Ethnic, racial and cultural identity and perceived benefits and barriers related to genetic testing for breast cancer among at-risk women of African descent in New York City.

BACKGROUND: Due to disparities in the use of genetic services, there has been growing interest in examining beliefs and attitudes related to genetic testing for breast and/or ovarian cancer risk among women of African descent. However, to date, few studies have addressed critical cultural variations among this minority group and their influence on such beliefs and attitudes. METHODS: We assessed ethnic, racial and cultural identity and examined their relationships with perceived benefits and barriers related to genetic testing for cancer risk in a sample of 160 women of African descent (49% self-identified African American, 39% Black-West Indian/Caribbean, 12% Black-Other) who met genetic risk criteria and were participating in a larger longitudinal study including the opportunity for free genetic counseling and testing in New York City. All participants completed the following previously validated measures: (a) the multi-group ethnic identity measure (including ethnic search and affirmation subscales) and other-group orientation for ethnic identity, (b) centrality to assess racial identity, and (c) Africentrism to measure cultural identity. Perceived benefits and barriers related to genetic testing included: (1) pros/advantages (including family-related pros), (2) cons/disadvantages (including family-related cons, stigma and confidentiality concerns), and (3) concerns about abuses of genetic testing. RESULTS: In multivariate analyses, several ethnic identity elements showed significant, largely positive relationships to perceived benefits about genetic testing for breast and/or ovarian cancer risk, the exception being ethnic search, which was positively associated with cons/disadvantages, in general, and family-related cons/disadvantages. Racial identity (centrality) showed a significant association with confidentiality concerns. Cultural identity (Africentrism) was not related to perceived benefits and/or barriers. CONCLUSIONS: Ethnic and racial identity may influence perceived benefits and barriers related to genetic testing for breast and/or ovarian cancer risk among at-risk women of African descent. Genetic counseling services may want to take into account these factors in the creation of culturally-appropriate services which best meet the needs of this heterogenous population.

Exercise-induced HSP27, HSP70 and MAPK responses in human skeletal muscle.

AIM: The present work examined protein and messenger RNA (mRNA) expression of intramuscular heat shock protein 27 (HSP27), heat shock cognate (HSC70) and HSP70 in human biceps brachii (BB) and vastus lateralis (VL) subsequent to two different exercises. METHODS: Untrained subjects performed 50 high-force eccentric contractions with their non-dominant BB and ran downhill (-10 degrees) for 30 min. The 48-h PX stress response was evaluated with immunoblotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Muscle damage was indicated indirectly at 48 h post-exercise (PX) [loss of mobility, muscle soreness and serum creatine kinase (CK) activity]. RESULTS: On the protein level, HSP27 and HSP70 increased significantly PX in the BB (384 and 227%, respectively; P < 0.01), but there were no significant HSP changes in the VL or in HSC70 in either muscle. The RT-PCR data complemented these findings: BB HSP27 and HSP70C mRNA levels increased (135 and 128%, respectively; P < 0.05); in the VL only HSP70B increased (206%; P < 0.05). Phosphorylation of e-jun NH2-terminal kinase (JNK) and extracellular regulated kinase (ERK) increased significantly in the BB (226 and 200%, respectively; P < 0.05) but not in the VL, indicating activation of these pathways only after the resistance exercise. CONCLUSION: These data indicate that the PX HSP and mitogen-activated protein kinase responses are exercise-specific and local, not systemic. Further, only the resistance exercise induced HSP expression (protein and mRNA) and JNK/ERK activation at 48 h PX, suggesting that these molecules may be important to long-term skeletal muscle adaptations such as hypertrophy.

The repeated bout effect and heat shock proteins: intramuscular HSP27 and HSP70 expression following two bouts of eccentric exercise in humans.

