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We have demonstrated that RRR-alpha-tocopheryl succinate (10 microg/mL vitamin E succinate (VES) treatment of estrogen receptor-negative MDA-MB-435 human breast cancer cells induces 9, 19, 51, and 72% apoptotic cells on days 1-4, respectively, after treatment, which involves transforming growth factor-beta signaling. Here, we show that VES-triggered apoptosis of MDA-MB-435 cells induced prolonged elevated expression of c-jun mRNA and protein (neither of which was caused by major increases in stability) and also induced enhanced activator protein-1 (AP-1) binding to the consensus DNA oligomer. Furthermore, VES treatments resulted in increased AP-1 transactivation activity, as measured with an AP-1 promoter/luciferase reporter construct and by the measurement of increased mRNA expression of the AP-1-dependent endogenous gene collagenase. Evidence of VES-induced involvement of the c-jun amino-terminal kinase in these AP-1-dependent events was suggested by data showing prolonged activity of this kinase, as measured by a kinase assay using glutathione S-transferase-c-jun as the substrate. The c-jun-dependent transcriptional activity was verified by cotransfection of a chimeric transcription factor having a galactose 4 DNA-binding domain coupled with the transactivation domain of c-jun plus the reporter plasmid 5X GAL4-luciferase. MDA-MB-435 cells infected with an adenovirus expression vector containing the TAM-67 sequence for dominant/negative-acting mutant c-jun or transiently transfected with c-jun antisense exhibited a 50-77% reduction in VES-mediated apoptosis as compared with control adenovirus-infected or control sense oligomer-transfected cells.

This study examined the effects of arginine supplement of fluid resuscitation from burn injury on cardiac contractile performance and bacterial translocation after a third-degree burn comprising 43% of the total body surface area in adult rats. Before burn injury, rats were instrumented to measure blood pressure; after burn (or sham injury), paired groups of sham-burned and burned rats were given vehicle (saline), L-arginine, D-arginine, or N-methyl-L-arginine (300 mg/kg in 0.3 ml of saline 30 min, 6 h, and 23 h postburn) plus fluid resuscitation; sham-burned rats received drug only. Twenty-four hours after burn trauma, hemodynamics were measured; the animals were then killed and randomly assigned to Langendorff heart studies or to studies examining translocation of gut bacteria. Burn rats treated with vehicle, D-arginine, or N-methyl-L-arginine had well-defined cardiocirculatory responses that included hypotension, tachycardia, respiratory compensation for metabolic acidosis, hypocalcemia, cardiac contractile depression, and significant bacterial translocation. Compared with values measured in vehicle-treated burn rats, L-arginine given after burn improved blood pressure, prevented tachycardia, reduced serum lactate levels, improved cardiac performance, and significantly reduced bacteria translocation, confirming that L-arginine administration after burn injury provided significant cardiac and gastrointestinal protection. Circulating neutrophil counts fell after burn trauma and serum glucagon levels rose, but these changes were not altered by pharmacological intervention. Our finding of significantly higher coronary perfusate guanosine 3',5'-cyclic monophosphate concentration in L-arginine-treated burn rats suggests that the beneficial effects of L-arginine were mediated by nitric oxide production.

This study evaluated the effect of preoperative sleep on the success of conscious sedation. Seventy-six children, from 18 to 61 months of age, participated in this study. Sixty-two children received chloral hydrate (50-60 mg/kg) and hydroxyzine (15-35 mg) and 14 children received intramuscular meperidine hydrochloride (2.2 mg/kg). Parents were asked to complete a questionnaire which asked several questions about their child's activity the previous day, and their bedtime. The operator ranked the sedations on a scale of 1 to 4, with 1 being good and 4 being poor. The results were statistically evaluated using the Wilcoxon Rank sum test. The children that received a normal amount or greater amount of sleep preoperatively did not show any significantly higher degree of success (p < 0.26) with their sedation appointment. The parents' perception of their child's tiredness did demonstrate borderline (p < 0.08) significance. Children greater than 36 months of age had a significantly higher (p < 0.03) degree of successful sedations. The results of this study demonstrated that there was no clear correlation between the child's preoperative sleep and the outcome of the sedation, but that a tired child may increase the likelihood of a poor sedation. In addition, the child's age at the time of the sedation may affect the outcome of the sedation.

Activation of the amygdala in rats produces cardiovascular changes that include increases in heart rate and arterial pressure as well as behavioral changes characteristic of emotional arousal. The objective of the present study was to examine the interaction of GABA and excitatory amino acid (EAA) receptors in the basolateral amygdala (BLA) in regulating cardiovascular function. Microinjection of the GABAA receptor antagonist bicuculline methiodide (BMI) or the E A A receptor agonists NMDA or AMPA into the same region of the BLA of conscious rats produced dose-related increases in heart rate and arterial pressure. Injection of the nonselective EAA receptor antagonist kynurenic acid into the BLA prevented or reversed the cardiovascular changes caused by local injection of BMI or the noncompetitive GABA antagonist picrotoxin. Conversely, local pretreatment with the glutamate reuptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid enhanced the effects of intra-amygdalar injection of BMI. The cardiovascular effects of BMI were also attenuated by injection of either the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) or the AMPA receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX). When these two EAA receptor antagonists were combined, their ability to suppress BMI-induced tachycardic and pressor responses was additive. These findings indicate that the cardiovascular effects caused by blockade of GABAergic inhibition in the BLA of the rat are dependent on activation of local NMDA and AMPA receptors.

