Harold H. Harsch

Determination of Drug-Induced Changes in Functional MRI Signal Using a Pharmacokinetic Model

As the applications of functional magnetic resonance imaging (fMRI) expand, there is a need for the development of new strategies for data extraction and analysis that do not require the presentation of stimuli in a repeated on/off pattern. A description and evaluation of a method and computer algorithm for the detection and analysis of brain activation patterns following acute drug administration using fMRI are presented. A waveform analysis protocol (WAP) input function has been developed that is based upon the single‐dose pharmacokinetics of a drug of interest. As a result of this analysis, regional brain activation can be characterized by its localization and intensity of activation, onset of action, time to peak effect, and duration of action. A global statistical test for significant drug effects based upon the probability of a voxel being activated by a saline vehicle injection is applied to grouped data on a voxel by voxel basis. Representative data are presented using nicotine as a prototypical agent. Using this method, statistically significant drug‐induced brain activation has been identified in several key cortical and subcortical brain regions. Hum Brain Mapping 8:235–244, 1999.

Categorization of Types of Medical/Psychiatry Units Based on Level of Acuity

Medical/psychiatry units can be categorized by the level of acuity of medical and psychiatric illness. Type I units are categorized as those that primarily provide psychiatric care with a low level of medical acuity. Type II units include general medicine or medical subspecialty units that are associated with a psychiatric liaison service and provide low levels of psychiatric care to those admitted to the general medical setting. Type III and Type IV units are characterized by a true departure from the current ward settings and care for patients who have concurrent and more severe medical and psychiatric problems in a unified setting. Both of these units require special physical changes in the ward structure, additional nurse training, and coordinated physician coverage to function effectively.

Epidural cortical stimulation of the left dorsolateral prefrontal cortex for refractory major depressive disorder.

BACKGROUND A significant number of patients with major depressive disorder are unresponsive to conventional therapies. For these patients, neuromodulation approaches are being investigated. OBJECTIVE To determine whether epidural cortical stimulation at the left dorsolateral prefrontal cortex is safe and efficacious for major depressive disorder through a safety and feasibility study. METHODS Twelve patients were recruited in this randomized, single-blind, sham-controlled study with a 104-week follow-up period. The main outcome measures were Hamilton Depression Rating Scale-28 (HDRS), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Function (GAF), and Quality of Life Enjoyment and Satisfaction (QLES) questionnaire. An electrode was implanted over Brodmann area 9/46 in the left hemisphere. The electrode provided long-term stimulation to this target via its connections to an implanted neurostimulator in the chest. RESULTS During the sham-controlled phase, there was no statistical difference between sham and active stimulation, although a trend toward efficacy was seen with the active stimulation group. In the open-label phase, we observed a significant improvement in outcome scores for the HDRS, MADRS, and GAF but not the QLES (HDRS: df = 7, F = 7.72, P < .001; MADRS: df = 7, F = 8.2, P < .001; GAF: df = 5, F = 16.87, P < .001; QLES: df = 5, F = 1.32, P > .2; repeated measures ANOVA). With regard to the HDRS, 6 patients had ≥ 40% improvement, 5 patients had ≥ 50% improvement, and 4 subjects achieved remission (HDRS < 10) at some point during the study. CONCLUSION Epidural cortical stimulation of the left dorsolateral prefrontal cortex appears to be a safe and potentially efficacious neuromodulation approach for treatment-refractory major depressive disorder. ABBREVIATIONS DBS: deep brain stimulation DLPFC: dorsolateral prefrontal cortex ECT: electroconvulsive therapy EPCS: epidural cortical stimulation FDA: Food and Drug Administration FDG: fluorodeoxyglucose GAF: Global Assessment of Functioning HDRS: Hamilton Depression Rating Scale-28 MADRS: Montgomery-Asberg Depression Rating Scale MDD: major depressive disorder QLES: Quality of Life Enjoyment and Satisfaction questionnaire rCMRG: regional cerebral metabolic rate of glucose TMS: transcranial magnetic stimulation VNS: vagus nerve stimulation

Hepatitis C virus infection in cocaine users--a silent epidemic.