Exercise-induced damage significantly and predictably alters indirect indicators of muscle damage after one bout of damaging exercise but this response is dampened following a second bout of the same exercise performed 1-6 weeks later. Previously we have described a marked increase in the levels of heat shock proteins (HSPs) HSP27 and HSP70 in human biceps muscle following one bout of high-force eccentric exercise. The purpose of the present study was to examine the intramuscular HSP27 and HSP70 response following two identical bouts of exercise [bout 1 (B1) and bout 2 (B2), separated by 4 weeks] relative to indirect indices of muscle damage. Ten human subjects performed 50 high-force eccentric contractions with their non-dominant forearm flexors; muscle damage of the biceps brachii was evaluated 48 h post-exercise with indirect indices [serum creatine kinase (CK) activity, soreness, isometric maximal voluntary contraction (MVC) force and relaxed arm angle] and immunoblotting of high ionic strength muscle biopsy extracts for both HSPs. Not unexpectedly, the indirect indicators of damage changed dramatically and significantly (P < 0.01) after B1 but had a much smaller response after B2. The magnitude of the HSP response was the same after both bouts of exercise, though the control and exercised samples of B2 demonstrated a lower basal HSP expression. Thus, though both indirect and cellular indicators of exercise-induced muscle damage demonstrate an adaptation consequent to the first bout of exercise, these adaptations are quite different. It is possible that the lower basal HSP expression of the cellular response mediates the attenuation of damage associated with B2 as indicated by indirect indices.

A single bout of eccentric exercise increases HSP27 and HSC/HSP70 in human skeletal muscle.

Changes in heat shock proteins (HSPs), HSP27 and HSC/HSP70 were characterized in human biceps brachii muscle following damaging high-force eccentric exercise. Male and female volunteers performed a maximal eccentric resistance exercise with the elbow flexor muscles of the non-dominant arm known to be sufficient to cause substantial muscle damage. Protein extracts of biopsy tissue samples taken 48 h post-exercise were immunoblotted for HSC/HSP70 and HSP27. Densitometric analysis demonstrated that these proteins increased significantly (P < 0.01) in the damaged biceps brachii relative to the control arm. The HSC/HSP70 increased 1064% in the exercised sample while HSP27 increased by 234%. Although the literature reports a muscular heat shock response following aerobic, oxidative exercise, this is the first documentation of increases in protein expression of both HSC/HSP70 and HSP27 in human skeletal muscle in response to a single bout of resistance exercise.

Antioxidants: what role do they play in physical activity and health?

Exercise appears to increase reactive oxygen species, which can result in damage to cells. Exercise results in increased amounts of malondialdehyde in blood and pentane in breath; both serve as indirect indicators of lipid peroxidation. However, not all studies report increases; these equivocal results may be due to the large intersubject variability in response or the nonspecificity of the assays. Some studies have reported that supplementation with vitamins C and E, other antioxidants, or antioxidant mixtures can reduce symptoms or indicators of oxidative stress as a result of exercise. However, these supplements appear to have no beneficial effect on performance. Exercise training seems to reduce the oxidative stress of exercise, such that trained athletes show less evidence of lipid peroxidation for a given bout of exercise and an enhanced defense system in relation to untrained subjects. Whether the body's natural antioxidant defense system is sufficient to counteract the increase in reactive oxygen species with exercise or whether additional exogenous supplements are needed is not known, although trained athletes who received antioxidant supplements show evidence of reduced oxidative stress. Until research fully substantiates that the long-term use of antioxidants is safe and effective, the prudent recommendation for physically active individuals is to ingest a diet rich in antioxidants.

An anisocoria produces a small relative afferent pupillary defect in the eye with the smaller pupil.

OBJECTIVES: To determine whether an anisocoria can produce a relative afferent pupillary defect of clinical importance. MATERIAL AND METHODS: Anisocoria and relative afferent pupillary defect were measured with infrared videography in three clinical experiments: 1) every few minutes in eight normal subjects who remained in darkness as one pupil was dilating from mydriatic drops; 2) every 2 hours, for 8 hours in six normal subjects who remained in room light after one pupil was dilated with mydriatic drops; and 3) before and after dilation of one pupil in 24 patients with known afferent defects from optic nerve disease and who remained in room light. RESULTS: In the presence of an anisocoria, the relative afferent pupillary defect was almost always in the eye with the smaller pupil. The results of the three experiments were: 1) In darkness, the induced pupillary defect was found to be related to the ratio of the areas of the two pupils (R = 0.942), and 0.14 log unit of pupillary defect was produced in the eye with the smaller pupil for every millimeter of anisocoria. 2) In room light, the induced pupillary defect was in the eye with the smaller pupil but was less than in Experiment 1 and persisted throughout the 8 hours. This was presumably because the eye with the larger pupil had become more light adapted in the clinic light than the eye with the smaller pupil. 3) In room light, inducing an anisocoria in patients with preexisting afferent pupillary defect tended to shift the pupillary defect toward the eye with the smaller pupil (R = 0.68). CONCLUSIONS: Clinically, approximately 0.1 log unit of relative afferent pupillary defect is produced in the eye with the smaller pupil for every millimeter of anisocoria. Therefore, the anisocoria must be larger than 2 mm in diameter difference to induce a clinically significant relative afferent pupillary defect.

