Severity of cognitive impairment in Alzheimer's disease affects list learning using the California Verbal Learning Test (CVLT)

Impairment in list learning is considered a primary symptom of Alzheimer's disease (AD), yet there are no published reports examining the relationship between list learning and severity of cognitive impairment. We gave nine-item and 16-item versions of the California Verbal Learning Test (CVLT; Delis et al., 1987), a standardized shopping list assessment of memory, to 24 AD patients (mean age = 76.2 +/- 8.1; mean years of education = 13.8 +/- 2.4), who were stratified into four groups based on MMSE scores (mean = 16.0 +/- 5.6). ANOVAs revealed severity effects for total list learning (p < 0.001), the first trial (p < 0.001), the last trial (p < 0.001) and short- and long-delay recall measures. Most of these differences seemed due to floor effects. For example, the modal number of words recalled after a delay was 0 by subjects with MMSE scores below 21. Severity of cognitive impairment was associated with the proportion of intrusions such that the most severely demented subjects gave almost entirely intrusion responses. Surprisingly, list length did not significantly affect any of the free recall measures. Our results suggest that list learning and recall seem to be lost relatively early in AD. Measures of list recall like the CVLT may not be useful in tracking severity of cognitive impairment over time.     

Associative and nonassociative tolerance: the effects of dose and interdose interval

Two experiments examined the effects of dose and interdose interval (IDI) on associative and nonassociative tolerance to morphine analgesia in rats. Associative contingencies were manipulated by administering low (5 mg/kg) or high (20 mg/kg) doses of morphine explicitly paired or unpaired with a distinctive context. Nonassociative processes were manipulated by administering morphine at a short (6-h) or long (96-h) IDI. Tolerance was assessed as shifts in morphine dose-response curves on the tail-flick test. Animals in the long IDI conditions showed considerable context-specific tolerance. Tolerance in the short IDI conditions was not influenced by contextual contingencies at the immediate test (Experiment 1) and showed no retention over a 30-day interval (Experiment 2), suggesting this tolerance was nonassociative. The impact of massed exposure to morphine and context on the disruption of learning at the short IDI is discussed.     

Mycobacteremia in patients with the acquired immunodeficiency syndrome

BACKGROUND: Bacillemia is a key event in the pathogenesis of tuberculosis. Although current evidence indicates that Mycobacterium tuberculosis bacteremia is rare in patients seronegative for the human immunodeficiency virus, it has been increasingly reported in patients with the acquired immunodeficiency syndrome (AIDS). OBJECTIVE: To determine clinical and laboratory characteristics of patients with AIDS and tuberculosis with and without bacillemia. METHODS: Fifty patients with AIDS with clinical suspicion of disseminated mycobacterial disease were prospectively selected. Three consecutive blood samples were collected for culture using a standardized protocol. RESULTS: Mycobacterium was isolated from any body site in 42 patients (84%). Bacillemia was detected in 30 (71.4%) of these 42 patients: 11 (28.2%) caused by Mycobacterium avium-intracellulare complex and 19 (71.8%) caused by M tuberculosis. Blood culture was the only method used to confirm the diagnosis in 5 (15%) of the 33 tuberculosis cases. Tuberculosis in patients with AIDS developed with nonspecific insidious symptoms, a remarkable elevated alkaline phosphatase level, and without the classic miliary radiological pattern. We could demonstrate 2 previously unrevealed clinical characteristics of bacteremic tuberculosis in patients with AIDS: a shift to the left in the white blood cell count and abdominal lymph node enlargement. In patients with tuberculosis, the in-hospital mortality rate was higher among patients with bacillemia, although the posttreatment survival rate was comparable. CONCLUSIONS: Blood culture is a valuable tool to confirm the clinical diagnosis of disseminated tuberculosis in patients with AIDS and can distinguish patients with characteristic clinical findings and outcome. Abdominal ultrasonography may be an additional helpful tool to identify these patients.     

In vitro functional properties of the rat bladder regenerated by the bladder acellular matrix graft

PURPOSE: To assess the response of rat urinary bladder regenerated by the homologous bladder acellular matrix graft (BAMG) to in vitro electrical and pharmacologic stimuli. MATERIALS AND METHODS: In Sprague-Dawley rats, partial cystectomy (>50%) was performed, followed by BAMG augmentation cystoplasty. After 4 months, organ bath studies of tissue strips in 10 were used to compare the contractility of the BAMG regenerates and the corresponding host detrusor smooth muscle. RESULTS: The BAMG regenerates exhibited contractile activity to electrical field stimulation and a qualitatively identical pattern of response to muscarinic, purinergic, alpha- and beta-adrenergic drug administration and nitric oxide. At 4 months after surgery, the maximum forces of contraction of the BAMG regenerates to carbachol stimulation amounted to close to 80% of the host bladder response. With electrical field stimulation, they equaled 44% and 62% of the host bladder response after 2.5 and 4 months, respectively. Histological and immunohistochemical studies confirmed the presence of receptors for neurotransmitters that these functional in vitro studies implied. CONCLUSIONS: The present study provides further evidence that augmentation cystoplasty with the BAMG leads to functional regeneration of the rat bladder detrusor smooth muscle.     

