range. In reference to amphotericin B, optimal activity may be achieved by maximizing the peak drug concentration/MIC ratio.

Postburn serum drug binding and serum protein concentrations.

The free fractions of diazepam, imipramine, lidocaine, meperidine, phenytoin, propranolol, and salicylic acid were determined in the serum of seven burn patients (25% to 80% of their skin surface burned) about one week after the burn and in three of the patients at about four weeks following the injury. Serum protein fractions were measured by electrophoresis, and alpha-1 acid glycoprotein levels were determined. For the drugs that bind predominantly to albumin, the serum free fractions were greater in patients one week after the burn incident than in control subjects (diazepam, 0.055 vs. 0.017; phenytoin, 0.24 vs. 0.16; and salicylic acid, 0.69 vs. 0.32). The increase in free fraction for these drugs was attributed to the postburn decrease in serum albumin levels (2.2 vs. 4.4 g/dL, control). Imipramine, lidocaine, meperidine, and propranolol bind primarily to alpha-1 acid glycoprotein. The free fractions for these drugs decreased one week following the burn (imipramine, 0.074 vs. 0.095; lidocaine, 0.17 vs. 0.35; meperidine, 0.37 vs. 0.48; and propranolol, 0.045 vs. 0.107), presumably in response to the increased alpha-1 acid glycoprotein concentration (222 vs. 83 mg/dL, control). Diazepam, lidocaine, propranolol, and salicylic acid free fractions were still different from control values at four weeks after the accident.

Evaluation of seasonality in six clinical populations and two normal populations.

The Seasonal Pattern Assessment Questionnaire (SPAQ) was used to evaluate retrospectively self-reported seasonal changes in mood and behavior (seasonality) of two normal and six clinical populations: patients with winter-seasonal affective disorder (SAD), summer-SAD, eating disorders, bipolar affective disorder, major depressive disorder and subsyndromal winter-SAD. The SPAQ successfully discriminated between groups expected to have high seasonality scores, such as winter-SAD, summer-SAD and subsyndromal winter-SAD, and normal controls. Bipolars and major depressives had normal seasonality scores. Patients with eating disorders had unexpectedly high scores. There was a general tendency for all groups to eat and sleep more and to gain weight in the winter. The implications of these findings are discussed.

Pharmacokinetics and pharmacodynamics of aztreonam administered by continuous intravenous infusion.

The pharmacodynamic parameter that appears to correlate best with a successful therapeutic outcome with beta-lactam antibiotics is the length of time the serum antibiotic concentration remains above the minimum inhibitory concentration (MIC) for the infecting pathogen. By maximizing this parameter, continuous administration of beta-lactam and related antibiotics by intravenous infusion could represent the optimal mode of drug administration. The pharmacokinetic and pharmacodynamic properties of ceftazidime administered by continuous intravenous infusion have been evaluated previously. Aztreonam is a monobactam antibiotic with similar pharmacokinetic and microbiologic activity to that of ceftazidime. This study evaluated the pharmacokinetic and pharmacodynamic characteristics of aztreonam administered as a continuous intravenous infusion in healthy volunteers against multiple clinical isolates. Five men and 3 women received 6 g of aztreonam administered by continuous intravenous infusion over 24 hours. Blood samples were collected before the infusion and at 0.5, 1 through 8, 12, 18, and 24 hours after the start of the infusion. Pharmacokinetic parameters were determined by standard equations. In vitro susceptibility testing was performed using National Committee for Clinical Laboratory Standards guidelines for 4 clinical isolates of gram-negative bacteria (2 each of Escherichia coli and Pseudomonas aeruginosa). Serum inhibitory titers (SITs) were determined in duplicate for each clinical isolate at 0 and 24 hours. The subjects' mean (+/- SD) age was 29.3+/-4.4 years; mean weight, 74.6+/-14.0 kg; and calculated mean creatinine clearance, 107+/-13 mL/min. For the pharmacokinetic parameters, mean (+/- SD) values were as follows: steady-state serum concentration, 40.9+/-8.8 microg/L; half-life, 1.5+/-0.4 hours; elimination rate constant, 0.50+/-0.13 hours(-1); steady-state volume of distribution, 0.18+/-0.04 L/kg; and total body clearance, 6.1+/-1.2 L/h. The MICs were 0.0625 and 0.125 microg/mL against the 2 E coli isolates and 4 microg/mL against both P aeruginosa isolates. The median SITs against the E. coli isolates were 1:256 and 1:512, and against the P. aeruginosa isolates were 1:8 and 1:16. At steady state, II subjects had serum concentrations of aztreonam > or =4 times the MIC for each organism. These findings suggest that further clinical study of the administration of aztreonam by continuous intravenous infusion is warranted.

Pharmacokinetics and pharmacodynamics of cefepime administered by intermittent and continuous infusion.