Psychosocial mediators of racial differences in nighttime blood pressure dipping among normotensive adults.

Shallow declines in nocturnal compared with diurnal blood pressure (BP dipping) have been associated with cardiovascular disease. In U.S. samples, Blacks demonstrate less BP dipping compared with Whites. In a sample of 60 Black and 60 White normotensive adults we examined stress, social integration (including parental status), social support, and hostility as potential mediators of the association between race and BP dipping. The effect of race on diastolic BP dipping was partially mediated by parental status. The effect of race on heart rate dipping was partially mediated by stressful life events. No psychosocial factors mediated the relation between race and systolic BP dipping. Although psychosocial factors appear to account for some of the observed racial differences in nocturnal blood pressure decline, our data suggest that these differences cannot be attributed entirely to covarying psychosocial effects.

Phase I safety and antigenicity of TA-GW: a recombinant HPV6 L2E7 vaccine for the treatment of genital warts.

A phase I double-blind, randomized, placebo-controlled study was carried out in healthy subjects to assess the safety and immunogenicity of TA-GW, a recombinant HPV6 L2E7 fusion protein vaccine for the treatment of genital warts. Forty-two healthy male volunteers were randomised to receive three intramuscular injections of either 0, 3, 30 or 300 microg of recombinant L2E7 adsorbed onto Alhydrogel. Two vaccination schedules were compared: weeks 0, 1 and 4 (accelerated schedule) and weeks 0, 4 and 8 (classical schedule). Subjects were monitored for adverse events throughout. Immunogenicity was assessed by measuring L2E7 specific in vitro T cell proliferative responses, production of IFNgamma and IL-5 and serum antibodies. Dose-dependent and long-lived T and B cell immune responses were elicited by TA-GW with both vaccination schedules. In conclusion, TA-GW is both safe, well-tolerated and immunogenic. The results allow the selection of the 300-microg vaccine formulation and accelerated vaccination schedule for phase II trials in patients with genital warts.

Phase IIa safety and immunogenicity of a therapeutic vaccine, TA-GW, in persons with genital warts.

A fusion protein vaccine consisting of human papillomavirus 6 L2E7 with Alhydrogel was developed for the treatment of genital warts. Twenty-seven subjects with genital warts received 3 immunizations over 4 weeks in an open-label study. The vaccine was well-tolerated, and all subjects made serum IgG antibodies, predominantly IgG1, against L2E7. Nineteen of 25 tested persons made antigen-specific T cell proliferative responses to L2E7, and peripheral blood mononuclear cells when cultured with L2E7 in vitro produced both interferon-gamma and interleukin (IL)-5, although IL-5 predominated after the final vaccination. Five subjects completely cleared warts within 8 weeks. Subjects whose warts were not cleared by 8 weeks were offered conventional therapy. Recurrence of warts was not seen in any of the 13 persons whose warts cleared by vaccine alone or with conventional therapy. While these preliminary results of the use of this therapeutic immunogen are encouraging, proof of efficacy will require randomized double-blind trials.

Enhanced immunogenicity of a recombinant genital warts vaccine adjuvanted with monophosphoryl lipid A.

The regression of genital warts is believed to be a T-cell-mediated immune effect. We have sought to enhance the immunogenicity of a therapeutic vaccine for the treatment of genital warts with the use of the adjuvant monophosphoryl lipid A (MPL-immunostimulant), a detoxified form of the lipopolysaccharide (LPS) of Salmonella minnesota R595. The comparative immunogenicity and reactogenicity of a recombinant human papillomavirus type 6 (HPV6) L2E7 fusion protein in either aqueous, oil-in-water emulsions or Alhydrogel formulations containing MPL was evaluated. We conclude that the simple addition of MPL to the L2E7 fusion protein already adsorbed onto Alhydrogel preferentially enhances antigen specific in vitro T-cell proliferative responses, IFN gamma production and in vivo delayed type hypersensitivity responses without increasing its reactogenicity.

