Change in cervical length after prophylactic cerclage.

OBJECTIVE: To determine changes in length of incompetent cervices after cerclage, using transvaginal ultrasound. METHODS: Patients were enrolled in a prospective, observational study under an Institutional Review Board-approved protocol. McDonald or Shirodkar sutures were placed according to physician preference. Pre- and postcerclage cervical lengths were measured within 72 hours of the procedure. At each examination, the first measurement was discarded, and a mean of the subsequent three measurements was calculated. RESULTS: Twenty-one Shirodkar and ten McDonald operations were done. The mean (+/- standard deviation) precerclage cervical length was 2.7+/-0.9 cm and the postcerclage cervical length was 3.6+/-0.9 cm (P<.001, paired t test). CONCLUSION: Prophylactic cerclage results in measurable increases in cervical length, which might contribute to the success of the procedure. Further study is needed to determine whether the degree of cervical lengthening after cerclage predicts term delivery.

Synthesis and structure-activity relationships of CP-122,721, a second-generation NK-1 receptor antagonist.

The synthesis and SAR of benzylamine side chain analogs of the NK-1 receptor antagonist CP-99,994 are described. The 5-trifluoromethoxy analog, CP-122,721, shows superior in vivo blockade of NK-1 receptor mediated responses.

Slowed lexical access in nonfluent aphasia: a case study.

A list priming paradigm (LPP) was used to examine the hypothesis that nonfluent aphasics are literally slowed down in automatic access to lexical information. In this paradigm, words are presented visually, and the subject's task is to make a lexical decision on each word as quickly as possible after its presentation. As soon as a lexical decision is made on one word, that word is removed and, after a predetermined interword interval, the next word is presented. In this way, a continuous "list" effect is obtained. Prior studies with both college-age and elderly subjects using the LPP have shown that, independently of age, on the LPP, priming obtains at interword delays of 500 to 800 msec, but not at either shorter or longer interword delays. In the study reported here, the LPP was used to examine delays at which priming obtained for LD, a nonfluent aphasic with a lesion primarily in the left frontal region. Examining interword delays ranging from 500 to 1800 msec, the subject showed priming only at a delay of 1500 msec, a considerably longer delay than that at which neurologically intact subjects have shown priming. Based on these results, it is argued that while automatic access is retained, that access is much slower in a nonfluent aphasic than in neurologically intact elderly subjects. These results are discussed in terms of how slowed lexical access might impact on discourse comprehension.

Overregularization in language acquisition.

Children extend regular grammatical patterns to irregular words, resulting in overregularizations like comed, often after a period of correct performance ("U-shaped development"). The errors seem paradigmatic of rule use, hence bear on central issues in the psychology of rules: how creative rule application interacts with memorized exceptions in development, how overgeneral rules are unlearned in the absence of parental feedback, and whether cognitive processes involve explicit rules or parallel distributed processing (connectionist) networks. We remedy the lack of quantitative data on overregularization by analyzing 11,521 irregular past tense utterances in the spontaneous speech of 83 children. Our findings are as follows. (1) Overregularization errors are relatively rare (median 2.5% of irregular past tense forms), suggesting that there is no qualitative defect in children's grammars that must be unlearned. (2) Overregularization occurs at a roughly constant low rate from the 2s into the school-age years, affecting most irregular verbs. (3) Although overregularization errors never predominate, one aspect of their purported U-shaped development was confirmed quantitatively: an extended period of correct performance precedes the first error. (4) Overregularization does not correlate with increases in the number or proportion of regular verbs in parental speech, children's speech, or children's vocabularies. Thus, the traditional account in which memory operates before rules cannot be replaced by a connectionist alternative in which a single network displays rotelike or rulelike behavior in response to changes in input statistics. (5) Overregularizations first appear when children begin to mark regular verbs for tense reliably (i.e., when they stop saying Yesterday I walk). (6) The more often a parent uses an irregular form, the less often the child overregularizes it. (7) Verbs are protected from overregularization by similar-sounding irregulars, but they are not attracted to overregularization by similar-sounding regulars, suggesting that irregular patterns are stored in an associative memory with connectionist properties, but that regulars are not. We propose a simple explanation. Children, like adults, mark tense using memory (for irregulars) and an affixation rule that can generate a regular past tense form for any verb. Retrieval of an irregular blocks the rule, but children's memory traces are not strong enough to guarantee perfect retrieval. When retrieval fails, the rule is applied, and overregularization results.

Retinocalcarine function in Alzheimer's disease. A clinical and electrophysiological study.