Study Objectives: To evaluate the safety and efficacy of thermal balloon endometrial ablation in women with menorrhagia, and to identify factors influencing outcome., Design: Prospective, observational study (Canadian Task Force classification II-2)., Setting: Three Canadian university-affiliated teaching hospitals., Patients: One hundred twenty-one women suffering from menorrhagia serious enough to make them candidates for endometrial ablation or hysterectomy. Patients without obvious structural or (pre)malignant abnormalities were included if their uterine cavities sounded to less than 12 cm, they were in good health, and had undergone hysteroscopy or pelvic ultrasound and endometrial biopsy within 6 months and had a normal Papanicolaou smear within 1 year., Interventions: A balloon catheter was placed through the cervix and after inflation in the endometrial cavity with 5% dextrose in water, was heated to 87 +/- 5 degrees C. Two-thirds of patients avoided general anesthesia and very few required cervical dilatation to admit the 4.5-mm diameter catheter. Balloon pressures were 90 to 140 mm Hg in 13 patients; pressures between 140 and 190 mm Hg were well tolerated by the rest. Nineteen women underwent 12 minutes of therapy, and the rest had 8-minute sessions., Measurements and Main Results: No intraoperative complications occurred, and minor postoperative morbidity occurred in 4% of patients. Preoperative and postoperative bleeding was assessed by pad counts and patient self-reports. The degree of dysmenorrhea was recorded similarly. A paired t test was used to compare pretreatment with posttreatment pad counts. A Wilcoxon signed rank test was employed to evaluate the effect of treatment on dysmenorrhea. The effects on outcome of several independent variables were analyzed by multiple and logistic regression. Success of the procedure was constant over the year (range 86-90%). Treatment led to significant decreases in menstrual flow, duration, and pain (p <0.0001). No significant effects of parity, uterine position or cavity depth, timing, or various endometrial-thinning regimens were found. Increasing age was significantly associated with increased odds of success (p < 0.05). Excluding the 19 women who underwent 12 minutes of therapy did not change statistical results, whereas excluding the 13 treated with balloon pressures less than 140 mm Hg improved the results. Conclusion. The facts that bleeding and dysmenorrhea were significantly reduced by thermal balloon endometrial ablation, that no intraoperative complication occurred, and that postoperative morbidity was minimal, lead us to conclude that this is potentially a safe and effective technique. Larger studies and longer follow-up are required to substantiate this impression.

Previous studies have shown that treatment of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells with 10 microg/ml (18.8 microM) of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for 3 days induced approximately 50% of the cells to undergo apoptosis. Elevated and prolonged expression of c-jun mRNA and protein was temporally correlated with VES-induced cell death. Data presented in this paper show that the elevated and prolonged expression of c-jun message and protein are not accounted for by enhanced stability, and show the involvement of c-Jun in VES-induced apoptosis in this lymphoblastoid cell type. C4-1 cells infected with a virus carrying a dominant, negatively acting mutant form of c-Jun, supjun-1, exhibited: (i) 71% reduction in VES-induced apoptosis, (ii) a 2.0-2.5-fold decrease in wildtype, endogenous c-Jun expression, and (iii) a 2.4-2.6-fold reduction in AP-1 binding activity. Additionally, cells co-treated with VES plus RRR-alpha-tocopherol, exhibited a 70% reduction in apoptosis, a marked reduction in c-Jun expression and a 1.6-fold reduction in AP-1 binding activity. These studies suggest that c-Jun plays a crucial role in VES-induced apoptosis in C4-1 cells, and add to our understanding of mechanisms of action involved in VES-mediated tumor cell growth inhibition.

The purpose of this study was to document induction of apoptosis by vitamin E succinate (VES; RRR-alpha-tocopheryl succinate) in human breast cancer cells in culture and to characterize potential c-jun involvement. VES at 18.8 microM (10 micrograms/mL) induced DNA synthesis arrest, reduced total cell numbers, and induced apoptosis in estrogen receptor-positive and estrogen-responsive MCF-7 human breast cancer cells. VES at 10 micrograms/mL induced apoptosis in greater than 60% of cells within 3 d of treatment. Apoptosis was documented by detection of fragmented or condensed nuclei in 4',6-diamindino-2-phenylindole-stained cells, detection of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeled DNA, and DNA laddering. Analyses of mRNA and protein levels of candidate molecules involved in apoptosis showed that MCF-7 cells treated with VES exhibited elevated and persistent expression of c-jun. MCF-7 cells stably transfected with a dominant-negative interfering mutant c-jun, TAM-67, and expressing high levels of mutant jun exhibited approximately 50% blockage of VES-mediated apoptosis. In addition to increased c-jun expression after VES treatment, VES-treated MCF-7 cells exhibited elevated activator protein-1 (AP-1) binding activity. Comparisons of AP-1 binding factors by super-shift analyses with jun-specific antibodies in cells sensitive to VES-induced apoptosis (empty-vector control 7-1 cells) and cells resistant to VES-induced apoptosis (TAM-67-containing TAM-9 cells) showed that the sensitive cells expressed c-jun and jun D and the resistant cells TAM-67 AP-1 binding proteins after VES treatment. These studies suggested that c-jun may be involved in the apoptotic process initiated by VES treatment of human MCF-7 breast cancer cells.

The objective of this experiment was to test the hypothesis that early environmental influences could affect cardiovascular reactivity to acute stress in borderline hypertensive rats. This study utilized a cross-fostering paradigm in which borderline hypertensive rat (BHR) pups were reared by their natural spontaneously hypertensive rat (SHR) mothers, by an adoptive SHR dam, or by an adoptive Wistar-Kyoto female. Several maternal behavior measures were taken throughout weaning. Cardiovascular responses to acute stress were measured in adult BHR offspring. SHR dams spent significantly more time engaged in arched, as contrasted with passive, nursing behaviors throughout the preweaning period. Although strain of dam had no effect on resting blood pressure or heart rate, BHR reared by WKY dams had a greatly reduced blood pressure response to acute stress compared with BHR raised by either natural or adoptive SHR dams. These results suggest that the expression of cardiovascular characteristics in the BHR can be modified by early environmental influences and support the hypothesis that the expression of the hypertensive phenotype in the BHR is dependent upon information that is conveyed both genetically and environmentally.