Over a recent three year period, approximately 600 individuals responded to newspaper advertisements for research studies requiring healthy, cocaine using subjects. These subjects were screened using a standard phone interview in order to eliminate individuals with known medical or psychiatric illnesses that would exclude them from ongoing neuroimaging studies of drug abuse. Individuals were specifically asked about their hepatitis and HIV status. Of these, 170 subjects passed the phone screen, having no known medical or psychiatric illness outside of cocaine abuse/dependence and were willing to be further evaluated for the studies. These subjects were brought to the Medical College of Wisconsins General Clinical Research Center and tested for, among other measures, hepatitis B, hepatitis C, and HIV. Of these, 144 completed the examination and all testing. In this cohort of assumed healthy subjects, 47 (33%) tested positive for antibodies to the hepatitis C virus (HCV). Only 7 (5%) tested positive for the hepatitis B surface antigen and 2 (1.4%) to HIV. The demographics of this cohort are 56% African-American, 81% male, 75% never-married, 55% unemployed with a mean age of 36 years. The percentage of subjects reporting any lifetime intravenous drug use among the HCV(+) and the HCV(−) cohorts was 77% vs. 29% respectively. Some routes of HCV transmission are still unclear and may reflect lifestyle or other factors related to cocaine use outside of parenteral drug use. Since almost all HCV infections become chronic, and many progress to chronic active hepatitis, cirrhosis, and ultimately hepatocellular carcinoma, these observations suggest a significant epidemic in an unsuspecting population with little regular access to health care. These individuals also form a large pool for the continued transmission of HCV to the general population. Additional public health interventions are suggested.

Inpatient unit for combined physical and psychiatric disorders

Abstract The Behavior Evaluation and Treatment Unit of the Medical College of Wisconsin provides continuous care of patients with combined behavioral and physical problems. These patients differ from those seen in our consultation service by having higher rates of psychosis, approaching that of traditional psychiatric inpatient programs. The medical and surgical illnesses treated on this unit are not trival, are often found to aggravate the psychiatric problems, and are sometimes considered causative. The work-up and treatment of such patients can potentially be performed without major increases in length of stay. Inpatient programs for combined disorders hold the promise of enhancing quality and alternatives of care for a sizable group of patients.

Gastric outlet obstruction as a late complication of formaldehyde ingestion: A case report

ABSTRACTA patient who ingested formaldehyde in a suicide attempt is described. Although early clinical and endoscopic manifestations appeared relatively mild, after several weeks the patient developed signs and symptoms suggestive of gastric outlet obstruction that eventually required surgical intervention. Formaldehyde ingestion has only rarely been described in the literature. Formaldehyde is a corrosive that can produce late sequelae, similar to the more common ingestion of acids and alkali.

Length of stay on a psychiatry-medicine unit.

To assess the efficiency of a medical-psychiatric unit over 3 years, several studies were carried out on one combined psychiatry-medicine unit. On the Behavior Evaluation and Treatment Unit of the Medical College of Wisconsin, Division of General Hospital Psychiatry, average length of stay was calculated in successive cohorts of 28-31 consecutive patients (total 358 patients). Medical-surgical and psychiatric diagnoses were compared over a 2 1/2-year span; psychiatry diagnoses were compared to those on other units; and acuity of illness was measured comparatively by various methods. Length of stay decreased from more than 20 to less than 15 days. This effect did not appear to be directly related to diagnostic changes. Only minor increases in range of psychiatric diagnostic categories and changes in proportion of certain disorders were found. The acuity level was descriptively intermediate between that of a general medicine and that of a general psychiatry unit. Factors that could be related historically to these findings were discussed.

The Role of Empathy in Medical Students’ Choice of Specialty

The role of empathy in medical students’ postgraduate training interest was studied. The level of empathy, as measured by the Hogan Empathy Scale, was not found to be a discriminating factor in career selection. Students interested in psychiatry had empathy levels similar to other groups of students. Although empathy has been suggested as a possible discriminating variable among medical school candidates, individuals with high and low empathy scores were found to be interested in every field of practice. Further studies are needed before measurement of empathy is used in the selection process for medical school admission.

A profile of academic medical-psychiatric units

Medical-psychiatric inpatient programs are a relatively recent phenomenon. Although interest in these programs seems widespread, they are still found primarily at academic medical centers. The authors surveyed 11 such academic units. Variations found between their patient populations, milieu, and organization suggest that these programs, in general, are still in an early stage of evolution. It is hoped that these data will provide a descriptive base of how these programs have developed.

Induction of mania by L-dopa in a nonbipolar patient.

The authors present a case of mania associated with the prolonged ingestion of large doses of L-dopa. Prior reports relating L-dopa therapy to mania in patients with bipolar disorders are discussed. The induction of a classic manic syndrome by catecholamine augmentation is possible in a nonbipolar individual.