Impaired visual function in Alzheimer's disease (AD) could result from either precortical or cortical lesions, or both. In a parallel psychophysical study of visual function in AD, we found that contrast sensitivity function, color vision, stereoacuity, and backward masking were impaired relative to the performance of age-matched control subjects, whereas performance on a critical flicker fusion test was normal. The intent of the present study was to determine whether abnormalities of the retinocalcarine pathway contribute to visual dysfunction. We performed neuro-ophthalmological examinations on 38 patients with AD; from this group, 25 received additional psychophysical testing and 13 underwent electrophysiological testing. Clinical neuro-ophthalmological examinations, full-field electroretinograms, focal electroretinograms, and pattern visual evoked potentials were normal in all patients tested. There was no evidence of retinocalcarine abnormality specific to AD. We conclude that the visual impairment experienced by some patients with AD primarily results from involvement of the visual association cortices rather than from precortical damage, at least before the end stage of the disease.

Iofetamine I 123 single photon emission computed tomography is accurate in the diagnosis of Alzheimer's disease.

To determine the diagnostic accuracy of iofetamine hydrochloride I 123 (IMP) with single photon emission computed tomography in Alzheimer's disease, we studied 58 patients with AD and 15 age-matched healthy control subjects. We used a qualitative method to assess regional IMP uptake in the entire brain and to rate image data sets as normal or abnormal without knowledge of subjects'clinical classification. The sensitivity and specificity of IMP with single photon emission computed tomography in AD were 88% and 87%, respectively. In 15 patients with mild cognitive deficits (Blessed Dementia Scale score, less than or equal to 10), sensitivity was 80%. With the use of a semiquantitative measure of regional cortical IMP uptake, the parietal lobes were the most functionally impaired in AD and the most strongly associated with the patients' Blessed Dementia Scale scores. These results indicated that IMP with single photon emission computed tomography may be a useful adjunct in the clinical diagnosis of AD in early, mild disease.

Penetrating head injury in young adulthood exacerbates cognitive decline in later years.

Few investigators have studied whether the behavioral effects of brain insult in adulthood are stable after the period of maximum recovery. We addressed this issue in a 30-year longitudinal study of 84 veterans of World War II, 57 with penetrating head injury (HI) and 27 with peripheral nerve injury (PNI), matched with respect to age, premorbid intelligence, and premorbid education. Each subject was examined during the 1950s and during the 1980s; each examination included the largely verbal Army General Classification Test (AGCT) (with Vocabulary, Arithmetic, and Block Counting subscales) and the Hidden Figures Test (which measures figure-ground discrimination). HI exacerbated decline in performance over time, irrespective of lesion site or cognitive test. HI and PNI subjects differed significantly (p less than 0.05) in AGCT Total and Arithmetic change scores, and means were in the same direction for all other measures. In analyses contrasting subjects in each of the eight lesion groups to PNI subjects, those with left parietal lobe injuries showed significantly greater decline from the 1950s to the 1980s on the Vocabulary and Arithmetic subscales of the AGCT, as did those with left temporal lobe injuries on the Arithmetic subscale, whereas subjects with right parietal lobe injuries showed significantly greater decline on the Hidden Figures Test. We hypothesize that the observed reduction of cognitive capacities late in life was due to some combination of HI in young adulthood, secondary effects of the injury occurring with time, effects of stress on remaining brain tissue caused by functioning for decades in a compromised state, and changes in the brain occurring with age. Although the HI subjects were not demented, follow-up studies must assess whether exacerbated decline is a harbinger of dementia.

Single photon emission computed tomography in Alzheimer's disease. Abnormal iofetamine I 123 uptake reflects dementia severity.

To determine whether abnormalities in regional cerebral functional activity estimated by iofetamine hydrochloride I 123 and single photon emission computed tomography can be detected in mild or moderate as well as severe cases of Alzheimer's disease (AD), we performed iofetamine I 123-single photon emission computed tomography in 37 patients with probable AD (nine patients with mild, 18 patients with moderate, and ten patients with severe dementia) and nine age-matched control subjects. Iofetamine I 123 uptake was measured in right and left frontal, temporal, parietal, and occipital cortices. Mean (right and left) iofetamine I 123 activity was lowest in the parietal region of patients with AD and was significantly reduced in the other three regions compared with control subjects. Only in the parietal region was lower relative iofetamine I 123 activity associated with an impaired level of patient function and with cognitive deficit.

Comparison of magnetic resonance and roentgen ray computed tomography in dementia.

To compare the merits of magnetic resonance imaging (MRI) and roentgen ray computed tomography (CT) in assessing patients with dementia, we examined pairs of MR and CT brain images obtained from 26 patients with Alzheimer's disease (AD), eight patients with vascular or mixed dementia, and two patients with Parkinson's disease plus dementia. Magnetic resonance and CT images were independently rated on a qualitative scale of 0 (normal) to 3 (severely abnormal) in 39 separate brain regions. Ratios of anterolateral and third ventricular linear spans to linear skull spans were measured. Abnormalities in subcortical white matter and in hippocampus, enlargement of basal and sylvian cisterns, and ventriculomegaly were more evident on MR than CT scans, but qualitative ratings in all other brain regions were similar. Linear ventricular span ratios based on MR images did not differ significantly from those measured on CT. White matter abnormalities on MR were high signal foci on T2-weighted images whose pathologic substrate was uncertain; in a single case studied pathologically, no abnormalities were detected in brain regions that contained high signal foci. Dementia severity correlated with periventricular white matter abnormalities on both MR and CT images.

