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Biomedical subjects

M M Holmes

Publications and source records attributed to M M Holmes.

At least 19 recordsLinked to original sources
PubMed2005

Testosterone regulates androgen receptor immunoreactivity in the copulatory, but not courtship, neuromuscular system in adult male green anoles.

Androgens regulate the expression of male reproductive behaviour in diverse vertebrate species, often acting on androgen receptors (AR) to induce structural or functional changes in the nervous system and periphery. Male green anoles possess two sexually dimorphic neuromuscular systems, one controlling throat fan (dewlap) extension, which occurs during courtship, and the other mediating copulatory organ function. Although androgens are required for behavioural activation in both systems, testosterone has differential effects on the neuromuscular morphology. It increases the size of copulatory muscle fibres during the breeding season, but significant effects on dewlap muscle fibre size and motoneurone soma size in either system have not been detected. Corresponding to the lack of testosterone-induced morphological effects in the courtship system, relatively low levels of AR are expressed in the associated motoneurones. The present experiment had two goals, aiming to determine whether: (i) the other courtship and copulatory neuromuscular tissues express AR and (ii) testosterone and/or seasonal environmental changes regulate AR expression. The percentage of AR+ nuclei was evaluated in both the breeding and nonbreeding seasons in gonadally intact adult males (Experiment 1) and in castrated males treated with either testosterone or vehicle (Experiment 2). AR was extensively expressed in the dewlap and copulatory muscles, and in a high percentage of the copulatory motoneurones, but immunoreactivity did not vary across season. Testosterone increased the percentage of AR+ nuclei in the copulatory muscles of both breeding and nonbreeding males but not in the dewlap muscle or copulatory motoneurones. Finally, the target structures for both systems (cartilages and hemipenes) expressed AR in all animals. Therefore, the effects of testosterone on AR immunoreactivity suggest that up-regulation of the receptors may be important for morphological change. However, because all structures investigated in the present experiment expressed AR, the data also indicate that the receptors are involved with other functions.

Animals↗
PubMed2001

High levels of estradiol disrupt conditioned place preference learning, stimulus response learning and reference memory but have limited effects on working memory.

The present study investigated the effects of high levels of estradiol in female rats on four different radial arm maze tasks: the hippocampus-dependent spatial working-reference memory task; the prefrontal cortex-hippocampus dependent delayed win-shift task; the striatum-dependent cued win-stay task; and the amygdala-dependent conditioned place preference task. Ovariectomized female rats were injected daily with either 10 microg of estradiol benzoate or sesame oil vehicle approximately 4 h prior to testing. In Experiment 1, treatment with estradiol disrupted learning on the spatial working-reference memory task by increasing the number of reference memory errors to reach criterion. In Experiment 2, treatment with estradiol had no significant effect on the delayed win-shift task. In Experiment 3, treatment with estradiol resulted in impaired performance on a striatum-dependent cued win-stay task. In Experiment 4, treatment with estradiol impaired the acquisition of a conditioned place-preference task. Taken together these findings suggest that high levels of estradiol inhibit reference memory, stimulus response learning, and amygdala-dependent appetitive conditioning while having little effect on working memory.

Amygdala↗
PubMed2000

Food anticipatory activity and photic entrainment in food-restricted BALB/c mice.

The BALB/c mouse was evaluated as a model for the study of entrainment of circadian rhythms by feeding schedules. Mice were housed in a 12:12-h light-dark (LD) environment with food available for 3-5 h/day (5 h before dark onset). Food anticipatory activity (FAA) rhythms were evident in all mice, ranging from robust in some to weak and variable in others. Advancing transients of the end of nocturnal activity were evident in many cases, culminating in a significant shortening of the main bout of nocturnal activity. Transients and contraction of nocturnal activity were not dependent on the expression of FAA. Following restricted feeding, nocturnal activity expanded by a series of delaying transients. On the first day of constant dark (DD) with ad libitum food access following restricted feeding in LD, the phase from which activity free-ran was advanced by comparison with control tests. Transients, compressed nocturnal activity, and advanced phase of free-run suggest that feeding schedules cause phase advancement of light-entrained rhythms in BALB/c mice. When restricted feeding was imposed in DD, several mice expressed robust FAA concurrent with a free-running activity component. In some cases, free-running rhythms entrained to feeding time, and in other cases, the period of the free run lengthened toward 24 h. These data show that restricted feeding in BALB/c mice can engage a circadian mechanism driving FAA rhythms and can also modulate the phase of photic entrainment, possibly by a direct entraining effect on the light-entrained rhythm. The BALB/c mouse strain, in several respects, appears to be a useful model for the study of scheduled feeding and circadian rhythms.

