Photodynamic therapy with methyl aminolaevulinate 80 mg g(-1) for severe facial acne vulgaris: a randomized vehicle-controlled study.

BACKGROUND: Severe acne vulgaris has limited therapeutic options. OBJECTIVES: To evaluate photodynamic therapy (PDT) using topical methyl aminolaevulinate (MAL, 80 mg g(-1) ) as the photosensitizer in severe facial acne. METHODS: A double-blind, randomized, vehicle-controlled multicentre trial in 153 patients (aged 12-35 years) with severe facial acne [Investigator's Global Assessment (IGA) score 4; 25-75 inflammatory lesions with ≤ 3 nodules; 20-100 noninflammatory lesions]. Treatment (four treatments 2 weeks apart) involved incubation with MAL (n = 100) or vehicle cream (n = 53) for 1·5 h under occlusion, then illumination (635-nm red light, total dose 37 J cm(-2) ). IGA assessment and standardized lesion counts were performed before each treatment and 12 weeks after the first treatment. Treatment success was defined as improvement from baseline in IGA by ≥ 2 grades at 12 weeks. Safety assessments were for pain (10-cm visual analogue scale, immediately after illumination), erythema (four-point rating scale) and adverse events. RESULTS: At 12 weeks, PDT using MAL 80 mg g(-1) reduced inflammatory lesions vs. vehicle PDT (mean change -15·6 vs. -7·8, P = 0·006; mean percentage change -37·3% vs. -16·2%, P = 0·003). However, noninflammatory lesions did not decrease significantly (mean change -11·8 vs. -10·7, P = 0·85; mean percentage change -28·6% vs. -24·9%, P = 0·72). Treatment success rates were greater with MAL-PDT 80 mg g(-1) (44% vs. 26%, P = 0·013). Pain was low and manageable by briefly pausing illumination. There was similar pain or erythema with successive treatments. CONCLUSIONS: PDT using topical MAL 80 mg g(-1) and red light may offer promise for severe acne vulgaris.

Conceptual competence in psychiatric training: building a culture of conceptual inquiry.

Building a culture of conceptual inquiry in psychiatric training requires the development of conceptual competence: the ability to identify and examine assumptions that constitute the philosophical foundations of clinical care and scientific investigation in psychiatry. In this article, we argue for the importance of such competence and illustrate approaches to instilling it through examples drawn from our collective experiences as psychiatric educators.

Cervical artery dissection related to chiropractic manipulation: One institution's experience.

PURPOSE: The purpose of this study was to determine the frequency of patients seen at a single institution who were diagnosed with a cervical vessel dissection related to chiropractic neck manipulation. METHODS: We identified cases through a retrospective chart review of patients seen between April 2008 and March 2012 who had a diagnosis of cervical artery dissection following a recent chiropractic manipulation. Relevant imaging studies were reviewed by a board-certified neuroradiologist to confirm the findings of a cervical artery dissection and stroke. We conducted telephone interviews to ascertain the presence of residual symptoms in the affected patients. RESULTS: Of the 141 patients with cervical artery dissection, 12 had documented chiropractic neck manipulation prior to the onset of the symptoms that led to medical presentation. The 12 patients had a total of 16 cervical artery dissections. All 12 patients developed symptoms of acute stroke. All strokes were confirmed with magnetic resonance imaging or computerized tomography. We obtained follow-up information on 9 patients, 8 of whom had residual symptoms and one of whom died as a result of his injury. CONCLUSION: In this case series, 12 patients with newly diagnosed cervical artery dissection(s) had recent chiropractic neck manipulation. Patients who are considering chiropractic cervical manipulation should be informed of the potential risk and be advised to seek immediate medical attention should they develop symptoms.

Live volumetric (4D) visualization and guidance of in vivo human ophthalmic surgery with intraoperative optical coherence tomography.

Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon's capabilities.

Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.

BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

The 24-hour pattern of prolactin secretion in depressed and normal adolescents.

Plasma prolactin concentrations were measured at 20-min intervals over a 24-hr period in 49 adolescents with major depressive disorder (MDD) and 39 normal control adolescents. Neither the pattern nor the amount of prolactin secretion was significantly different between these two groups. There were significant gender differences, with girls secreting more prolactin than boys, but no significant gender-by-diagnosis interactions were found. With the possible exception of psychosis, dividing the MDD sample based on clinical characteristics failed to reveal differences. These findings are discussed in the context of changes in prolactin in childhood depression using a serotonergic challenge study, as well as in relation to baseline prolactin studies in adult depression.

Nocturnal urinary excretion of 6-hydroxymelatonin sulfate in prepubertal major depressive disorder.

