Retrograde amnesia and the volume of critical brain structures.

There are many controversies concerning the structural basis of retrograde amnesia (RA). One view is that memories are held briefly within a medial temporal store ("hippocampal complex") before being "consolidated" or reorganised within temporal neocortex and/or networks more widely distributed within the cerebral cortex. An alternative view is that the medial temporal lobes are always involved in the storage and retrieval (reactivation) of autobiographical memories (multiple trace theory). The present study used quantitative magnetic resonance imaging (MRI) in 40 patients with focal pathology/volume loss in different sites, to examine the correlates of impairment on three different measures of RA. The findings supported the view that widespread neural networks are involved in the storage and retrieval of autobiographical and other remote memories. Brain volume measures in critical structures could account for 60% of variance on autobiographical memory measures (for incidents and facts) in diencephalic patients and for 60-68% of variance in patients with frontal lesions. Significant correlations with medial temporal lobe volume were found only in the diencephalic group, in whom they were thought to reflect thalamic changes, but not in patients with herpes encephalitis or hypoxia in whom the temporal lobes were particularly implicated. The latter finding fails to support one of the main predictions of multiple trace theory, as presently expounded.

Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk.

Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer.

Effects of past abuse experiences on children's eyewitness memory.

Relations between child maltreatment and children's eyewitness memory were examined. A matched sample of abused and nonabused 3- to 10-year-old children (n = 70) participated in a play session with an unfamiliar adult and were interviewed about the interaction 2 weeks later. Consistent with results from previous research, older compared to younger children's reports were more complete and accurate. Abused and nonabused children performed similarly with several exceptions: Nonabused children were more accurate in answering specific questions, made fewer errors in identifying the unfamiliar adult in a photo identification task, and (at least for younger boys) freely recalled more information. Most effects remained when group differences in IQ and behavioral symptomology were statistically controlled. Importantly, abused and nonabused children did not differ in their accuracy or suggestibility in response to questions that were relevant to abusive actions. Among abused children, however, those who suffered more severe sexual abuse made more omission errors to specific abuse-relevant questions. Contributions to psychological theory and legal implications for understanding children's eyewitness memory and testimony are discussed.

Effect of the interaction of parathyroid hormone and cyclosporine a on bone mineral metabolism in the rat.

Cyclosporine A (CsA) induces high turnover osteopenia in the rat and there is evidence for this in humans. Recent studies suggest that increases in parathyroid hormone (PTH) may be involved in posttransplantation bone loss. However, human studies are difficult to interpret since transplant patients usually receive a cocktail of immunosuppressants and have underlying disease. Our aim was to try to resolve the influence of the absence or presence of PTH on CsA-induced bone disease. Male Sprague Dawley rats aged 7-9 months, either sham operated or parathyroidectomized (PTX), were randomly divided into vehicle and CsA groups. All PTX rats were given oral calcium supplementation ad libitum. The rats were divided into groups: basal, sham/vehicle, sham/CsA, PTX/vehicle, and PTX/CsA. Serial biochemistry was performed 0, 14, and 28 days after the start of the experimental period; bone histomorphometry was performed 28 days after the start of the experimental period. Statistical analysis consisted of group comparisons and factorial analyses. The results showed that CsA alone produced a high turnover osteopenia consistent with previous studies. In the PTX animals there was an increase in bone mass. PTX also decreased osteoblast activity and recruitment, and serum 1,25OH2D levels. Serum levels of osteocalcin (BGP) were unaffected by PTX. The combination group (PTX/CsA) did not differ statistically from the controls in most of the histomorphometric parameters measured, with the exception of reduced mineral apposition and bone formation rates, reflecting the effects of PTX. Serum BGP and 1,25OH2D levels did not differ, but PTH was reduced from the control. Explanations for these results are (1) CsA and PTX exert their effects via separate mechanisms, negating each other; (2) in the absence of PTH, CsA managed to cause bone loss, and thus PTH may not be essential for CsA-induced bone loss; or (3) the profound accelerated bone loss produced by CsA in normal rats requires PTH. These findings may help explain the discrepancies found in clinical studies where bone loss occurs with either elevated or normal PTH levels.

Immunosuppressant use without bone loss--implications for bone loss after transplantation.