Animals↗
PubMed2000

Predictors of post-rape medical care in a national sample of women.

BACKGROUND: Rape has a negative impact on physical and mental health, health-related behaviors, and health service utilization. Timely medical care is important for preventive services. METHODS: Cross-sectional data were obtained from a larger 2-year longitudinal study, the National Women's Study (NWS). A total of 3006 adult women participated in the final data collection wave of the NWS. During a structured telephone interview, women who reported a most-recent or only rape incident during adulthood were asked about rape characteristics, reporting to authorities, medical care, and rape-related concerns. The main outcome measures were receipt and timing of medical care received after an adult rape, and factors influencing whether or not medical care was received. RESULTS: Of the sample, 214 (7.1%) had experienced a most-recent or only rape as an adult (aged >/=18), and 56 (26.2%) received rape-related medical care following that incident. The final model multivariable logistic regression indicated that reporting the crime to police or other authorities (odds ratio [OR], 9.45; 95% confidence interval [CI]=3. 34-26.70) and fear of sexually transmitted diseases (OR, 8.61; 95% CI=3.12-23.72) were significant predictors of receipt of post-rape medical care. CONCLUSIONS: One in five victims reported an adult rape to police or other authorities; these women were nine times more likely to receive medical care than those who did not. Public health efforts are needed to increase the proportion of rape victims who receive immediate post-rape medical care.

Adolescent↗
PubMed2000

Adolescents and sexually transmissible diseases.

Sexually transmitted infections are alarmingly common among adolescents in the United States. Behavioral, biologic, and health care access factors place adolescent girls at high risk for many common infections. This population also experiences a disproportionate burden related to the sequelae of STDs. The costs are high for the individual adolescent and for society. Clinicians treating adolescent girls should address the general lack of knowledge about the risks and consequences of STDs. They should be prepared to offer confidential and comprehensive counseling, screening, and treatment according to established guidelines. Office policies that protect adolescent confidentiality are an important component in providing effective care. Adolescence is a period during which lifelong health behaviors are established. It provides a critical opportunity for promoting responsible behaviors and reducing risks through health promotion and prevention strategies.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Behavioral feedback regulation of circadian rhythm phase angle in light-dark entrained mice.

Induced and spontaneous wheel running can alter the phase and period (tau) of circadian rhythms in rodents. The relationship between spontaneous running and the phase angle (psi) of entrainment to 24-h light-dark (LD) cycles was evaluated in C57BL/6j mice. With a wheel freely available, psi was significantly correlated with the absolute (r = 0.32) and relative (r = 0.44) amount of activity during the first 2 h of the activity period. When wheels were locked during the first half of the night in LD and then unlocked in constant dark (DD), mice exhibited a delayed psi and lengthened tau compared with mice that had wheels locked during the second half of the night. In DD, tau correlated negatively with total daily activity. To evaluate if wheel running modulates the phase-resetting actions of LD, phase shifts to light pulses were measured at two time points in DD, when daily activity levels differed by 40%. Phase delays to light were 56% greater when activity levels were lower. However, in a counterbalanced follow-up experiment, phase advances and delays to light pulses were not affected by the availability of wheels, although an effect of time in DD was replicated. Spontaneous activity can regulate psi and tau without altering the response of the pacemaker to light.

Animals↗
PubMed1999

Morphine-induced activity attenuates phase shifts to light in C57BL/6J mice.

