Subcutaneous injection of diazoxide every 3 hr for a total of 5 doses in 15 hr produced a state of elevated drinking and antidiuresis in rats resulting in a massive, positive, self-imposed water load. Dilutional hyponatremia was present, but not serum hyposmolality, owing to the increased serum glucose and BUN. The mechanism by which diazoxide produces a polydipsia even in the presence of an accumulating water load may illuminate the genesis of other pathophysiological dilutional states.

Animals↗

PubMedDate not supplied

Schedule-induced ethanol dependence and phenobarbital preference.

Rats exposed to a daily 3-hr session of intermittent food delivery ingested physical-dependence-produced levels of 5% ethanol solution. Although this schedule induced a chronic, voluntary, daily overindulgence, this had no effect on 21-hr home-cage phenobarbital preference. The substitution of water for 5% ethanol during the daily 3-hr binge session did not change home-cage phenobarbital preference, which remained stable and similar to that of a control group of non-binging animals. This experiment and others indicate that physical dependence on ethanol does not play a major role in the maintenance of ethanol abuse or cross-abuse of the barbiturates.

Alcohol Drinking↗

PubMedDate not supplied

Ethanol polydipsic choice: effects of alternative fluid polydipsic history.

Two groups of rats drinking either 5% ethanol or 0.9% NaCl solution under a fixed-time 1-min schedule of food pellet delivery became polydipsic during daily 3-hr sessions. When both fluids were made available to animals during sessions, strong side preferences typically developed so that neither fluid was preferred in spite of the fact that one group had a mild-to-moderate physical dependence on ethanol. The group that drank 0.9% NaCl solution initially failed to acquire a strong 5% ethanol polydipsia when this became the sole available fluid, and special procedures were required to induce an ethanol polydipsia comparable to that of the other group. Hence, a history of 0.9% NaCl solution polydipsia interfered with the institution of chronic, ethanol overdrinking in this group. Equal ethanol intakes were maintained in the groups when a compound solution consisting of 5% ethanol plus 0.9% NaCl solution was available along with a 5% ethanol choice. Whenever a 0.9% NaCl solution was presented in competition with either 5% ethanol or the compound 5% ethanol plus 0.9% NaCl solution, ethanol intake was reduced. Implications for the prevention and amelioration of human ethanol overdrinking are discussed.

Alcohol Drinking↗

PubMedDate not supplied

Chronic alcohol dependence and water-electrolyte status.

Altered water-electrolyte status resulting from chronic alcohol dependence has been reported, although the nature of any such derangement is controversial. To illuminate this problem, four groups of rats were exposed chronically to schedule-induced polydipsia conditions with a single fluid available: 5% ethanol, 0.9% NaCl solution of 5% ethanol, 0.9% NaCl solution, or distilled water. An ad lib control group was also used. The water-electrolyte status of these groups was evaluated in two ways. First, the diuretic response to hydrochlorothiazide doses (8-12 mg/kg) was measured after 3.5 months of chronic polydipsia. Second, after approximately two additional months of polydipsia, extracellular fluid volume, as well as plasma volume and electrolytes were measured. Both alcohol-intake groups drank approximately 11.5 g ethanol/kg/day over the course of the experiment. Urinary volume response to the diuretic agent did not reveal that chronic ethanol led to either water retention or dehydration, even when extra NaCl intake was imposed chronically (NaCl-EtoH group). Animals that were overdrinking either water or the 0.9% NaCl solution had extracellular fluid volumes that were greater than the NaCl-EtOH-polydipsic group, but they were not significantly larger than ad lib controls. There were no significant differences with respect to serum electrolyte concentration measures among the groups. In conclusion, animals that drank ethanol chronically in a pattern known to produce physical dependence revealed no altered water-electrolyte status when evaluated by acute responses to a diuretic agent, a chronically-imposed extra NaCl load, or body fluid compartment and electrolyte concentration measures.

Alcohol Drinking↗

PubMedDate not supplied

Preference history prevents schedule-induced preferential ethanol acceptance.

Two groups of rats were given differential schedule-induced polydipsia histories. One had a history of choosing between 5% ethanol and 0.7% glucose solution (dilute, mildly acceptable), in daily, 3-hr, fixed-time 1-min schedules of food-pellet delivery, while the other similarly treated group chose between 5% ethanol and 5% glucose (highly acceptable). A 30-day period, wherein only 5% ethanol was available during daily sessions, intervened before session-fluid preferences were evaluated by pitting a series of glucose solutions of increasing concentration (0.7-5.0%) against 5% ethanol. The group which had a remote history of having chosen 5% glucose solution in preference to 5% ethanol imbibed less 5% ethanol during the series of glucose-ethanol acceptability preference tests. Hence, they were less vulnerable to a continuance of their ethanol overindulgence than the group with the remote history of having chosen 5% ethanol over the dilute glucose solution.