Age at onset and rate of progression of Alzheimer's disease.

Age at onset, duration, and severity of dementia were evaluated in 165 patients with a clinical diagnosis of Alzheimer's disease. Rate of progression of dementia was determined in 77 patients by repeated administration of the Blessed Dementia Scale (BDS). The distribution of age at onset among patients was bimodal, with a division at about age 65. Duration of dementia at the time of initial examination was shorter, and rate of progression on follow-up examination was more rapid in senile-onset (age 65 or greater) than in presenile-onset (before age 65) cases. Considerable overlap among values for the two patient groups was observed for both variables, indicating that age at onset is not a strong predictor of rate of progression of dementia in patients with Alzheimer's disease.

Comparison of rates of progression in Alzheimer's disease and Parkinson's disease.

In order to compare the progression of memory impairments in Parkinson's disease (PD) and Alzheimer's disease (AD), we administered the Memory and Information section of the Blessed Dementia Scale (BDS) at least twice to 33 patients with PD and 70 with AD. The BDS scores of AD patients deteriorated over time. In contrast, the scores of PD patients were essentially stationary. A substantial difference in rate of cognitive decline persisted upon comparing only those PD and AD patients who showed memory deficits of the same magnitude. The uniform failure to observe cognitive deterioration among PD patients suggests that any PD patients who deteriorate at a rate typical of AD may indeed have AD or a related dementing disorder in addition to the characteristic nigral-striatal degeneration of PD.

Equivalent forms of the Boston Naming Test.

In order to develop a test of naming ability that is sensitive to changes in performance on repeated testing, but is unbiased by practice effects, the 85 items of the Boston Naming Test (BNT) were divided into two 42-item forms. Both forms were given to 15 healthy adult subjects, 24 patients with a clinical diagnosis of Alzheimer's disease, and 17 patients with other brain lesions. The reliability of the BNT was high as measured by coefficient alpha and interitem correlations. Performance on the two forms of the test was similar as indicated by mean scores and by correlations between scores. The BNT score includes uncued (spontaneous) and cued responses. When uncued responses were analyzed separately, the reliability and equivalence of the forms remained strong. Using uncued scores therefore does not alter the psychometric properties of the test, and considerably reduces administration time. The modification of the BNT described here should be useful in studies in which repeated measurements are obtained for the purpose of detecting changes in naming ability.

Piracetam combined with lecithin in the treatment of Alzheimer's disease.

Nootropics, a new class of drugs believed to activate mental functions, have been proposed as a treatment for clinical disorders in which cognition is impaired. We therefore administered the nootropic drug piracetam, alone and in combination with phosphatidylcholine (PC), to 18 patients with Alzheimer's disease (AD), and measured the effects of treatment on a broad range of cognitive functions. Piracetam was administered according to three double-blind crossover protocols and a replication study that differed in piracetam dose (2.4 to 9.9 g/day) and whether PC (18 g/day) was administered concurrently. The drug was well tolerated, and there were not toxic side effects. Plasma choline levels rose significantly during piracetam and PC administration; monoamine metabolites in cerebrospinal fluid were unaffected by treatment. Piracetam, either alone or in combination with PC, did not significantly affect cognition in the AD group as a whole, nor did it improve test performance in any single patient.

A stage analysis of self-initiated smoking reductions.

Most smoking cessation treatments are predicated on the assumption that the course of smoking reduction is psychologically homogeneous. The present study tested an alternative model incorporating three distinct stages: initial decision, initial control, and maintenance. Three measures (perceived health locus of control, desire to stop, and self-esteem) were used to predict self-initiated smoking reduction in 61 regular smokers. Criterion smoking change measures (one for each stage) were obtained at follow-up. Multiple regression analyses of the criteria showed a different set of predictors were significant for each: desire to stop predicted the decision to reduce smoking, self-esteem predicted initial smoking reduction, and the combination of internal health locus of control beliefs and strong desire to stop predicted successful maintenance of reduction. The differential success across criteria of the predictors shows the value of the stage analysis and suggests the development of smoking treatments varying by stage.

Measurement of smoking: surveys and some recommendations.

A survey of smoking cessation researchers found considerable disagreement in the measurement procedures used to determine treatment outcome. The survey investigated (1) the duration of the measurement interval used to determine abstinence and smoking rate; (2) procedures for classifying people who smoke after treatment but are abstinent at follow-up; and (3) procedures for classifying people who use marijuana or tobacco products other than cigarettes. The marked disagreement among researchers' survey responses was compounded by the failure of their published articles to explain how smoking had been measured and scored. The Discussion identifies long-term abstinence as the most critical problem; its measurement was least consistent procedurally across studies yet most important for comparing them. Recommendations are made for establishing measurement and reporting conventions.