Relationship between clinical and radiological diagnostic criteria for Alzheimer's disease and the extent of neuropathology as reflected by 'stages': a prospective study

The distribution of pathology related to Alzheimer's disease (AD) is not uniform throughout the brain. Sites which have a predilection for the development of Alzheimer-type pathology are the limbic regions and neocortical association areas. The changes in these areas of the brain develop gradually, following a well-determined sequence that allows a pathological staging of the disease process. According to the staging hypothesis, the first pathological alterations develop in the transentorhinal and entorhinal regions. The neurofibrillary pathology then spreads into the hippocampus, but not until the final stages does it affect the neocortex. In this study we analyse the relationship between the pathological stages of AD, according ot the staging hypothesis, and the clinical diagnosis in a prospectively assessed patient group. Prediction of any given pathological stage from the clinical diagnosis was found to be poor. This may be partly due to the fact that additional pathologies can alter the clinical picture and severity of dementia in patients who are only in the initial stages of AD. Nevertheless, the NINCDS-ADRDA clinical criteria had a high sensitivity for detection of AD-related pathology: the 'probable AD' category included 22/38 (57.9%) of those in the late isocortical stage, while the 'possible AD' category included 19/23 (82.6%) of those in the limbic stage. Using proposed neuro-imaging protocols for improved identification of patients with AD-related pathology, we largely identified subjects in whom the extent of pathology had spread to the neocortex.     

Radiation burden to paediatric patients due to micturating cystourethrography examinations in a Dutch children's hospital

Micturating cystourethrography (MCU) examinations of paediatric patients in a major Dutch children's hospital (JKZ) were evaluated to generate quantitative information on effective dose (E). A standard examination involves three radiographs plus fluoroscopy. Observed total dose-area product (DAP) for 84 children increased, on average, with increasing age class from 0.2 to 2.2 Gy cm2. In 11 cases, separate DAP per view was measured; enabling determination, per view, of organ (CF) and effective (CE) dose conversion factors, i.e. dose per unit of DAP. Monte Carlo simulation of photon transport in male and female mathematical phantoms was applied for newborn, 1 year, 5 year, 10 year and 15-year-old patients, and interpolated for other ages. CE per view decreases with increasing age class, yielding about a factor of 10 difference between the extremes of the range. Female values are usually some 20-30% above male ones. CE for one of the views appeared to be representative for the complete examination and was used to estimate total E for each patient. Averaged per age class, E remains approximately constant at 0.3-0.4 mSv, although a tendency to increase with increasing age exists, for females in particular. Within an age class, individual patients may differ in E by a factor of two up to six. Stomach, lower large intestine, bladder wall, liver and ovaries receive relatively high doses. Compared with published data and DAP measured in a few other Dutch hospitals, the radiation burden of MCU is low at the JKZ. This indicates a good degree of optimization with respect to radiation protection (e.g. modern equipment, increased tube voltage, fast film-screen combination).     

Incomplete intertrochanteric fractures: imaging features and clinical management

PURPOSE: To present the imaging findings and treatment options for incomplete intertrochanteric fractures. MATERIALS AND METHODS: Among 31 patients with the magnetic resonance (MR) imaging diagnosis of incomplete intertrochanteric fracture, 30 also underwent radiography. MR and radiographic findings were compared. Note was made of fracture length and extent as depicted on the coronal and axial MR images, treatment (surgical vs conservative), and follow-up. RESULTS: Correlation between radiographic and MR findings was poor. Incomplete intertrochanteric fracture was the prospective radiographic diagnosis in only one case. Fracture in 18 patients was treated surgically and in 13 was managed conservatively. In both groups, the average age of the patients and length of the fractures and the percentage of separate fractures involving the greater trochanter and crossing the midline of the femur in the axial plane were the same. Fractures crossed the midline in the coronal plane in 50% of the surgical group but in only 23% of the nonsurgical group. Average time from injury to ambulation was 2 days less in the surgical group, but no difference in functional status was found subjectively between the two groups at clinical follow-up. CONCLUSION: Incomplete intertrochanteric fractures are a previously unrecognized subset of intertrochanteric fractures that are diagnosed unequivocally only with MR imaging.     

Patterns of early lexical and cognitive development in premature and full-term infants

The linguistic and cognitive development of 26 premature and 27 full-term infants was studied longitudinally over the first 3 years of life. Infants in the premature population included 12 who were below 1500 g in birthweight and an even larger number with "at risk" signs. Language samples were collected in the home approximately every other month, the children were given experimenter-designed tests periodically, and mothers were asked to keep diaries of their children's lexical development. The children were given standardized tests as they exited the study. Cognitive development was also measured periodically. The patterns of lexical and cognitive development of the prematures did not differ markedly from those of full-term infants. There were no significant differences between the prematures as a whole and the full-term infants on standard language test measures as they exited from the study. There were significant differences between the very low birthweight and full-term infants on two of the exit measures. However, the performance of the very low birthweight infants was well within the range of normal on these two measures. The nature of the study and the factors that might have led to lack of differences between the two groups are discussed.     