MDA-MB-435 human breast cancer cells treated with 10 micrograms/ml of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for one, two, three, and four days exhibit 9%, 19%, 51%, and 73% apoptotic cells, respectively. Likewise, cells cultured for one, two, and three days with conditioned media (CM) obtained from MDA-MB-435 cells treated with VES exhibit 10%, 36%, and 74% apoptosis, respectively. A quantitative luciferase-based assay showed CM from VES-treated cells collected at 24 and 48 hours after treatment initiation to contain 75 and 32 pg of active transforming growth factor-beta (TGF-beta), respectively, per 10(6) cells. Although purified TGF-beta 1 is not an effective apoptotic agent for MDA-MD-435 cells, cotreatment of the cells for three days with suboptimal levels of VES (2.5 and 5 micrograms/ml) + 10 ng/ml of purified TGF-beta 1 enhanced apoptosis by 66% and 68%, respectively. Interference of the TGF-beta-signaling pathway by transient transfection of MDA-MB-435 cells with antisense oligomers to TGF-beta type II receptor (TGF-beta R-II) blocked VES-induced apoptosis. Likewise, addition of neutralizing antibodies to TGF-beta 1 or to all three mammalian isoforms of TGF-beta (TGF-beta 1, -beta 2, -beta 3) blocked VES- and CM-induced apoptosis. Furthermore, inhibitors of TGF-beta conversion from an inactive latent form to a biologically active form inhibited VES-induced apoptosis. In summary, the ability to reduce apoptosis by blocking TGF-beta or the TGF-beta receptor-signaling pathway with antisense oligomers or ligand-neutralizing antibodies or prevention of activation of TGF-beta indicates a role for TGF-beta signaling in VES-induced apoptosis.

RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.

In a large Denver HMO, a retrospective study of asthma management was reviewed. Seventy moderate to severe asthmatic patients' charts were reviewed through April 1994. All patients admitted to the study had to be followed for at least 1 year by a primary care physician before the allergy evaluation (AE) and for at least one year of followup (F/U) after the AE. All patients had at least two acute care (ER) visits and/or one hospitalization before the AE. All primary care, AE, and F/U were done by staff physicians in the Kaiser Permanente system. The findings included 1) Forty-five percent decrease (308 to 169) in the number of sick care office visits (P = 0.0001); 2) fifty-five percent decrease (266 to 118) in acute care visits (P = 0.0001); 3) sixty-seven percent decrease (34 to 11) in the number of hospitalizations after the AE (P = 0.001); 4) average hospital days before AE were four days and after AE, 2.5 days; 5) estimated cost saving of $145,500, or $2,100 per patient.

Objective: To determine whether a nutritional supplement of selenium will decrease the incidence of cancer., Design: A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial., Setting: Seven dermatology clinics in the eastern United States., Patients: A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years., Interventions: Oral administration of 200 microg of selenium per day or placebo., Main Outcome Measures: The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers., Results: After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred., Conclusions: Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made

The tissue deep to the iliotibial band (ITB) and its relationship to the lateral knee joint capsule was studied anatomically and the histopathology of this tissue in chronic iliotibial band friction syndrome (ITBFS) was examined. Findings show that the tissue under the ITB consists of a synovium that is a lateral extension and invagination of the actual knee joint capsule and is not a separate bursa as described in the literature. Additionally, in cases of chronic ITBFS seen in young elite athletes, synovial tissue taken from this lateral synovial recess reveals histological evidence of inflammation and hyperplasia that suggests its involvement in the pathological process.

Study Objective: To determine the rapidity and extent of core temperature decrease following release of a lower extremity pneumatic tourniquet., Design: Prospective study., Setting: Inpatient surgery in a university trauma center., Patients: 11 ASA status I and II adults undergoing unilateral lower extremity fracture fixation in which a tourniquet was used, with general anesthesia., Interventions: Temperature was measured in the esophagus before and after lower extremity tourniquet release., Measurements and Main Results: Tourniquet times ranged from 41 to 129 minutes (mean 98.5 +/- 9.1 minutes). Following tourniquet deflation core temperature decreased in all patients, with a maximal decline at 10 minutes, the termination of measurements, although trending downward. Esophageal temperature decreased an average of 0.46 degree C +/- 0.2 degree C at 5 minutes, and 0.67 degree C +/- 0.2 degree C at 10 minutes following tourniquet release, respectively. Temperature changes were significant (p = 0.0001) at both time intervals., Conclusion: Core temperature drops significantly immediately following release of the tourniquet at the esophageal temperature monitoring site. This decrease is the result of cooling of systemic blood reperfusing the hypothermic limb, and mixing of cool, "washed out" blood with the systemic circulation. As the consequences of hypothermia are well-known, we recommend core temperature monitoring in all patients having lower extremity tourniquet placed during general anesthesia, as well as vigilant monitoring for prolonged effects of anesthetics in the postoperative period.

From June 1994 to December 1995, 116 women (mean age 39 yrs, range 27-50 yrs) who met inclusion and exclusion criteria underwent endometrial ablation with a thermal balloon system. Forty-one (35%) were treated under general and 71 (61%) under neuroleptic anesthesia. Four (3%) treatments were performed under paracervical block only. A 16-cm long, 3-mm diameter catheter with a latex balloon at its tip housing a heating element was inserted into the uterus and filled with sterile 5% dextrose in water solution (mean 10.4 ml, range 2-55 ml). The catheter was connected to a control unit that maintained the temperature at 87 &plusmn; 5&deg; C, monitored the pressure, and terminated the treatment after 8 minutes. The starting uterine pressure was 80 to 140 mm Hg in the first 13 women and greater than 140 mm Hg in the rest. Nineteen women were treated for 12 minutes and all others for 8 minutes. Complications were endometritis (3), hematometra (2), and cystitis (1). At 6-month follow-up, after 8 minutes of treatment, persistent menorrhagia was reported by 38% and 12% of patients at less than and greater than 140 mm Hg pressure, respectively. At greater than 140 mm Hg pressure, menorrhagia was reported by 13% of women after 8 and 12 minutes of treatment. In 38 women, amenorrhea or spotting occurred in 29%, hypomenorrhea in 45%, eumenorrhea in 21%, and menorrhagia in 5%. Uterine balloon therapy is a safe and effective treatment for menorrhagia at uterine pressures of 150 to 180 mm Hg and of 8 minutes' duration.