Segmental denervation and reinnervation of the iris sphincter as shown by infrared videographic transillumination.

OBJECTIVE: This study aimed to analyze the denervation and reinnervation history of individual segments of the iris sphincter in patients with Adie's syndrome. DESIGN: The irises of these patients were retroilluminated by shining an infrared-rich light through the lower eyelid and sclera and viewing the transilluminated iris from the front with an infrared-sensitive video camera. The irises of the same group of patients also were videotaped through a slit-lamp camera using routine frontal illumination. Both of these techniques also were used to examine a series of normal subjects. PARTICIPANTS: A total of 61 patients with Adie's syndrome or Adie's-like denervation of the iris sphincter (from surgery, trauma, or radiation) and 10 normal subjects were studied. MAIN OUTCOME MEASURES: Slit-lamp examination results of the segmental movement of the iris were compared to the infrared transillumination pattern of the iris sphincter before and during the light reflex, before and during the near-vision reaction, before and during eye movement, and before and after the application of dilute pilocarpine and 1% pilocarpine. RESULTS: Whenever an iris sphincter segment contracted, it also became denser by using these techniques. Reinnervated iris segments failed to contract to light but did contract and became denser with a near effort or with eye movement. Segments supersensitive to pilocarpine became denser than adjacent segments without supersensitivity, but atrophic-appearing segments looked translucent and thin, failing to become denser, even with 1% pilocarpine. CONCLUSIONS: The innervational history and current status of each clock-hour segment of the iris sphincter can be determined using this technique of videographic infrared transillumination, and the progression and pattern of iris denervation and reinnervation can be determined in patients with Adie's pupil. A miotic Adie's pupil that is "tonic," even in darkness, was found to be associated with a dense pattern of infrared transillumination in sphincter segments, which the authors interpret as being associated with a rich reinnervation from accommodative fibers. Segments that become densely reinnervated appear to lose their cholinergic supersensitivity.

The effects of oral contraceptives on delayed onset muscle soreness following exercise.

Several authors have suggested that estrogen may serve to protect skeletal muscle from exercise-induced damage. The present study examined the effects of regularly ingesting estrogen, in the form of oral contraceptives, on postexercise muscle damage following a bench-stepping regimen. Women currently ingesting oral contraceptives (OC) were compared with eumennorheic controls (CG). All subjects performed a 50-min stepping exercise during the midluteal phase of their menstrual cycle. Muscle damage was evaluated on 2, 3, and 5 days postexercise using several established indirect indicators: perceived soreness, strength and range of motion changes, girth measurements, and creatine kinase (CK) activity. Subjects on OC reported significantly lower quadriceps soreness (p < 0.05) relative to the CG (peak soreness = 4.0 and 7.8, respectively, on a scale of 1-10 where 1 is normal and 10 is very, very sore). These results indicate that oral contraceptive use attenuates soreness following an exhaustive stepping activity but cannot support a relationship between estrogen ingestion and other indices of exercise-induced muscle damage.

Evaluation of a significantly shorter version of the Farnsworth-Munsell 100-hue test in patients with three different optic neuropathies.

We tested the hypothesis that a subset of the Farnsworth-Munsell 100-hue test (FM-100) would be a sensitive, specific, and practical means of monitoring color vision in patients with chronic optic nerve disorders. We retrospectively analyzed the records of 1,113 patients affected with optic neuritis (ON), Graves' ophthalmopathy with suspected optic neuropathy, or idiopathic intracranial hypertension with suspected optic neuropathy (IIH). One hundred six records of patients showed that an FM-100 had been performed (23 ON, 46 Graves', 37 IIH). Forty additional patients were studied prospectively (11 ON, 17 Graves', 12 IIH). The sensitivity and specificity of all possible 21 chip subtests were compared against the same statistics for the entire test. We found that for these three optic nerve disorders, a test consisting of chips 22-42 had nearly the same sensitivity and specificity as the entire test when compared with the clinical diagnosis. At 90% specificity, the ratio of sensitivities of the short version to the original version of the test were IIH, 53%/45%; optic neuritis, 85%/79%; and Graves', 67%/70%. The majority of the clinical value of the test can be achieved in one fourth of the original examination time.

C.S. O'Brien: founder of the Department of Ophthalmology, the University of Iowa.