Circadian rhythms can be phase shifted and entrained by daily schedules of light and by non-photic stimuli such as locomotor activity. Relatively little is known of how photic and non-photic stimuli interact to regulate circadian phase. Morphine injections were used to examine the effects of locomotor activity on phase shifts to light pulses in mice free-running in constant dark. Morphine injections scheduled early or late in the active period (subjective night) induced hyperactivity, but did not induce phase shifts. Light pulses late in the subjective night induced phase advance shifts that were significantly attenuated (63% smaller, p<0. 01) by pretreatment with morphine. This inhibitory effect of morphine on light-induced phase advances was blocked by preventing mice from running for 6 h after the injections. Light pulses early in the subjective night induced phase delay shifts that were only weakly attenuated (15% smaller, p=0.06) by morphine. These results demonstrate behavioral inhibition of light-induced phase resetting of circadian rhythms in mice, and suggest that the strength of this effect may be phase dependent, although other interpretations are possible.

Animals↗
PubMed1999

A randomized, double-blind, placebo-controlled trial of 5-fluorouracil for the treatment of cervicovaginal human papillomavirus.

OBJECTIVE: To compare intravaginal 5-fluorouracil (5-FU) and placebo for the treatment of cervical and/or vaginal human papillomavirus (HPV). METHODS: A randomized, placebo-controlled trial was performed. Women with HPV detected visually or by Papanicolaou (Pap) test and confirmed by colposcopic biopsy were randomized to receive either intravaginal 5-FU cream or an intravaginal placebo cream. Women with cervical or vaginal intraepithelial neoplasia were excluded. The primary outcome measure was cytologic regression of HPV as determined by Pap test screening 4 to 6 months after treatment. The secondary outcome was cytologic evidence of disease progression at both the 4-6-month and 12-month follow-up evaluations. Data were analyzed using the Chi square test with significance established at P < 0.05. RESULTS: A total of forty patients were randomized, and thirty patients had a follow-up Pap test 4 to 6 months after treatment. Of those patients treated with 5-FU, 28% demonstrated regression of HPV on cytologic evaluation, compared with 69% of those treated with placebo (P < 0.05). Twelve-month follow-up cytology was available from 18 of the study participants. There were no significant differences in the frequency of cytologic progression or regression between groups at 12 months. CONCLUSION: Four to six months post treatment, the use of intravaginal 5-FU for the treatment of cervical or vaginal HPV is associated with a lower rate of regression than the use of placebo.

Administration, Intravaginal↗
PubMed1999

Treating health concerns within the context of childhood sexual assault: a case study.

A cognitive-behavioral treatment package used to treat physical health concerns and fears in a young adult woman with a history of child sexual assault is described. Treatment targeting health concerns was used as an adjunct to treatment for posttraumatic stress disorder (PTSD). Treatment included psychoeducation, systematic desensitization, and stress-innoculation training. The treatment helped reduce the patient's health concerns, including stomach cramps and fear of medical examinations. Theoretical issues underlying treatment of health concerns as related to PTSD avoidance behavior are discussed.

Adult↗
PubMed1998

Follow-up of sexual assault victims.

OBJECTIVES: Our goal was to describe medical findings and health-related concerns of sexual assault victims who returned for follow-up and to assess demographic and assault characteristics of victims who used follow-up services compared to those who did not. STUDY DESIGN: This study is a retrospective cohort analysis involving records from two sources: the acute sexual assault evidentiary examination and the SAFE (Sexual Assault Follow-up Evaluation) Clinic visit. Data were extracted from the records of 389 adolescent and adult victims who reported an acute sexual assault and underwent a complete evidentiary examination between January 1, 1995, and June 30, 1997. Descriptive statistics were generated on demographic and historical information, assault characteristics, and medical and laboratory findings. For the subgroup that presented for follow-up, additional descriptive statistics were generated to describe their interim history, concerns, medical outcomes, treatments, and psychosocial functioning. Chi2 analyses were used to identify differences in the group that returned for follow-up compared with the group that did not. Statistical significance was defined as P < .05. RESULTS: There were no differences in age, race, or perpetrator factors between patients who used follow-up services and patients who did not return to the SAFE Clinic. Similarly, there were no other assault characteristics, relationships, or physical examination findings that were associated with follow-up patterns. A total of 31% (n = 122) of all sexual assault victims returned for a follow-up visit. Physical complaints were reported by 42.6%, but 98.0% had normal findings at a general examination, and 94.8% had a normal result of gynecologic examination. Pregnancy and sexually transmitted diseases, including human immunodeficiency virus, were identified through the follow-up clinic. Since the assault, 49.2% had been sexually active, 10% with multiple partners and 73.3% without consistent condom use. Disturbances in sleep, sexual function, and appetite were commonly reported among victims at follow-up. Numerous assault-related fears were reported. CONCLUSIONS: Among recent rape victims, follow-up rates are low, and there are no factors that correlate with the use of follow-up services. Those who do come in for follow-up have physical complaints and health-related concerns that are related to their recent assault, but most have normal physical findings. Efforts to reach sexual assault victims will require aggressive and innovative strategies to remain in contact with women and girls after rape.

