Faculty Bibliography

The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder-especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other

This article reports on the development and reliability of the Diagnostic Interview for Genetic Studies (DIGS), a clinical interview especially constructed for the assessment of major mood and psychotic disorders and their spectrum conditions. The DIGS, which was developed and piloted as a collaborative effort of investigators from sites in the National Institute of Mental Health (NIMH) Genetics Initiative, has the following additional features: (1) polydiagnostic capacity; (2) a detailed assessment of the course of the illness, chronology of psychotic and mood syndromes, and comorbidity; (3) additional phenomenologic assessments of symptoms; and (4) algorithmic scoring capability. The DIGS is designed to be employed by interviewers who exercise significant clinical judgment and who summarize information in narrative form as well as in ratings. A two-phase test-retest (within-site, between-site) reliability study was carried out for DSM-III-R criteria-based major depression, bipolar disorder, schizophrenia, and schizoaffective disorder. Reliabilities using algorithms were excellent (0.73 to 0.95), except for schizoaffective disorder, for which disagreement on estimates of duration of mood syndromes relative to psychosis reduced reliability. A final best-estimate process using medical records and information from relatives as well as algorithmic diagnoses is expected to be more reliable in making these distinctions. The DIGS should be useful as part of archival data gathering for genetic studies of major affective disorders, schizophrenia, and related conditions

The acquaintanceship procedure is a method for obtaining a control group matched to relatives of probands on demographic variables. Relatives are asked to name six acquaintances who are the same gender, and who are about the same age and social class as themselves. An acquaintance is randomly selected from this list and contacted for recruitment. Rates of mental disorder in this group are assumed to approximate general population rates in a group with these demographic characteristics. This report focuses on an extension of the acquaintanceship procedure in which 'super-normal' controls are used in a family study design. Two questions were addressed: (1) Does the acquaintance group (n = 166), as a whole, show a higher rate of illness than the relatives of acquaintances with no mental disorder (n = 129)? (2) Is there a relationship between mental disorder in acquaintances and in providers of acquaintance names? The prevalence of mental illness was significantly greater among acquaintances compared to relatives of 'never ill' acquaintances. There was no evidence of assortative selection. We concluded that using the relatives of well acquaintances is a cost-effective control selection methodology which maximizes the detection of intergenerational transmission in family studies of mental disorder

We measured cerebrovascular reactivity to carbon dioxide in the cerebral cortex and the subcortical white matter of 12 healthy adult volunteers (four young subjects aged 21-24, four middle-aged subjects aged 34-40, and four elderly subjects aged 62-85 years). Blood flow was computed from the concentration history of xenon-133 in the volume of interest measured with an ultrapure germanium detector array. End-tidal PaCO2 ranged from 35.4 to 42.6 mm Hg. The mean +/- SD baseline blood flows in the cerebral cortex were 60 +/- 7, 51 +/- 9, and 33 +/- 4 ml/100 cm3/min in the young, the middle-aged, and the elderly subjects, respectively; the corresponding subcortical white matter baseline blood flows were 21 +/- 1, 22 +/- 3, and 16 +/- 5 ml/100 cm3/min. Mean +/- SD cerebrovascular reactivities to carbon dioxide in the cerebral cortex were 2.03 +/- 0.58, 1.36 +/- 0.41, and 0.72 +/- 0.19 ml/100 cm3/min/mm Hg PaCO2 for the young, the middle-aged, and the elderly subjects, respectively; the corresponding reactivities in the subcortical white matter were 0.69 +/- 0.11, 0.59 +/- 0.17, and 0.36 +/- 0.41 ml/100 cm3/min/mm Hg PaCO2. Blood flow and cerebrovascular reactivity in the cerebral cortex of the young subjects were significantly higher than those for white matter and significantly higher than those in the elderly subjects (p less than 0.001). Age vs. blood flow (for the cortex) and age vs. cerebrovascular reactivity (for both cortical gray and subcortical white matter) also showed significant linear correlation (p less than 0.05). However, the age-related changes in white matter blood flow and cerebrovascular reactivity were slow, and the differences among the age groups were not statistically significant