OBJECTIVE: This study assessed the pharmacokinetics and pharmacodynamics of cefepime administered by intermittent and continuous infusion against clinical isolates of Pseudomonas aeruginosa, Enterobacter cloacae, and Staphylococcus aureus. BACKGROUND: Because beta-lactam antibiotics exhibit time-dependent bactericidal activity and lack prolonged postantibiotic effects against many bacteria, the goal of therapy is to maintain serum drug concentrations above the minimum inhibitory concentration (MIC) for the relevant pathogen over most of the dosing interval. Continuous infusion is a mode of drug administration that can provide serum drug concentrations continuously above the MIC for most bacterial pathogens. METHODS: Twelve healthy volunteers were enrolled. Each received cefepime 2 g by intermittent bolus q12h and, on another day, was randomly assigned to receive 4 or 3 g administered by continuous infusion over 24 hours. RESULTS: For the intermittent regimen, the mean (+/- SD) pharmacokinetic findings were: maximum serum concentration, 112.9 +/- 21.1 microg/mL; minimum serum concentration, 1.3 +/- 0.5 microg/mL; and half-life, 2.6 +/- 0.4 hours. For the 3- and 4-g continuous infusion regimens, steady-state serum concentrations (C(SS)) were 13.9 +/- 3.8 and 20.3 +/- 3.3 microg/mL, respectively. MICs ranged from 2 to 4, 0.125 to 8, and 2 to 8 microg/mL against P. aeruginosa, E. cloacae, and S. aureus, respectively. For the intermittent regimen, serum inhibitory titers (SITs) at 24 hours were > or = 1:2 in 46% of subjects against P. aeruginosa, 48% against E. cloacae, and 2% against S. aureus. For both continuous infusion regimens, SITs for each organism were > or = 1:2 in all subjects. CONCLUSIONS: The intermittent regimen maintained serum concentrations above the MIC for P. aeruginosa and E. cloacae in > or = 92% (11/12) of subjects for > or = 70% of the dosing interval, provided the MIC was < or = 4 microg/mL. Both continuous infusion regimens provided a C(SS) above the MIC for all organisms. However, the C(SS) was > or = 4 times the MIC only if the MIC was < or = 2 microg/mL. Only the 4-g regimen provided such concentrations against isolates with an MIC of 4 microg/mL, and neither regimen provided such concentrations when the MIC was 8 microg/mL. These findings should be applied in comparative clinical studies.

Depressive reactions to failure in a naturalistic setting: a test of the hopelessness and self-esteem theories of depression.

We tested the hopelessness and self-esteem theories of depression and an integration of the two by examining whether a stable, global attributional style (attributional diathesis) and low self-esteem interacted with the outcomes students received on a midterm examination to predict their subsequent depressive reactions over the course of 5 days. Students' immediate depressive reactions (on receipt of grades) were predicted solely by the examination outcome, whereas their enduring depressive reactions during the following 4 days were predicted by the Attributional Diathesis x Low Self-Esteem x Failure interaction. The results also indicated that the three-way interaction predicted enduring depressive reactions through the mediating role of hopelessness.

Cefepime.

Cefepime is a potent, broad-spectrum, fourth-generation cephalosporin with enhanced activity against most gram-positive aerobic bacterial pathogens and many gram-negative aerobic bacteria that are resistant to other cephalosporins. The drug's zwitterionic structure contributes to more rapid penetration of gram-negative bacterial cell membranes, and its low affinity for most type I beta-lactamases leads to significantly reduced enzymatic degradation compared with other cephalosporins. Cefepime has a good toxicity profile, with minor gastrointestinal and central nervous system symptoms being most prevalent. At dosages ranging from 1-2 g every 8-12 hours, it is an alternative option for infections of the lower respiratory tract, urinary tract, and skin and skin structures, as well as febrile episodes in neutropenic patients with cancer, and bacteremia or septicemia in critically ill patients.

Comparison of ampicillin-sulbactam and ticarcillin-clavulanic acid in patients with chronic renal failure: effects of differential pharmacokinetics on serum bactericidal activity.

STUDY OBJECTIVES: To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. DESIGN: Randomized, crossover, controlled study. SETTING: National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. PATIENTS: Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. INTERVENTIONS: On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. MEASUREMENTS AND MAIN RESULTS: The mean observed apparent beta-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-beta-lactamase-producing (N beta-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against beta-lactamase-producing (beta-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against beta-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. CONCLUSION: Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from beta-lactamase degradation.

Findings from the Seasonal Pattern Assessment Questionnaire in patients with eating disorders and control subjects: effects of diagnosis and location.

We previously reported a high degree of seasonality as measured by the Seasonal Pattern Assessment Questionnaire (SPAQ) in 41 patients with eating disorders (ED) compared with control subjects and patients with five other affective spectrum disorders. To clarify the relationship of the specific ED diagnosis and latitude to seasonal variation in a larger sample, we administered the SPAQ to 159 women with ED as defined by DSM-III-R. Subtype diagnoses were as follows: bulimia nervosa (BN), n = 109; anorexia nervosa (AN), n = 30; BN+AN, n = 20. Patients were studied at three locations: National Institute of Mental Health (NIMH), n = 46; Medical University of South Carolina (MUSC), n = 53; University of Michigan (UM), n = 60. The control group comprised 50 female normal volunteers studied at NIMH. There was a statistically significant difference in Global Seasonality Scale (GSS) scores among the four diagnostic groups, and all ED subtypes had significantly higher GSS scores than control subjects after post hoc Bonferroni t tests. Higher GSS scores were also found in patients with BN+AN compared with patients with BN or AN alone. The patterns of change were similar to those observed in winter seasonal affective disorder (SAD). Thirteen percent of the total sample of ED patients met SPAQ criteria for winter SAD, with 2.5% each for summer SAD and subsyndromal SAD. UM BN patients (latitude 42 degrees N) had higher GSS scores and a higher prevalence of winter SAD than MUSC BN patients (latitude 33 degrees N), but this difference was not statistically significant. These data support the hypothesis that ED and SAD may involve similar pathophysiological mechanisms, possibly related to serotonin dysregulation.

Biological effects of cocaine derivatives I: Improved synthesis and pharmacological evaluation of norcocaine.

An improved synthesis of norcocaine, a metabolite of cocaine, is reported. Following intravenous administration to a rhesus monkey, respiratory effects were similar to those observed following cocaine treatment. In addition, clonic convulsions, hypothermia, and mydriasis resulted. Norcocaine could be responsible for part of the pharmacological activity of cocaine.