Adolescent↗
PubMed1998

Serotonin and feedback effects of behavioral activity on circadian rhythms in mice.

Wheel running activity can shorten the period (tau) of circadian rhythms in rats and mice. The role of serotonin (5HT), in this effect of behavior on circadian pacemaker function, was assessed by measuring tau during wheel-open and wheel-locked conditions in mice sustaining neurotoxic 5HT lesions directed at the suprachiasmatic nucleus (SCN). Intact mice exhibited a significant lengthening of tau (approximately 10 min) within 3 weeks when running wheels were locked. Mice with immunocytochemically confirmed 5HT depletion showed significantly longer tau than intact mice during wheel access, and did not show a significant change in tau up to 6 weeks after wheels were locked. In these mice, variability of tau across wheel access conditions was similar in magnitude to tau variability in intact mice at two time points without wheel access (+/- 3 min). 5HT-depleted mice also exhibited significantly longer activity periods (alpha), and a significantly delayed peak of activity within alpha. Previous studies show that a delayed peak of activity within alpha is associated with longer tau. Group differences in tau, and apparent failure of wheel-locking to lengthen tau in mice with 5HT lesions, may thus be due to loss of a serotonergic behavioral input pathway to the SCN, or to a lesion-induced change in the waveform of the activity rhythm.

5,7-Dihydroxytryptamine↗
PubMed1996

Rape-related pregnancy: estimates and descriptive characteristics from a national sample of women.

OBJECTIVE: We attempted to determine the national rape-related pregnancy rate and provide descriptive characteristics of pregnancies that result from rape. STUDY DESIGN: A national probability sample of 4008 adult American women took part in a 3-year longitudinal survey that assessed the prevalence and incidence of rape and related physical and mental health outcomes. RESULTS: The national rape-related pregnancy rate is 5.0% per rape among victims of reproductive age (aged 12 to 45); among adult women an estimated 32,101 pregnancies result from rape each year. Among 34 cases of rape-related pregnancy, the majority occurred among adolescents and resulted from assault by a known, often related perpetrator. Only 11.7% of these victims received immediate medical attention after the assault, and 47.1% received no medical attention related to the rape. A total 32.4% of these victims did not discover they were pregnant until they had already entered the second trimester; 32.2% opted to keep the infant whereas 50% underwent abortion and 5.9% placed the infant for adoption; an additional 11.8% had spontaneous abortion. CONCLUSIONS: Rape-related pregnancy occurs with significant frequency. It is a cause of many unwanted pregnancies and is closely linked with family and domestic violence. As we address the epidemic of unintended pregnancies in the United States, greater attention and effort should be aimed at preventing and identifying unwanted pregnancies that result from sexual victimization.

Abortion, Induced↗
PubMed1996

Subdermal contraceptive implant (Norplant) continuation rates among adolescents and adults in a family planning clinic.