Cyclosporine A (CsA) is associated with posttransplantation bone disease. Immunosuppressant drugs such as sirolimus (SRL), which are more potent and less deleterious than CsA, are being developed. Previous experiments have shown that SRL although immunosuppressive, is relatively bone sparing. The use of low doses of CsA and SRL in combination has displayed in vivo synergism. This study was initiated to examine the effect of low-dose CsA and SRL on bone metabolism, thereby hopefully providing a bone sparing immunosuppressive regimen for transplant recipients. One hundred and nineteen rats were divided into groups: basal, vehicle, CsA high dose, CsA low dose, SRL low dose, and combination low-dose CsA and SRL. The basal group was killed on day 0 for histomorphometry. The experimental groups were weighed and bled on days 0, 28, 56, and 84 and were killed on day 84 for histomorphometry. Serial assays for blood urea nitrogen (BUN), creatinine, and osteocalcin were performed. Osteocalcin was raised on days 28 and 56 in the high dose CsA group. Histomorphometry showed osteopenia with high-dose CsA. Low-dose CsA was relatively bone sparing, while low-dose SRL and combined low-dose CsA did not cause bone loss. In conclusion, the synergistic combination of low-dose CsA and SRL has the potential of providing both bone sparing and immunosuppressive benefits.

Using water sprays to improve performance of a flooded-bed dust scrubber.

Supplemental water sprays were placed along the sides of a continuous mining machine to improve suppression and confinement of the dust cloud under the cutting boom to reduce downwind dust levels. Using a full-scale mock-up of a continuous mining machine, preliminary work showed that these side sprays improved suppression of the dust cloud and redistributed this cloud under the cutting head. This led to reductions in dust levels around the machine and in down-wind airways for some positions of the mining machine. This testing also showed that side spray effectiveness was influenced by the distance from the fresh air ventilation device to the cutting surface, termed the ventilation setback distance. These sprays produced larger reductions in machine and return dust levels at smaller setback distances than at larger setback distances. These side sprays then were installed in similar locations on a mining machine at an underground coal mine operation to evaluate their effectiveness for improving suppression and capture of dust by the flooded-bed dust scrubber. Although sampling could not be conducted successfully in the return, sampling around the mining machine and at the machine operator showed that dust levels decreased with use of these sprays. Further analysis showed that these sprays were most effective at the smaller setback distances, a result confirmed by full-scale laboratory testing.

Prevention of lung cancer.

Lung cancer is the major cause of death in industrialized western societies. Its link to tobacco abuse is well established and efforts should be made to eliminate this potent environmental carcinogen. The concept of chemoprevention, the use of agents to inhibit and reverse lung cancer carcinogenesis, has great appeal. The CARET study, conducted in 18,000 high-risk smokers in the US, found that a combination of beta-carotene and retinyl palmitate resulted in a 28% increase in the incidence of lung cancer. A similar study conducted in Finland, the ATBC trial utilizing alpha tocopherol and beta-carotene, had similar findings for the group taking beta-carotene. These two trials have caused a rethinking of the use of natural compounds as chemoprevention agents. These agents should no longer be regarded as harmless, but as having potential toxicities. A new approach in the chemoprevention of cancer has been the concept of surrogate endpoints, biological changes that are on the pathway to cancer. Trials are underway to determine what are appropriate surrogate endpoints for lung cancer chemoprevention trials.

Interferon-alpha, unlike interferon-gamma, does not cause bone loss in the rat.

Interferons (IFN) are a group of related glycoproteins. IFN-gamma, in vitro, has been shown to inhibit resorption; however, an in vivo experiment showed that it had the opposite effect, resulting in bone loss that was comparable to that caused by cyclosporine A. IFN-alpha has numerous clinical applications but is used most extensively in the treatment of chronic hepatitis B and chronic hepatitis C. Research into the effects of IFN-alpha on bone mineral metabolism has been very sparse, and the majority of studies reflect in vitro models. Like IFN-gamma, there exists discordance between in vitro and in vivo studies on IFN-alpha. Both in vivo and in vitro studies demonstrate that IFN-alpha decreases bone resorption, whereas osteoblasts may or may not be affected in vivo. This study was designed to provide information on the in vivo effects of IFN-alpha in the rat model, because we feel that, given its widespread clinical use, this is an extremely important issue. Rats were given low dose IFN-alpha (1.6 x 10(6) IU/m2), intermediate dose IFN-alpha (5.35 x 10(6) IU/m2), and high dose IFN-alpha (30 x 10(6) IU/m2) three times per week for 28 days. Serum osteocalcin (bone gla protein, or BGP) and parathyroid hormone (PTH) were measured serially and, after double labeling, the bones were examined histomorphometrically. IFN-alpha did not alter any of the histomorphometric parameters measured and did not affect PTH. However, it produced a disparate BGP response. Low dose IFN-alpha resulted in a statistically significant increase in serum BGP on days 14 and 28, whereas intermediate and high doses of IFN-alpha did not. Overall, these results provide no evidence of a deleterious effect of IFN-alpha on bone metabolism and confirm the limited clinical study.

Emotion and memory: Children's long-term remembering, forgetting, and suggestibility.