The National Registry of Childhood Tumours contains over 51000 records of children born in Great Britain who developed cancer under the age of 15 years. Patterns of childhood cancer among families containing more than one child with cancer have been studied. A total of 225 "sib pair' families have been ascertained from interviews with parents of affected children, from hospital and general practitioner records and from manual and computer searches of names and addresses of patients. A number of special groups have been identified, including those with a known genetic aetiology such as retinoblastoma, twins and families with three or more affected children. A further 148 families not in any of the above groups contain two children with cancer: in 46 families the children had tumours of the same type, most commonly leukaemia. Some of the families are examples of the Li-Fraumeni syndrome; some are associated with other conditions, including Down's syndrome. There is clearly a genetic element in the aetiology of cancer in some families discussed here; shared exposure to environmental causes may account for others and some will be simply due to chance.

Background: Drug selection for optimal treatment of common medical conditions may be difficult and involve many diverse factors., Objective: The efficacy, safety, quality of life, and cost of treatment of seasonal allergic rhinitis with cetirizine, chlorpheniramine, or terfenadine were compared in a prospective, two-phase, randomized, single-blind clinical trial conducted in a managed care setting., Methods: In phase I, which lasted 2 weeks, patients were randomized to receive one of the study drugs. In phase II, which lasted 4 weeks, the initial treatment was continued unless patients were dissatisfied, in which case they could be randomly assigned to receive another study drug. In both phases pseudoephedrine could be taken as needed. Patients kept daily diaries of symptoms and costs, and study drugs were evaluated at the end of each phase for efficacy, safety, and effect on quality of life by means of a validated questionnaire. A multiattribute outcomes assessment model for formulary decision making was used to rank the antihistamines., Results: Physicians' and patients' assessments in phases I and II indicated that cetirizine and chlorpheniramine were significantly more effective than terfenadine (p < 0.05). Incidence of sedation in phase I and phase II was 40.5% and 16.7% for chlorpheniramine, 11.6% and 9.8% for cetirizine, and 6.7% and 5.1% for terfenadine, respectively. At the end of phase I, 28.9% of the patients treated with chlorpheniramine, 50% of the patients treated with terfenadine, and 69.4% of the patients treated with cetirizine were satisfied with their therapy and chose not to switch their medication. Quality of life scores improved most after treatment with cetirizine and least after treatment with terfenadine., Conclusion: The result of this trial indicate that antihistamine selection is best made with the use of a multiattribute evaluation that includes quality of life. In this study cetirizine was favored by patients and physicians most often, followed by chlorpheniramine and then terfenadine.

Objective: To propose clonazepam for use in the empiric treatment of shooting/shocking phantom limb pain., Setting: Outpatient pain clinic associated with a university hospital., Patients: Two patients with phantom limb pain after total hip disarticulation., Interventions: Treatment with clonazepam., Results and Conclusions: Clonazepam provided effective relief for > 6 months in two patients with shooting/shocking phantom limb pain. Although clonazepam therapy is not new, it appears to have been omitted from current pain texts and journals as a treatment option for phantom limb pain.

Preparticipation physical examinations are a prerequisite for competition at most levels of sports. This article discusses the unique opportunity that the health care team has to participate in the provision of sports assessment and screening services to a wide variety of individuals. In addition, this article reviews the purpose of the examination, organizational consideration, components of the examination, and special considerations that should be included.

A study describes the perception of unit nurse managers (head nurses/nurse executives) as to what constituted their role functions, activities and responsibilities. Four major components were used to clarify this description: administration, clinical practice, education and research.

The RRR-alpha-tocopheryl succinate form of vitamin E [vitamin E succinate (VES)] inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner, blocks the cells in the G2/M cell cycle phase, and induces the cells to undergo apoptosis. Apoptosis was documented by demonstrating changes that are characteristic of this type of cell death, including morphological analyses of chromatin condensation by 4',6-diamidine-2'-phenylindole dihydrochloride (DAPI) staining using scanning confocal and traditional fluorescent microscopy; flow cytometry analyses of propidium iodide-labeled DNA showing fragmented DNA as a pre-G1 peak; two-color flow cytometry analyses of intact cells labeled first by the TUNEL procedure (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end-labeled DNA stained with fluorescein isothiocyanate-labeled avidin) and then by propidium iodide demonstrating fragmented DNA; and electrophoresis of DNA showing a DNA ladder created by internucleosomal DNA fragmentation. The percentage of apoptotic cells was determined by DAPI staining and showed 11%, 27%, and 49% of cells to be apoptotic after treatment with 10 micrograms/ml VES for one, two, and three days, respectively. Analyses of mRNA levels of genes that have been implicated in the apoptotic process, namely, bcl-2, c-myc, and c-jun, revealed no change in bcl-2, decreases in c-myc mRNA levels after 36 hours of treatment, and increases in c-jun mRNA levels within four hours after treatment. Western immunoblotting analyses of protein levels for the transcription factors c-Myc and c-Jun showed normal levels of c-Myc at early time points and decreased levels at 24 and 48 hours after treatment. c-Jun increased as early as 6 hours after treatment and returned to lower (yet still elevated over control) levels by 48 hours. To determine possible functional consequences of increased c-Jun expression, gel electrophoretic mobility assays were conducted that showed increased AP-1 binding at 24 and 48 hours after treatment. These data show that VES induces apoptosis in reticuloendotheliosis virus-transformed lymphoid cells and suggest that decreases of c-Myc protein and increases of c-Jun protein and DNA binding capacity may be playing a role in VES-mediated events leading to apoptosis in this cell type.