Levels of the melatonin metabolite, 6-hydroxymelatonin sulfate, were measured in overnight urine from 31 prepubertal children with major depressive disorder and 15 normal control children with very low family loading for affective disorder. The two groups did not differ with regard to their nocturnal excretion of this compound, nor was any depressive subgroup identified whose 6-hydroxymelatonin sulfate excretion differed from that of the control group. Previous studies of pineal function in depression are reviewed and discussed in the context of the present investigation.

Corticotropin-releasing hormone challenge in prepubertal major depression.

This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.

Fluoxetine for childhood anxiety disorders.

OBJECTIVE: The objective of this open study was to determine the efficacy and safety of fluoxetine for the treatment of children and adolescents with anxiety disorders. METHOD: Twenty-one patients with overanxious disorders, social phobia, or separation anxiety disorder, who were unresponsive to previous psychopharmacological and psychotherapeutic interventions, were treated openly with fluoxetine for up to 10 months. Patients with lifetime histories of obsessive-compulsive disorder (OCD) or panic disorder, or with current major depression, were excluded. Beneficial and adverse effects of fluoxetine were ascertained using the improvement and severity subscales of the Clinical Global Impression Scale (CGIS) in two ways: (1) independent chart reviews by two child psychiatrists and (2) prospective assessments by the treating nurses and the patients' mothers. RESULTS: Eighty-one percent (n = 17) of patients showed moderate to marked improvement in anxiety symptoms. The severity of anxiety as measured by the CGIS was also significantly reduced from marked to mild (effect size: 2.3). There were no significant side effects. CONCLUSIONS: These results suggest that fluoxetine may be an effective and safe treatment for nondepressed children and adolescents with anxiety disorders other than OCD and panic disorder. Future investigations using double-blind, placebo-controlled methodologies are warranted.

Hormonal responses to dextroamphetamine in depressed and normal adolescents.

Because of its neuroendocrine effects, amphetamine infusion has been used as a probe to investigate neurobiological correlates of depressive illness. In two separate studies, a total of 72 adolescents with major depressive disorder and 66 normal adolescents were given dextroamphetamine, 0.15 mg/kg, intravenously. Their cortisol, growth hormone, and prolactin responses were measured. These endocrine responses did not reliably distinguish adolescents with major depressive disorder from those without it, nor did they reliably delineate any specific depressive subgroup. These findings are compared with those from similar studies of adult depression.

A randomized, controlled trial of amitriptyline in the acute treatment of adolescent major depression.

OBJECTIVE: To determine amitriptyline's (AMI) efficacy in the acute treatment of adolescent major depressive disorder (MDD). METHOD: Subjects aged 12 through 17 years meeting Research Diagnostic Criteria for MDD, diagnosed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), participated in a 2-week placebo-washout followed by an 8-week, randomized, double-blind, parallel-design, placebo-controlled trial of AMI, 5 mg/kg per day. The K-SADS nine-item scale, the Hamilton Depression Rating Scale, and the Clinical Global Impressions rating scale were used as outcome measures. RESULTS: Thirty-one subjects were randomized (18 AMI, 13 placebo). Twenty-two subjects were study completers (12 AMI, 10 placebo). AMI's efficacy was suggested by the Clinical Global Impressions but not the K-SADS-derived data. Perhaps the primary limitation of the current study is its small sample size. CONCLUSION: No definitive recommendation can be made regarding the efficacy of tricyclic antidepressants in the treatment of adolescent MDD.

Randomized, controlled trial of amitriptyline versus placebo for adolescents with "treatment-resistant" major depression.

OBJECTIVE: To assess the response to a serotonergic/noradrenergic tricyclic antidepressant, amitriptyline (AMI), in a group of adolescents with treatment-resistant major depressive disorder (MDD). METHOD: Twenty-seven depressed adolescents admitted to a state hospital underwent a 10-week randomized, controlled trial with a flexible dose of AMI or placebo. RESULTS: There were no differences between patients taking AMI (n = 13) and placebo (n = 14). Both treatment groups showed approximately 70% to 80% improvement on the clinical outcome measurements, and 65% to 70% showed functional improvement. At the end of the protocol, 30% of patients still fulfilled criteria for MDD and had impaired functioning. Patients taking AMI experienced significantly more dry mouth and tachycardia. The final AMI dose was 173.1 mg/day +/- 56.3 mg/day; blood levels were 226.2 ng/mL +/- 80.8 ng/mL. CONCLUSIONS: No significant differences were found between AMI and placebo, in part because of the high placebo response rate. Although both treatment groups showed substantial response, at the end of treatment a substantial proportion of patients still had MDD of subsyndromal symptoms of depression. This and other studies of tricyclic antidepressants question the use of this medication as first-line treatment for youths with MDD.