Determination of fluoxetine and norfluoxetine concentrations in cadaveric allograft skin

Fluoxetine hydrochloride is the sixth most prescribed drug in the United States and is administered to treat major depression. A cadaveric skin donation was obtained from a 46-year-old woman who died as a result of a fluoxetine overdose. Due to the potential penetration of the drug and its major metabolite, norfluoxetine, into skin, the safety of using the skin as an allograft was questioned. Our evaluation showed that mean concentrations in skin were 2304+/-175 and 1353+/-102 ng/g of skin, respectively. The skin:plasma ratio was 0.41. Clinically, the amount of fluoxetine that can be transferred to an allograft recipient depends on many factors. Based on penetration of drug and metabolite into skin, one would have to evaluate carefully the risk:benefit ratio of using allografts from a donor who died from a fluoxetine overdose.     

Ionotropic glutamate receptor subtypes activate c-fos transcription by distinct calcium-requiring intracellular signaling pathways

In this study the effects of angiotensin II (AII) angiotensin II hexapeptide [AII(1-6)] and angiotensin II pentapeptide [AII(2-6)] on the motility, stereotypy, learning of conditioned avoidance responses (CARs) and recall of a passive behavior making it possible to avoid aversive stimulation in rats, were compared. All the peptides were injected into the lateral cerebral ventricle (icv) in a dose of 1 nmol. AII caused a statistically significant increase in the number of crossings, rearings, and bar approaches in an open field whereas [AII(1-6)] and [AII(2-6)] were inactive in this test. The stereotypic behavior induced by an intraperitoneal (ip) injection of apomorphine (1 mg/kg) and amphetamine (7.5 mg/kg) was statistically significantly enhanced only in the rats which received AII icv. The application of AII, but not that of [AII(1-6)] and [AII(2-6)] resulted in a quicker acquisition of the CARs. A better recall of passive avoidance was achieved only by AII, while the fragments [AII(1-6)] and [AII(2-6)] had no effect. These findings indicate that the 1-6 and 2-6 fragments of AII do not possess a psychotropic activity like that of the parent octapeptide.     

Does alpha-melanocyte-stimulating hormone from the pars intermedia regulate suckling-induced prolactin release? Supportive evidence from morphological and functional studies

Recent evidence suggests that substances derived from the hypophyseal intermediate lobe (IL) play a crucial role in the regulation of suckling-induced PRL secretion. The purpose of the present study was to explore this possibility further by determining whether the suckling stimulus acutely increases the secretory activity of the IL and whether alpha MSH, a major secretory product of the IL, plays a specific role in suckling-induced PRL release. Light microscopic morphometric analysis of serial pituitary sections obtained from lactating rats revealed that as little as 1 min of suckling caused a significant increase in the proportion of the IL that was in secretory configuration (11.8 +/- 0.7% vs. 6.7 +/- 0.5%; 1-min suckled vs. nonsuckled control; mean +/- SE). Moreover, the fraction of the IL in secretory configuration continued to increase after 5 and 10 min of nursing (to 16.0 +/- 0.8% at 5 min and 18.2 +/- 0.7% at 10 min). In contrast, serum PRL was not significantly elevated above the control level after 1 min of suckling (18.1 +/- 13.5 vs. 9.9 +/- 6.5 ng/ml, 1-min suckled vs. control). In fact, a significant rise in PRL levels (to 314.4 +/- 19.4 ng/ml) could be detected only after 10 min of nursing. Thus, secretion by the IL in response to suckling preceded the release of adenohypophyseal PRL, suggesting that a secretory product(s) from the pars intermedia is involved in the modulation of nursing-induced PRL release. Having established a sequential temporal relationship between these two phenomena, we next investigated whether alpha MSH was the IL factor involved in the regulation of suckling-induced PRL secretion. To this end, lactating rats were injected either with antiserum to alpha MSH or preimmune serum and then allowed to nurse their pups. Serial blood samples were taken from the mothers 15, 30, 60, and 90 min after the litters were returned, and serum PRL was measured by RIA. We found that the suckling-induced rise in serum PRL was severely attenuated in animals that received anti-alpha MSH serum. This suppression was most evident at 15 min (70.1 +/- 13.4 vs. 323.5 +/- 127.0 ng/ml, antibody treated vs. preimmune serum control) and persisted throughout the entire 90-min test period. When taken together, our results suggest that suckling-induced PRL secretion is mediated at least in part by alpha MSH released from the hypophyseal IL.