RRR-alpha-tocopheryl succinate (VES) was studied for effects on murine EL-4 cell proliferation and production of interleukin-2 (IL-2) and transforming growth factor-beta (TGF-beta). VES was biphasic in its actions: 0.1 microgram/ml enhanced EL-4 cell proliferation, whereas 10-20 microgram/ml inhibited cellular proliferation. Cell-conditioned media (CM) from EL-4 cells treated with 0.2 ng/ml phorbol myristate acetate (PMA) + 0.1 microgram/ml VES contained increased amounts of IL-2, as determined by the murine cytotoxic T cell IL-2-dependent CTLL-2 bioassay. VES at 0.1 microgram/ml or 0.1 microgram/ml VES + 0.2 ng/ml PMA induced the expression of IL-2 mRNA by EL-4 cells three to nine hours after treatment. CM from EL-4 cells treated with VES at 10-20 microgram/ml exhibited potent antiproliferative activity when tested in the TGF-beta-responsive mink lung cell (Mv1Lu) bioassay and showed reduced inhibitory effects when tested on TGF-beta receptor-negative mink lung (DRA-27) cells. CM from control-treated EL-4 cells exhibited no antiproliferative activity. The VES-induced antiproliferative activity was characterized as TGF-beta by neutralization analyses and immunoprecipitation of metabolically labeled proteins with TGF-beta-specific reagents. VES treatment of EL-4 cells had no effect on TGF-beta 1 mRNA expression while downregulating TGF-beta 3 mRNA expression. In summary, these studies showed that 0.1 microgram/ml VES enhanced cellular proliferation, in part, via increased IL-2 production, whereas 10-20 micrograms/ml VES inhibited cellular proliferation, in part, via the secretion of biologically active TGF-beta.

The proliferation of MDA-MB-435 human breast cancer cells was inhibited by RRR-alpha-tocopheryl succinate (vitamin E succinate, VES). Conditioned media (CM) from VES growth-inhibited cells contained potent antiproliferative activity, part of which is contributed by transforming growth factor-beta (TGF-beta) isoforms. Antibody neutralization analysis, employing TGF-beta isoform-specific antibody reagents, showed that TGF-beta 1, -beta 2, and -beta 3 were present in the CM from VES-treated cells. Culturing MDA-MB-435 cells with VES did not alter the levels of constitutively expressed 2.4-kb TGF-beta 1, 3.0- and 4.0-kb TGF-beta 2, or 1.2- and 3.5-kb TGF-beta 3 mRNA transcripts. Inhibition of DNA synthesis by MDA-MB-435 cells was increased by combinations of suboptimal levels of VES and purified TGF-beta 1. VES-treated MDA-MB-435 cells exhibited enhanced binding of radiolabeled TGF-beta 1, and Western immunoblotting analyses showed that VES treatment enhanced TGF-beta type II receptor protein expression. TGF-beta type I receptor protein levels were not modified by VES treatments. Although the mRNA transcript for the 5.5-kb TGF-beta type II receptor was upregulated after four hours of treatment with VES, this treatment did not modify the 6.5-kb TGF-beta type I or the 6.5-kb TGF-beta type II receptor mRNAs. Results demonstrate that biologically active TGF-beta 1, -beta 2, -beta 3 and levels of TGF-beta type II receptor expressed by human breast cancer cells are enhanced by VES treatment.

This article discusses the orthodontist's involvement in treating patients with complex temporomandibular joint (TMJ) disorders. It includes a review of the literature and information regarding classification, epidemiology, incidence, and diagnosis of TMJ internal derangements. Controversies in management discussed include the importance of disc position, the consequences of not repositioning the disc, and the predictability of progression of disease. Considerations regarding home care, medical care, and surgical care are also presented.

Some dental professionals may have concerns about treating patients who have seizure disorders. The authors contend that increased knowledge about seizures and how to manage them may make dental professionals more comfortable. This article reviews the various seizure types, discusses commonly used anticonvulsants and their side effects and outlines some special concerns dentists may have in providing care to these patients.

Health care professionals often inappropriately separate dental health from other health functions. Baby bottle tooth decay (BBTD) should be a concern for all professionals who work with expectant or new mothers and very young children. Research indicates that even though many mothers are aware of the etiology of the condition, they continue to allow prolonged nursing with milk or liquids other than water. Nurses can help promote good oral health for children by educating and training expectant and new mothers, children, and others who work with mothers and children in preventing BBTD.

In the present study we characterize the stress response induced by copper in the fathead minnow, Pimephales promelas. The fathead minnow epithelial cell line ATCC CCL 42 was used to examine the induced synthesis and subcellular localization of the two major stress proteins, stress 70 and cpn60. Western blot analysis demonstrated increased stress70 in cells exposed to 400 and 500 microM Cu. Two-dimensional analysis revealed three isoforms of stress70, one of 70 kDa and two of 72 kDa, at the highest Cu concentration. Chaperonin60 abundance did not change over the same range of Cu concentrations. Indirect immunofluorescence microscopy revealed that stress70 localized in the cytoplasm, particularly in the paranuclear region. Chaperonin60 was localized in mitochondria. Further, when we examined the stress response elicited by Cu in fathead minnow larvae in vivo, we found that Cu induced the stress response at nominal Cu concentrations that were more than an order of magnitude lower that in the cell culture. This disparity between the concentration of Cu, which induced the stress response in cells in culture and in vivo, may be the result of differences in Cu complexation that alter its availability, uptake and toxicity.