The hysteresis of prototype aneurysm clips made from either titanium alloy (Ti-6Al-4V) or Elgiloy (Co-Ni) have been compared. If aneurysm clips are opened too wide during insertion, stresses in excess of the yield strength of the material can be applied, causing hysteresis and uncertainty in the actual closing force. In this work, the authors demonstrated that, although mechanical test data on different alloys give useful guidance to the alloys' suitability of withstanding such loading, it is the design and geometric section of the device that determine the stress applied. Aneurysm clips formed from the two alloys were compared at maximum recommmended extension using a Digital Force Gage to monitor the load applied, and yielding was demonstrated in certain aneurysm clip configurations. Consequently, it is clearly possible to overstress the clips, even using recommended procedures. Both the increase and decrease of the closing force of the clip after overstressing its spring are indicative of relaxation of residual stresses. This is unpredictable and therefore dangerous. It would be desirable for manufacturers to specify a value for the closing force of the clip after it has been opened to its maximum which could be used as a standard for surgeons. Regulatory agencies or neurosurgeons would therefore clearly benefit from improved standardization of calibration procedures for such clips

Pentoxifylline has been shown to improve treadmill walking distances under blinded, controlled conditions in patients with intermittent claudication. From the pooled data of a blinded, controlled, randomized, multicenter trial, the data from all enrolled patients with severe claudication (less than 70 m on treadmill at baseline) were evaluated. The treadmill data from these more severely ill patients were analyzed separately as a 'severe subset' (placebo n = 17; pentoxifylline n = 21). No differences between the two treatment groups were observed in demography, history, or baseline treadmill walking distances. The initial claudication distance (ICD) improved 68% over baseline with pentoxifylline and 12% with placebo (p = .012) after twenty-four weeks of treatment. A new, derived efficacy variable was developed, 'minimum distance walked,' which tended to minimize psychological effects on treadmill performance. Over sixteen to twenty-four weeks of treatment, the pentoxifylline group improved 49% over baseline and the placebo group 3% (p = .019), when the 'minimum distance walked' measurement was used. In this controlled trial the subset of patients with severe intermittent claudication benefited from pentoxifylline therapy

Distribution of cerebral blood flow was measured with an array of 200 ultra-pure germanium radiation detectors and 133-Xe by inhalation. The array 'sees' the head as a composite of different subvolumes and enables measurement of the concentration history of tracer every 1-10 sec in each subvolume simultaneously. Subvolume mean flows, (fm), and partition coefficients, lambda m, are derived by compartmental analysis of tissue concentration washout curves. Errors from 'cross talk,' scalp radiation, 'look through,' and assumed partition coefficients are eliminated. Average fm adjusted for 40 mm Hg PACO2 in 14 cortical subvolumes (7 right, 7 left) of four normal 21-24 year old controls ranged from 50 to 60 ml/100 cc tissue/min, and lambda m ranged from 0.97 to 1.14. Average fm and lambda m in white matter was 24 ml/100 cc/min and 1.42 - 1.14 respectively. During CO2 inhalation, right and left hemispheric fm increased 6.4% and 5.7%/mm Hg respectively, whereas white matter fm increased 2.2% and 3.4% mm Hg respectively. There was no systematic difference between front and back or dominant vs non-dominant sides. Three 73-84 year old controls had reduced fm and CO2 reactivity in all subvolumes, lambda m was in the same range as in younger controls. Two patients with intracranial cerebrovascular disease showed excellent localization of ischemic subvolumes. One patient with asymptomatic unilateral 98% stenosis of the internal carotid artery had a similar distribution of blood flow in both hemispheres

Pentoxifylline, a methyl xanthine analogue was evaluated for treatment of intermittent claudication in a double-blind placebo controlled parallel group study in seven centers in the United States. Tests were performed on 128 cases, including 42 who took pentoxifylline (600 mg by mouth daily, increased stepwise to 1200 mg daily at the end of one month) and 40 who took placebo for 24 weeks. Twenty-five patients on pentoxifylline and 21 on placebo were dropped from the study for reasons unrelated to the drug. Walking ability on a treadmill was increased significantly after 2 weeks and remained so throughout the study in the pentoxifylline vs. the placebo group. Ability to walk until first experiencing intermittent claudication was a more sensitive index than the maximum ability to walk. The drug did not cause changes in blood pressure or in heart rate. Other than mild nausea, there were no significant side effects.