Cecil Starling O'Brien, M.D. (1889-1977), was the founder (1927) of the Department of Ophthalmology at the University of Iowa, and he is credited with the establishment of a strong department that has made many important contributions to ophthalmology. The surviving O'Brien residents were interviewed on videotape, and this article is a composite of their memories together with a brief biographical sketch of Dr. O'Brien.

Drugs and sport. Research findings and limitations.

Many types of drugs are used by athletes to improve performance. This paper reviews the literature on 3 categories of drugs: those that enhance performance as stimulants (amphetamines, ephedrine, and cocaine), those that are used to reduce tremor and heart rate (beta-blockers) and those involved in bodyweight gain or loss (anabolic-androgenic steroids, growth hormone, beta 2-agonists, and diuretics). Limitations of research on these drugs as they relate to performance enhancement are also discussed. The numerous studies that have assessed the effects of amphetamines on performance report equivocal results. This may be due to the large interindividual variability in the response to the drug and the small sample sizes used. Most studies, however, show that some individuals do improve exercise performance when taking amphetamines, which may be attributed to their role in masking fatigue. As a stimulant, ephedrine has not been found to improve performance in the few studies available. More recently, ephedrine has been purported to be effective as a fat burner and used by athletes to maintain or improve muscle mass. Although research on individuals with obesity supports the use of ephedrine for fat loss, no studies have been done on athletes. The few studies of cocaine and exercise suggest that little to no performance gains are incurred from cocaine use. Moreover, the sense of euphoria may provide the illusion of better performance when, in actuality, performance was not improved or was impaired. beta-Blockers have been found to reduce heart rate and tremor and to improve performance in sports that are not physiologically challenging but require accuracy (e.g. pistol shooting). However, there is evidence that some individuals may be high responders to beta-blockers to the extent that their heart rate response is so blunted as to impair performance. Although equivocal, several studies have reported that anabolic-androgenic steroids increase muscle size and strength. However, most studies are not well controlled and use insufficient drug doses. One recent well controlled study did find an increase in muscle mass and strength with supraphysiological doses, and the improvements were greater in participants who were also resistance training. There is little information available on the effects of growth hormone on muscle mass or performance in athletes, although data suggest that growth hormone administration does not increase muscle protein synthesis. beta 2-Agonists, such as clenbuterol and salbutamol, when administered orally appear to improve muscular strength due to their potential role in increasing muscle mass. However, studies have not been done using athletes. Diuretics results in a loss of body water and hence bodyweight that can be advantageous for sports with strict bodyweight classifications. There is insufficient evidence on possible performance decrements in the field that could result from dehydration induced by the diuretics. Overall, the most significant concern in studies of drug use is the large inter-individual variability in responses to a drug. Further studies are needed to understand why some individuals are more responsive than others and to assess whether the responses are consistent for a given individual. Most studies of drug effectiveness have not used athletes. The effectiveness of many drugs may be reduced in highly trained athletes because there is a lower margin for improvement.

Effect of light on the prevalence of simple anisocoria.

PURPOSE: Because simple anisocoria is believed to decrease in bright light, the authors determined the prevalence of simple anisocoria under different lighting conditions. METHODS: The authors measured the pupil size of 104 healthy subjects with infrared videography at four clinically accessible light levels: darkness; darkness with a hand-held light shining from below; room light; and room light with the hand light shining from below. RESULTS: Of the 104 subjects, 40 (38%) were men and 64 (62%) were women. The ages ranged from 12 to 71 years (mean, 36.3 +/- 12.5 years). The mean decrease in pupillary diameter from darkness to the brightest condition was 1.89 mm. Based on the traditional definition of a pupillary diameter difference of 0.4 mm or greater, the prevalence of simple anisocoria decreased from 18% in darkness to 8% in room light with the hand-held light shining from below. The prevalence of anisocoria varied considerably when other definitions were used. Repeated measures analysis of variance showed that pupillary area difference decreased with brighter conditions (P = 0.026). However, the ratio of the pupillary areas did not change with brighter conditions (P = 0.666). CONCLUSIONS: The prevalence of simple anisocoria decreases with brighter conditions based on pupillary diameter difference. However, this decrease is not apparent when anisocoria is expressed as pupillary area ratio. Those clinicians who measure pupils will find that simple anisocoria decreases in bright light. However, with gross observation where perception of an anisocoria may be related more to the ratio of the pupillary areas, simple anisocoria may not seem to change much with brighter conditions.