A study of 301 college undergraduates is employed to test a causal model which proposes that dissociation and depression act as mediator variables that develop from child abuse and lead to various negative outcomes. As predicted, child maltreatment was found to be related to negative life experiences, with depression and dissociation differentially mediating the various outcomes.

Objective: To develop and prospectively evaluate criteria for selecting head-injured patients requiring cranial CT., Methods: A two-phased prospective observational study design was implemented at a university ED. Physicians completed a form with 51 variables for 540 patients in Phase I. Ten high-yield variables were identified and prospectively tested on 273 patients in Phase II. Prediction rule performance for identification of patients with abnormal CT scans was determined., Results: The combined criteria had a sensitivity of 97% for CT-scan abnormalities in Phase I; sensitivity was 96% in Phase II. Negative predictive values were 97% and 94%, respectively. Prevalence of disease in Phase I was 17%; prevalence in Phase II was 16%. Had the Phase I criteria been implemented during Phase II, 43 of 273 patients (16%) would not have been scanned, including two patients with positive results who did not require operative intervention., Conclusions: Fifty-one clinical variables from head-injured patients were narrowed to ten of statistical significance and consistent interpretation for prospective evaluation. Patients with none of these criteria were found to be at low risk of having sustained significant head injury.

This paper describes a self-report measure, the Child Abuse and Trauma Scale, which yields a quantitative index of the frequency and extent of various types of negative experiences in childhood and adolescence. Data on this measure are presented for two large samples of college students and for a small clinical sample of subjects with a diagnosis of Multiple Personality Disorder. The strong internal consistency and test-retest reliability of the scale in the college population is documented, and its validity is attested to by demonstrating that it correlates significantly with outcomes such as dissociation, depression, difficulties in interpersonal relationships, and victimization, all of which have previously been associated with childhood trauma or abuse. The extremely high scores of the Multiple Personality subjects confer additional validity to the measure. The authors suggest that the construct of psychological maltreatment underlies the destructive elements of numerous forms of abuse and neglect, and that the scale they have developed may provide a useful index of this construct.

Purpose: The purpose was to test the outcome of a custom computer assisted design/computer assisted manufactured (CAD/CAM) total temporomandibular joint (TMJ) reconstruction system., Patients and Methods: There were 215 patients (13 males and 202 females); the average age at reconstruction was 40.9 +/- 10.3 years (range, 15 to 77 years). There were 363 joints placed, 296 bilateral and 67 unilateral. The patients had TMJ problems for an average of 10.3 +/- 7.0 years (range, 1 to 44 years), and had undergone a mean of 5.4 +/- 4.8 (range, 0 to 28) prior unsuccessful surgeries. Preoperative and postoperative data were collected for up to 48 months using a standardized data collection format. Subjective data related to pain, function of the lower jaw, and diet, were obtained using a visual analogue scale. Objective measures of mandibular range of motion were made directly on the patient preoperatively and postoperatively., Results: Preliminary analysis of these data reveals a statistically significant decrease in pain, an increase in function, and improvement in diet (P < .0001) from the preoperative measurements to 1 and 2 years postoperatively. There was also improvement in mandibular vertical range of motion. The number of previous surgeries was a strong predictor of postoperative pain, function, and diet scores, as well as of maximal interincisal opening. A life table analysis of failures indicates good durability of the prosthesis over time., Conclusion: These preliminary data indicate that this custom CAD/CAM total TMJ reconstruction system seems to be useful in the treatment of the multiply operated, and/or anatomically mutilated TMJ.

The RRR-alpha-tocopheryl succinate form of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner in vitro. Analyses of conditioned medium (CM) from VES growth-inhibited cells revealed a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of TGF-beta-responsive Mv1Lu mink lung and murine CTLL-2 cell lines, 2) a combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, 3) neutralization of the antiproliferative activity by antibodies specific for TGF-beta, and 4) immunoprecipitation of metabolically labeled TGF-beta in CM from VES-treated C4-1 cells by use of TGF-beta-specific antibodies. Northern blot analyses of total cellular RNA revealed that VES does not alter the levels of constitutively expressed TGF-beta isoform-specific mRNAs; namely, VES does not alter the levels of the 3.9- and 4.1-kb TGF-beta 2 mRNAs, the 3.0-kb TGF-beta 3 mRNA, or the 2.5-, 2.7-, and 1.7-kb TGF-beta 4 mRNAs. The data show that VES inhibits C4-1 cell proliferation and induces the cells to produce and secrete active forms of TGF-beta, suggesting that one mechanism whereby VES inhibits C4-1 cell proliferation may be via the TGF-beta pathway for cellular growth control.

HL-60 cells, growing as single cells in suspension, exhibit marked cell-cell adhesion when treated for 24 hours with 10 micrograms/ml RRR-alpha-tocopheryl succinate, also called vitamin E succinate (VES). VES-induced cell-cell adhesion is dependent on divalent cations and a functional cytoskeleton and is protein mediated. Cell adhesion molecules CD11a/CD18, CD11b/CD18, CD29, and CD54 do not appear to be mediating VES-induced cell adhesion. HL-60 cells treated with VES adhere to fibronectin-coated plastic and secrete elevated levels of fibronectin. A 72-kDa fibronectin-binding membrane molecule was detected on VES-treated HL-60 cells, and antibodies to fibronectin were shown to inhibit VES-induced cell aggregation. VES induction of HL-60 cell-cell adhesion is proposed to result from increased amounts of extracellular fibronectin binding to VES-induced cell surface fibronectin-binding molecules.

There is epidemiological, laboratory and some clinical evidence that certain dietary factors play a role in either promoting or inhibiting cancer development. An understanding of the mechanisms whereby specific nutrients are having effects in the promotion or prevention of cancer is beginning to take shape. Research into nutrient effects on the expression of specific genes, especially cytokine and cytokine receptor expression, will help increase our basic knowledge of cancer biology. Since cytokines can either enhance or suppress both immune defense and cancer growth, increased understanding of nutrient effects on the cytokine network will be beneficial. The regulation of specific gene expression by specific nutrients, indeed, identifies a major frontier for present and future nutritional biologists.