Women with eating problems: a community survey.

A survey was conducted of the eating habits and attitudes of a sample of young adult women. Each woman was asked whether she considered herself to have an eating problem. The sample comprised 369 attenders at a family planning clinic. Self-report assessment procedures were used, including the Eating Attitudes Test (EAT) and the General Health Questionnaire (GHQ). Eating problems were reported by 20.6 per cent of the sample. Factors which strongly discriminated between those with an eating problem and the remainder were binge eating and a high score on the EAT. Other important factors were laxative use and high levels of psychological morbidity. Self-induced vomiting was only weakly associated with reporting an eating problem, and past and present weight were unrelated to such reports.

Pigmented skin lesions in the elderly: considerations in the differential diagnosis.

Malignant melanoma affects all age groups, but its highest age-specific incidence is in the elderly. Early diagnosis depends on the ability to identify potential precursor lesions and subtle changes in melanocytic nevi indicative of malignant degeneration. Familiarity with the clinical appearance of the common benign pigmented lesions is essential to minimize unnecessary biopsy procedures. Certain clues aid the differential diagnosis and enhance early recognition, which is presently the most effective means of reducing both the morbidity and mortality from this most ominous of skin cancers.

Malignant melanoma: management guidelines.

The incidence of primary melanoma of the skin, once rare, has been increasing rapidly over the past few decades. Although it accounts for only 3% of all primary cutaneous malignancies, melanomas are responsible for two thirds of skin cancer-related deaths. Fortunately, early detection and surgical removal have resulted in a concomitant improvement in overall survival. Ongoing clinical trials are addressing various therapeutic alternatives, as well as whether any treatment modality will significantly increase response rates and survival in patients with advanced disease. These prospects are discussed, and current prognostic factors and available therapies reviewed.

Herpes zoster infection with trigeminal and facial nerve involvement.

In most cases, herpes zoster (shingles) infections are benign and self-limited, requiring no treatment. However, if patients are elderly or immuno-compromised, they are at increased risk of complications such as visceral dissemination, cranial and nerve palsies, ophthalmic zoster, and postherpetic neuralgia. We present a case of herpes zoster infection complicated by both motor and sensory involvement in an elderly man.

The six most essential questions in psychiatric diagnosis: a pluralogue part 1: conceptual and definitional issues in psychiatric diagnosis.

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM - whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article will take up the first two questions. With the first question, invited commentators express a range of opinion regarding the nature of psychiatric disorders, loosely divided into a realist position that the diagnostic categories represent real diseases that we can accurately name and know with our perceptual abilities, a middle, nominalist position that psychiatric disorders do exist in the real world but that our diagnostic categories are constructs that may or may not accurately represent the disorders out there, and finally a purely constructivist position that the diagnostic categories are simply constructs with no evidence of psychiatric disorders in the real world. The second question again offers a range of opinion as to how we should define a mental or psychiatric disorder, including the possibility that we should not try to formulate a definition. The general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.

The six most essential questions in psychiatric diagnosis: a pluralogue part 2: Issues of conservatism and pragmatism in psychiatric diagnosis.

In face of the multiple controversies surrounding the DSM process in general and the development of DSM-5 in particular, we have organized a discussion around what we consider six essential questions in further work on the DSM. The six questions involve: 1) the nature of a mental disorder; 2) the definition of mental disorder; 3) the issue of whether, in the current state of psychiatric science, DSM-5 should assume a cautious, conservative posture or an assertive, transformative posture; 4) the role of pragmatic considerations in the construction of DSM-5; 5) the issue of utility of the DSM--whether DSM-III and IV have been designed more for clinicians or researchers, and how this conflict should be dealt with in the new manual; and 6) the possibility and advisability, given all the problems with DSM-III and IV, of designing a different diagnostic system. Part I of this article took up the first two questions. Part II will take up the second two questions. Question 3 deals with the question as to whether DSM-V should assume a conservative or assertive posture in making changes from DSM-IV. That question in turn breaks down into discussion of diagnoses that depend on, and aim toward, empirical, scientific validation, and diagnoses that are more value-laden and less amenable to scientific validation. Question 4 takes up the role of pragmatic consideration in a psychiatric nosology, whether the purely empirical considerations need to be tempered by considerations of practical consequence. As in Part 1 of this article, the general introduction, as well as the introductions and conclusions for the specific questions, are written by James Phillips, and the responses to commentaries are written by Allen Frances.