Children's memories for an experienced and a never-experienced medical procedure were examined. Three- to 13-year-olds were questioned about a voiding cystourethrogram fluoroscopy (VCUG) they endured between 2 and 6 years of age. Children 4 years or older at VCUG were more accurate than children younger than 4 at VCUG. Longer delays were associated with providing fewer units of correct information but not with more inaccuracies. Parental avoidant attachment style was related to increased errors in children's VCUG memory. Children were more likely to assent to the false medical procedure when it was alluded to briefly than when described in detail, and false assents were related to fewer "do-not-know" responses about the VCUG. Results have implications for childhood amnesia, stress and memory, individual differences, and eyewitness testimony.

Trauma, memory, and suggestibility in children.

In this review we examine factors hypothesized to affect children's memory for traumatic events. Theoretical ideas on the processing and remembering of trauma are presented and critiqued. We review research on how psychopathology may generally influence and dissociation and posttraumatic stress disorder may specifically influence children's memory and suggestibility. The special case of child maltreatment is addressed as it relates to interviewing children about traumatic life experiences. Throughout we draw on current developmental, cognitive, social, and clinical theory and research. The review covers a controversial and exciting area of psychological inquiry.

The association between participant characteristics and serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol among participants in the Carotene and Retinol Efficacy Trial (CARET) for prevention of lung cancer.

As part of the multicenter Carotene and Retinol Efficacy Trial (CARET) lung cancer prevention study, we investigated the associations of baseline demographic, health history, and nutritional intake information and the prerandomization serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol in a random subset of 1182 smokers and asbestos-exposed workers. Dietary intake was estimated via a self-administered food frequency questionnaire using the recently updated United States Department of Agriculture/National Cancer Institute database. In multiple regression analyses, supplemental vitamin use was the strongest predictor of each of the four analytes. There was a statistically significant inverse relationship between smoking and beta-carotene concentrations. Lower serum beta-carotene was associated with current smoking, higher daily cigarettes smoked, and more pack-years. Serum beta-carotene concentrations were higher with increasing years since stopping cigarette use, which suggests a biological mechanism for the lower serum concentration of beta-carotene in smokers. We found weak inverse associations between alcohol intake and the serum concentrations of both beta-carotene and retinol. As in previous reports, dietary intakes as measured by a food frequency questionnaire can only moderately predict serum concentrations of beta-carotene, retinol, retinyl palmitate, and alpha-tocopherol.

Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.

BACKGROUND: Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. RESULTS: A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

Psychological science and the use of anatomically detailed dolls in child sexual-abuse assessments.

Many devices are used in child assessment and treatment as communication aids, projective tools, and symbolic means of interaction. None are as hotly debated in their application among mental health professionals as dolls with genital details. Anatomically detailed (AD) dolls are often used in sexual-abuse evaluation and treatment with children, but such applications are controversial. This article is the product of a working group formed to review AD doll research and practice. This article reviews historical use of dolls in clinical inquiry and research on sexual behaviors in children, normative use of AD dolls in nonreferred children, differences in children's play behavior and emotional reactions to AD dolls, and memory and suggestibility issues relating to AD-doll use. Recommendations for future research are provided.

Dermabrasion using tumescent anesthesia.

BACKGROUND: Dermabrasion is a very useful and versatile technique. However, it suffers from side effects and difficulties that limit its popularity among operating dermatologic surgeons and the public. OBJECTIVE: To show that it is possible to eliminate the need for chlorofluorocarbons, improve the standard dermabrasion technique, decrease the healing time, improve its side effect profile, and reduce risks to the operating surgeon. METHODS: Tumescent fluid containing dilute Xylocaine, bicarbonate, and epinephrine in saline was infiltrated before coarse wire brush dermabrasion. Eutectic mixture of local anesthetic (EMLA) was also used topically. The first 14 patients dermabraded by this method are reported on here. Their healing, progress, side effects, and results are described. A patient questionnaire was completed by 12 of the patients who describe the procedure and results from the patient's viewpoint. RESULTS: The procedure was found to be effective in producing anesthesia, eliminating the use of freezing the skin, and limiting the necessity for sedatives, narcotics, and other anesthesia. It gives a firm surface to dermabrade against, makes the procedure more rapid and technically easier, and produces less splatter and therefore less risk for the surgeon. The results subjectively and objectively would appear to be at least as good as standard techniques. The healing in this small sample would appear to be faster both to reepithelialization and to reestablishment of normal color. There was only one case of transient hyperpigmentation lasting less than 1 week. Otherwise there were no cases of pigmentary or scarring side effects. CONCLUSION: Tumescent dermabrasion is safe, effective, and has many benefits over traditional methods.

The effect of long-term beta-carotene and vitamin A administration on serum concentrations of alpha-tocopherol.