The RRR-alpha-tocopheryl succinate derivative of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of three metastatic human prostatic cancer cell lines, LNCaP, PC-3, and DU-145. LNCaP is a lymph node-derived androgen-sensitive prostate cell line; these cells are defective for response to transforming growth factor-beta (TGF-beta) but are normal for cell cycle-related tumor suppressor genes: p53 and retinoblastoma (Rb). PC-3 is a bone marrow-derived androgen-insensitive prostate cell line; these cells are defective for both p53 alleles but normal for both Rb alleles. DU-145 is a brain-derived androgen-insensitive prostate cell line; these cells are defective for both p53 and both Rb alleles. VES at 5, 10, and 20 micrograms/ml inhibited DNA synthesis in the three cell lines in a dose-dependent manner. Purified TGF-beta 1 at 1 ng/ml inhibited DNA synthesis of PC-3 cells within 24-72 hours and DU-145 cells at 72 hours but did not inhibit DNA synthesis of LNCaP cells. Previous studies in our laboratory showed that VES growth-inhibited tumor cells secrete biologically active antiproliferative factor TGF-beta s, suggesting that VES's mechanism of growth inhibition may involve the TGF-beta system of growth control.(ABSTRACT TRUNCATED AT 250 WORDS)

This experiment investigated whether forced single-nostril breathing differentially affects cognitive abilities presumed to be mediated by the left and right cerebral hemispheres. Phase I was an attempted replication of a reported sex difference in the effects of unilateral breathing on verbal versus spatial performance and Phase II was a study of breathing effects on different verbal and spatial tests. No differences associated with breathing condition were found in the replication study. In Phase II, men breathing through the right nostril scored significantly lower than men in the control condition on a letter-matching test although they did not differ significantly from men in the left-nostril condition on that test. There were no significant breathing-related differences on two spatial tests, and no differences associated with breathing condition for the women. Assessment of nostril dominance before and after cognitive testing showed that the forced-breathing exercise did not significantly alter subjects' nostril dominance. A significant left-nostril bias was found in this sample.

A major component of the cellular stress response entails the induced synthesis of a suite of stress proteins under environmentally adverse conditions that functions to protect organisms from environmentally induced damage. Here, we examined induction of the stress response in the embryos of the sea urchin Strongylocentrus purpuratus under a combination of environmentally realistic conditions. First, we examined the response elicited over a range of free cupric ion activities, (Cu2+), using a metal buffer system to control trace metal speciation. We observed no pronounced differences in translational patterns in embryos exposed to free cupric ion activities, (Cu2+), of 10(-13)-10(-9) M by metabolic labeling, 1-dimensional electrophoresis and autoradiography. Further separation by 2-dimensional electrophoresis, however, revealed electrophoretically discernable variants of several groups of proteins at the higher Cu concentrations and the synthesis of a 60 kDa protein at (Cu2+) of 10(-9) M. In addition, there were differences in the stress response induced by heat-shock treatment in embryos cultured in seawater with different Cu concentrations; radiolabel was incorporated into a greater number of cellular proteins in embryos at lower (Cu2+) and the induced synthesis of stress proteins was greater. These data suggest that elevations in (Cu2+) impair the ability of the embryos to mount the stress response upon exposure to elevated temperatures and that Cu may alter critical developmental pathways by inhibiting the synthesis of regulatory proteins. Such effects on gene expression can result in manifestations that have been widely attributed to Cu toxicity, including developmental abnormalities and increased sensitivity to environmental extremes. We suggest that the particular sensitivity of embryonic systems upon exposure to multiple stressors may be a consequence of these mechanisms.

This study examines the expression and accumulation of two major stress proteins, stress70 and chaperonin60 (cpn60), in the gill and mantle of blue mussels, Mytilus edulis, which were exposed to a range of Cu concentrations for 7 days. Scope-for-growth (SFG), mortality, and Cu accumulation in gill and mantle tissue were also measured to monitor the physiological effects of Cu exposure in the organisms. In general Cu accumulated to a greater extent in gill relative to mantle tissue. A reduction of SFG index and increased mortality was also observed at the two highest Cu concentrations. We found no significant differences between the two tissues in the expression of cpn60 and stress70 for mussels exposed to Cu ranging from 0 to 10 micrograms/liter Cu (cpn60) and 0 to 32 micrograms/liter Cu (stress70) in sea-water. However, differences in the stress response were observed between the gill and the mantle tissue of mussels exposed to higher Cu concentrations. Chaperonin concentrations were greater than an order of magnitude higher in the gill than in the mantle for these mussels. Further, although the accumulation of stress70 was similar between the two tissues, two additional proteins reacted with antibody to stress70 in gill, but not mantle tissue, of mussels exposed to 100 micrograms/litter Cu. This study suggests that the physiological processes involved in contaminant uptake, distribution, and detoxification may affect the tissue-level expression of the stress response in multicellular organisms. Further, the intensity of the stress response and relative concentrations of chaperonin and stress70 among tissues may help identify tissues which are the most vulnerable to damage caused by a particular environmental stressor.