The fate of the untreated alcoholic. Toward a natural history of the disorder.

Eighty-three male alcoholics were administered a structured interview when they appeared at a large general hospital for treatment of a variety of disorders. These represent 83 consecutive cases. None received treatment aside from brief "drying-out" but all were accepted as participants in a research program. Seventy-three (88 per cent of the sample) were located for a 3-year follow-up; five of these were not seen at the 1-year follow-up, and 10 were known to be dead. This paper focuses on 58 of the alcoholics who were seen at all three evaluations, and the 10 who were known dead. The data are presented as indicating the long term results of, at best, a mild or minimal intervention with male alcoholics. A small, but significant improvement was noted on several life-adjustment scales between the initial and 1-year evaluation (OYE), but no further improvement was seen between OYE and the 3-year evaluation (TYE); 19 percent were abstinent for 1 year and 10 per cent for the full 3-year period. The best predictor of TYE abstinence was OYE abstinence, but only for the extremes, i.e., no abstinence or total abstinence. Abstinence success was also related to a tendency to use community resources, lower number of mental hospitalizations, higher occupational status, higher global rating and, curiously, lower interpersonal adjustment rating. The group using Alcoholics Anonymous showed no better outcome than the group using no community resources at all. The mortality rate was 12 per cent over the 3 years or slightly more than 4 per cent a year. The suicide rate was about 4 per cent over the 3 years. The ratings for those dying showed a pattern of more admitted drunken arrests and heavy recent drinking superimposed on lighter overall drinking for the past year. The study demonstrates that even untreated alcoholics can be traced and effective follow-up studies completed. Results also indicate that over long time periods and left to their own devices, many alcoholics do seek out some form of help. But such assistance tends not to be sustained or intensive and a good portion of it is nonprofessional and nonmedical. Moreover, a surprisingly substantial number (31 per cent) of hospital-identified alcoholics apparently neither seek out nor receive any help at all after their initial identification; yet their self-reported life-adjustment ratings do not differ significantly from those who do seek help. The no-help receivers may be the most critical group of all to follow, as they are trule untreated. It would be important to determine how consistent in fact they are in their avoidance of help, what accounts for that behavior, and whether their ultimate fate is different from those who regularly seek assistance.     

Nortriptyline versus fluoxetine in the treatment of depression and in short-term recovery after stroke: a placebo-controlled, double-blind study

OBJECTIVE: This study compared nortriptyline and fluoxetine with placebo in the treatment of depression and in recovery from physical and cognitive impairments after stroke. METHOD: A total of 104 patients with acute stroke enrolled between 1991 and 1997 entered a double-blind randomized study comparing nortriptyline, fluoxetine, and placebo over 12 weeks of treatment. The majority of patients were recruited from a rehabilitation hospital in Des Moines, Iowa, but other enrollment sites were also used. Both depressed and nondepressed patients were enrolled to determine whether improved recovery could be mediated by mechanisms unrelated to depression. Nortriptyline in doses of 25 mg/day gradually increased to 100 mg/day or fluoxetine in doses of 10 mg/day gradually increased to 40 mg/day or identical placebo were given over 12 weeks. Response to treatment of depression for individual patients was defined as a greater-than-50% reduction in scores on the Hamilton Rating Scale for Depression and no longer fulfilling diagnostic criteria for major or minor depression. Improved recovery for a treatment group was defined as a significantly higher mean score from baseline to end of the treatment trial, compared with patients treated with placebo, on measures of impairment in activities of daily living and levels of cognitive and social functioning. RESULTS: Nortriptyline produced a significantly higher response rate than fluoxetine or placebo in treating poststroke depression, in improving anxiety symptoms, and in improving recovery of activities of daily living as measured by the Functional Independence Measure. There was no effect of nortriptyline or fluoxetine on recovery of cognitive or social functioning among depressed or nondepressed patients. Fluoxetine in increasing doses of 10-40 mg/day led to an average weight loss of 15. 1 pounds (8% of initial body weight) over 12 weeks of treatment that was not seen with nortriptyline or placebo. CONCLUSIONS: Given the doses of medication used in this study, nortriptyline was superior to fluoxetine in the treatment of poststroke depression. Demonstrating a benefit of antidepressant treatment in recovery from stroke may require the identification of specific subgroups of patients, alternative measurement scales, or the optimal time of treatment.