Many micronutrients are currently being tested for cancer prevention activity. A short-term study recently suggested that two of these nutrients, beta-carotene and alpha-tocopherol, may have an adverse interaction, with beta-carotene supplementation leading to markedly decreased serum concentrations of alpha-tocopherol. We have analyzed the effect of beta-carotene supplementation on serum concentrations of alpha-tocopherol in 2319 participants enrolled in the Carotene and Retinol Efficacy Trial who have taken beta-carotene and vitamin A for up to 6 years. One thousand thirty-five participants enrolled in two pilot trials to the Carotene and Retinol Efficacy Trial had serum collected at yearly intervals; an additional 1284 recently recruited participants had serum collected at biennial intervals. Using standard high pressure liquid chromatography techniques, with attention to quality control, these samples were analyzed for beta-carotene and alpha-tocopherol. After up to 6 years of supplementation with beta-carotene (30 mg/day) and vitamin A (25,000 international units/day) we found a small but statistically significant increase in the serum concentration of alpha-tocopherol in participants taking the active agents. No evidence of a decrease was found in any of the subpopulations examined. We conclude that long-term supplementation with the combination of beta-carotene and vitamin A does not decrease serum concentrations of alpha-tocopherol. Our long-term trial validates results from several shorter trials conducted by others. The concept of adverse interactions between supplemental micronutrients is important. All cancer prevention trials should closely monitor serum concentrations of micronutrients, as well as the incidence of other significant disease.

The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

The Carotene and Retinol Efficacy Trial (CARET) to prevent lung cancer in high-risk populations: pilot study with cigarette smokers.

In preparation for a phase IV lung cancer chemoprevention trial, we conducted a pilot trial of beta-carotene and retinol in high-risk smokers. Eligibility criteria were ages of 50-69 years, a smoking history of at least 20 pack-years, and either being a current smoker or having quit within the past 6 years. Participants were recruited by mailing an interest survey to 29,928 age-selected members of King County Medical Blue Shield. We randomized 1,029 women and men to one of four intervention arms: placebo, retinol, 25,000 international units/day; beta-carotene, 30 mg/day; or retinol plus beta-carotene. Participants were followed for side effects and adherence every 2 months either by a telephone call or a clinic visit. Blood was sampled for retinoid, carotenoid, and liver function analyses annually. beta-carotene and retinol were well tolerated during the follow-up period, which had a median of 1.5 years and a maximum of 3.3 years. Yellowing of the skin was seen in both beta-carotene arms. No differences were seen among arms or over time in incidence or severity of the other 15 monitored symptoms and signs or in serum liver function tests. Adherence was good: 83% of participants remained active on study at 1 year and 75% at 2 years. Serum beta-carotene increased from a prerandomization median concentration of 170 to 2100 ng/ml after 4 months of supplementation, and retinyl palmitate median levels more than tripled.(ABSTRACT TRUNCATED AT 250 WORDS)

Children's eyewitness memory: effects of participation and forensic context.

We examined effects of participation and forensic context on 4-year-old children's testimony. Children in "participant" and "police" conditions actively participated in games with a "babysitter"; each child in the "observer" condition watched a videotape of a child and the babysitter playing. Eleven days later, children were individually questioned about the event. Before the interview began, children in the police condition talked to a police officer who said the babysitter might have done something bad. Comparison of participant- and observer-condition performance indicated that participation increased free-recall accuracy concerning actions that took place and lowered suggestibility. Comparison of participant- and police-condition performance indicated that forensic context led to increased error in free recall and additional comments to misleading questions. However, forensic context also resulted in higher accuracy on an age-identification task and did not affect children's accuracy in answering abuse-related questions.

Association of food frequency questionnaire estimates of vitamin A intake with serum vitamin A levels.

To assess the validity of nutrient intake estimates from a food frequency questionnaire, the authors compared estimates of intake of preformed retinol (dietary plus supplements), beta-carotene, other active carotenoids, and total vitamin A computed from questionnaire responses with serum retinoid and carotenoid concentrations. Data were obtained from 302 male and female current or former smokers, participants in a lung cancer chemoprevention trial at the Fred Hutchinson Cancer Research Center in Seattle, Washington, during 1985-1986. Both serum beta-carotene and serum alpha-carotene were associated, although weakly, with food frequency estimates of total vitamin A intake, dietary vitamin A, beta-carotene, other carotenoids, and total carotenoids (0.18 less than or equal to r less than or equal to 0.26). Serum retinol was associated with supplementary vitamin A intake (r = 0.16). Nondietary factors were also associated with serum nutrient concentrations--in particular, cigarette smoking, alcohol intake, and body mass index. Cigarette smoking emerged as an important modifying factor of the relation between serum beta-carotene and dietary beta-carotene (r = 0.14 for current smokers, r = 0.30 for former smokers).