This study evaluated the effect of preoperative sleep on the success of conscious sedation. Thirty healthy children between the ages of 18 and 61 months of age were utilized in this study. The children all received chloral hydrate (50-60 mg/kg) and hydroxyzine (15-25 mg) and nitrous oxide (30-50%). Parents were asked to complete a questionnaire which asked several questions about their child's activity the previous day, their diet, and questions that related to their bedtime. The operator ranked the sedations on a scale from 1 to 4 with 1 being good and 4 being poor. The results were then statistically evaluated using the non-parametric Mann-Whitney and Kruskal-Walls tests. The children that received a normal amount of sleep or greater amount of sleep preoperatively had a borderline (P = .06) higher degree of successful sedation. There was no correlation between the child's bedtime (early, normal, late) and the success of sedation. The parent's perception of their child's tiredness could not be correlated with the success of the sedation. The children greater than 36 months of age had a significantly (P = .02) higher degree of successful sedations. The results suggest that a well rested child may experience a more pleasant dental sedation while under chloral hydrate and hydroxyzine conscious sedation and that the child's age at the time of the sedation may affect the outcome of the sedation.

This study compares vascular responses of unstressed borderline hypertensive rats (BHR) to age-matched Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Rings of thoracic aorta were mounted for isometric force determinations in tissue baths. Cumulative additions of phenylephrine (PE) or serotonin (5-HT) produced contractile responses in BHR aorta that were less than WKY but greater than SHR. Removing the endothelium increased force development to both agonists, with BHR showing the greatest increase. Based on EC50 determinations, no differences in PE sensitivity existed between groups, although in response to 5-HT, rings from SHR were significantly more sensitive than WKY. While the sensitivity of all rings increased with denuding, BHR showed a greater relative increase in sensitivity than WKY or SHR (intact EC50 divided by denuded EC50) to both PE and 5-HT. This suggests that there may be greater endothelium-derived relaxation in BHR than in WKY or SHR. In rings precontracted with 1 microM PE, the cumulative addition of acetylcholine resulted in greater relaxation in BHR than in SHR and WKY preparations. Thus, rings from unstressed BHR, which have only slightly higher blood pressures than WKY rats, demonstrate greater endothelium-mediated relaxation than WKY or SHR. Increased endothelium-derived relaxation may represent a possible mechanism for masking hypertension in BHR that is compromised as a result of exposure to a chronic stress paradigm.

We report in the present paper that proteins which react with a polyclonal antibody (pAb) raised against the heat-shock protein chaperonin60 (cpn60) were revealed by indirect immunofluorescence in the nucleus of a fish (fathead minnow, Pimephales promelas) cell line after heat-shock. This immunoreactive cpn60 associated with the nucleolus and with discrete foci. An increased abundance of two nuclear proteins of approx. 57 and 42 kDa, present in approximately equal amounts, was detected by Western blotting using an anti-cpn60 pAb as a probe during the same time period that cpn60 was revealed in the nucleus. These proteins also reacted with a monoclonal antibody (mAb) against human cpn60 but did not react with an mAb against the cytoplasmic chaperonin, TCP1. The kinetics of translocation and pattern of nuclear localization of this immunoreactive cpn60 differed from that of stress70, another major family of heatshock proteins. We suggest that these nuclear immunoreactive cpn60 proteins are members of the cpn60 family and that they play a chaperone role in folding and assembly of proteins in the nucleus which is distinct from that of stress70.

Stress proteins have been shown to provide information on the biological impact of toxic chemicals to organisms and to predict adverse consequences of that exposure. In this study we have examined the accumulation to two major stress proteins, hsp60 and hsp70, in banked samples to determine if they accumulate at high levels in organisms exposed to contaminants in their environment. We found that relative to laboratory controls, stress proteins concentrations were elevated in mussels and fish tissue collected as part of the NOAA National Status and Trends Program. Sediment and water chemistry from the stations where these organisms were collected and data on contaminant body burdens of these same organisms indicated that they had been exposed to contaminants for long durations in their environment. This study suggests that stress protein accumulation may provide a method for quantifying adverse biological impacts of exposure to chemicals in the environment when examined in wild populations from contaminated sites. This approach may also prove valuable in retrospective studies when used in banked specimens which have been collected as part of a large scale surveillance monitoring programs.

Black athletes currently dominate long-distance running events in South Africa. In an attempt to explain an apparently superior running ability of black South African athletes at distances > 3 km, we compared physiological measurements in the fastest 9 white and 11 black South African middle-to long-distance runners. Whereas both groups ran at a similar percentage of maximal O2 uptake (%VO2max) over 1.65-5 km, the %VO2max sustained by black athletes was greater than that of white athletes at distances > 5 km (P < 0.001). Although both groups had similar training volumes, black athletes reported that they completed more exercise at > 80% VO2max (36 +/- 18 vs. 14 +/- 7%: P < 0.005). When corrections were made for the black athletes' smaller body mass, their superior ability to sustain a high %VO2max could not be explained by any differences in VO2max, maximal ventilation, or submaximal running economy. Superior distance running performance of the black athletes was not due to a greater (+/- 50%) percentage of type I fibers but was associated with lower blood lactate concentrations during exercise. Time to fatigue during repetitive isometric muscle contractions was also longer in black runners (169 +/- 65 vs. 97 +/- 69 s; P < 0.05), but whether this observation explains the superior endurance or was due to the lower peak muscle strength (46.3 +/- 10.3 vs. 67.5 +/- 18.0 Nm/l lean thigh volume; P < 0.01) remains to be established.

Several investigators have used meta-analysis to compare the results of studies of gender differences on various spatial tests and have concluded that the magnitude of the gender difference in spatial ability is decreasing over time. The present study used meta-analytic techniques to compare the effect size (d) of the gender difference in 14 studies published from 1975 to 1992 which administered the Mental Rotations test to adolescents and young adults. Males scored significantly higher than females in all the studies. Analyses of the d's computed for the studies revealed that the magnitude of the gender difference on the Mental Rotations test has remained stable over time. Neither the Pearson correlation relating the d's to the publication dates of the studies nor the Z test of the linear contrast relating the publication dates of the studies to the effect sizes showed a linear change in the size of the gender difference over time. The finding of a stable gender difference on the Mental Rotations test argues against the general conclusion that the gender difference in spatial ability is decreasing.