STUDY OBJECTIVE: The purpose of this study was to prospectively evaluate the continuation rate of subdermal contraceptive implants (Norplant) among adolescent (< 20 years) and adult (> or = 20 years) women in the clinic population of a tertiary care medical center. DESIGN: Adolescents and adults desiring contraception for greater than a 6-month period were eligible for Norplant insertion. Prior to insertion, personal counseling and extensive education were provided. Following insertion, rapid access, personal counseling, and prompt treatment were provided for complications that occurred. Device removal was available to all individuals at any time upon patient request or if side effects could not be ameliorated. Patient demographic, historical, physical, and follow-up data were entered into a computer data base. RESULTS: Since February 1991, 1800 subdermal contraceptive implants were inserted. Of these 1688 patients were prospectively followed, providing 45,576 women-months of data for analysis. Adolescents comprised 40% of the study population. Over a 50-month period, the cumulative continuation rate for adolescents was 93.6%, and for adults it was 91.1%. The mean duration of use among adolescents was 26.5 months and for adults was 27.6 months. CONCLUSIONS: There was no significant difference between adolescent and adult subdermal contraceptive implant continuation rates for up to 50 months of use. In this patient population, high continuation rates may result from a combination of extensive patient education and intensive surveillance by a well-trained and dedicated multidisciplinary staff. When all patients are enrolled in a program that provides aggressive education and supportive follow-up, age is not a significant factor in continuation rates.

Adolescent↗
PubMed1992

Quantitative increases in surgical house officer clinical activity as the basis for increased work loads in a university hospital.

BACKGROUND: House officer (HO) work loads, particularly work hours, have been the subject of considerable controversy. The hypothesis of this study was that a disproportionate work burden has been placed on HOs in teaching hospitals because of increased obligatory clinical activities and increased educational expectations. METHODS: Factors directly and indirectly affecting care of surgical patients were related to individual HO efforts at the University of Michigan from 1981 to 1991. Data regarding clinical activity and support services were abstracted for analysis from hospital year-end reports, personnel rosters, and educational logs and correlated with the number of surgical HOs. RESULTS: The total numbers of HOs in the Department of Surgery were relatively constant (122 +/- 4) throughout the study interval. Increases that occurred in annual hospital admissions (7615 to 10,651), discharges (7909 to 11,176), clinic visits (53,251 to 86,111), total operations (6789 to 16,526), and operating room hours (24,175 to 62,429) were significant (r greater than 0.9; p less than 0.001 in each category). The acuity of inpatient hospital care increased twofold, as measured by a case mix index, and was accompanied by a 125% increase in the number of surgical intensive care unit beds. During the study period, department of surgery faculty increased 49% (59 to 88), clinical nursing staff increased 118% (821 to 1794), hospital administrative staff increased 59% (2086 to 3320), and hospital support staff increased 53% (4134 to 6342). The number of students in each University of Michigan Medical School class, a group that might defray certain HO work loads, decreased significantly by 16% (226 to 189) during this time (r = -0.76; p less than 0.02). CONCLUSIONS: Disproportionate increases in work demands have been placed on surgical HOs compared with other health care team members during the past decade. Calculated work loads increased from 91.2 hr/wk/HO in 1981 to 110.9 hr/wk/HO in 1991. Balancing the increasing service activities with educational needs of surgical HOs remains a substantial challenge to be addressed by educators.

Employee Performance Appraisal↗
PubMed1990

Efficient solution phase synthesis of [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)- 2-(O-ethyl-D-tyrosine)-4-valine-9-desglycine]arginine vasopressin.

A convergent synthesis of the peptide [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)- 2-(O-ethyl-D-tyrosine)-4-valine-9-desglycine]arginine vasopressin (1), based on the classical solution phase method, was developed. The molecule is assembled by a 3 + 4 coupling via the azide method; then the disulfide bridge is installed by iodine treatment of the bis-acetamidomethyl protected thiols, and the terminal arginine amide added by a 7 + 1 coupling. The method has been used to prepare gram quantities of 1 in more than 98% purity and in 13% yield (based on tetrapeptide intermediate 13) after a single stage purification. The method appears to be particularly suitable for the large scale preparation of 1 and other vasopressin congeners. A novel, albeit low level, transfer of acetamidomethyl group from the sulfur of cysteine to the asparagine amide side-chain was detected following hydrogen chloride treatment of Boc-containing intermediates.

Amino Acid Sequence↗