Alcohol Drinking↗

PubMedDate not supplied

Memory performance in healthy elderly without Alzheimer's disease: effects of time and apolipoprotein-E.

Transgenic mice expressing human APOE-epsilon4 develop an age-dependent decline in memory without pathological features of Alzheimer's disease (AD). This implicates APOE in the maintenance of memory during normal senescence, but parallel human studies are limited because longitudinal investigations of memory usually do not exclude patients with AD or "questionable" AD (QD). The current study examined the effect of APOE on cognitive function over time in elderly without dementia. We hypothesized that, compared to other APOE alleles memory decline even in healthy elderly would be greater among those with an APOE-epsilon4. The results of neuropsychological tests, grouped into domains of memory, language and visuospatial/cognitive function by factor analysis, were examined at three intervals over a seven-year period in 563 healthy elderly without AD or QD using generalized estimating equations. Memory performance declined over time, while scores on the visuospatial/cognitive and language factors did not change. Increased age was associated with lower scores, and higher education with higher scores on all factors at each interval. No APOE allele was associated with performance on a specific cognitive factor at any interval, but the presence of an APOE-epsilon4 allele was associated with a more rapid decline in the memory factor over the follow-up period. The effect was most pronounced among individuals with less than 10 years of formal education. There was no similar time-dependent relationship between APOE-epsilon4 and the language or visuospatial/cognitive factors. Transgenic mice and elderly humans without AD or QD expressing APOE-epsilon4 show a decline in memory performance over time. These observations provide evidence for an APOE-specific effect on memory during senescence.

Aged↗

PubMedDate not supplied

Schedule-induced chronic hypertension.

Rats were fed on an intermittent-feeding schedule one 45-mg food pellet every 90 sec for 5 hours per day (experimental group) or an equivalent food ration as a single, daily feeding (control group). All animals were mononephrectomized and given saline to drink. Experimental animals became polydipsic (schedule-induced polydipsia). The rate and amount of fluid intakes between the two groups were controlled in the second experiment. In both experiments a significant blood pressure difference developed between the groups and remained terminally after water replaced saline as the drinking fluid for about 3 weeks. The development of chronic hypertension in the experimental group in the second experiment is regarded as a psychosomatic counterpart of other excessive and persistent behaviors (e.g., polydipsia, aggression), which can be induced by certain intermittent-feeding schedules. Observations on the heart (increased weight), kidney (minor pathologic changes), and adrenals (no change) were consistent with essential hypertension.

Animals↗

PubMedDate not supplied

Sibling HLA-matched cord blood transplant for beta-thalassemia: report of two cases, expression of fetal hemoglobin, and review of the literature.

PURPOSE: A program of cord blood stem cell (CBSC) transplants for patients with beta-thalassemia major was initiated in conjunction with the prenatal diagnostic service in 1994. Two patients who received HLA-matched related CBSC transplants with posttransplant fetal hemoglobin (HbF) expression are described and the literature is reviewed. PATIENTS AND METHODS: After screening 12 pregnancies, matched sibling CBSC transplants were performed for 2 girls with beta-thalassemia major when they were 3.8 and 2.2 years old, respectively. Their HbF was assayed serially. RESULTS: The nucleated cell counts/kg were 11.4 x 10(7) and 6.2 x 10(7), which engrafted on days 19 and 24, respectively. The children are now transfusion-independent at 3 years and 1.2 years posttransplant. Their HbF levels showed a rapid rise posttransplant and reached peak levels of 37.2% and 42.2% on day 83 and day 88, respectively. The HbF levels declined to 1.0% and 3.8% on day 581 and day 305, respectively. Nine other sibling CBSC transplants for thalassemias have been reported with an engraftment rate of approximately 50%. Graft rejection was related to insufficient CBSC number in one. CONCLUSIONS: HbF levels in patients with beta-thalassemia major after CBSC transplants could be influenced by many factors, including reactivation of HbF synthesis, intrinsic rate of Hb switching of CBSC, and mixed chimerism.

Female↗

PubMedDate not supplied

Relationship between asthma prevalence and income among Canadians.

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Asthma↗

PubMedDate not supplied

Effect of HIV-1 infection on CD4 cells in a hemophilia cohort.

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Acquired Immunodeficiency Syndrome↗