Search PubMed⌕ Search

Biomedical subjects

S Holman

Publications and source records attributed to S Holman.

At least 19 recordsLinked to original sources
PubMed2006

Cortical excitability and age-related volumetric MRI changes.

OBJECTIVE: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in non-demented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. METHODS: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. RESULTS: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. CONCLUSIONS: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. SIGNIFICANCE: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls.

Aged↗
PubMed2003

Function of a genetically modified human liver cell line that stores, processes and secretes insulin.

An alternative approach to the treatment of type I diabetes is the use of genetically altered neoplastic liver cells to synthesize, store and secrete insulin. To try and achieve this goal we modified a human liver cell line, HUH7, by transfecting it with human insulin cDNA under the control of the cytomegalovirus promoter. The HUH7-ins cells created were able to synthesize insulin in a similar manner to that which occurs in pancreatic beta cells. They secreted insulin in a regulated manner in response to glucose, calcium and theophylline, the dose-response curve for glucose being near-physiological. Perifusion studies showed that secretion was rapid and tightly controlled. Removal of calcium resulted in loss of glucose stimulation while addition of brefeldin A resulted in a 30% diminution of effect, indicating that constitutive release of insulin occurred to a small extent. Insulin was stored in granules within the cytoplasm. When transplanted into diabetic immunoincompetent mice, the cells synthesized, processed, stored and secreted diarginyl insulin in a rapid regulated manner in response to glucose. Constitutive release of insulin also occurred and was greater than regulated secretion. Blood glucose levels of the mice were normalized but ultimately became subnormal due to continued proliferation of cells. Examination of the HUH7-ins cells as well as the parent cell line for beta cell transcription factors showed the presence of NeuroD but not PDX-1. PC1 and PC2 were also present in both cell types. Thus, the parent HUH7 cell line possessed a number of endocrine pancreatic features that reflect the common endodermal ancestry of liver and pancreas, perhaps as a result of ontogenetic regression of the neoplastic liver cell from which the line was derived. Introduction of the insulin gene under the control of the CMV promoter induced changes in these cells to make them function to some extent like pancreatic beta cells. Our results support the view that neoplastic liver cells can be induced to become substitute pancreatic beta cells and become a therapy for the treatment of type I diabetes.

Animals↗
PubMed2002

Epidemiology and natural history of ligase chain reaction detected chlamydial and gonococcal infections.

OBJECTIVES: Ligase chain reaction (LCR) technology has dramatically increased the sensitivity of tests for sexually transmitted infections (STIs). It is unknown whether low copy infections (LCR positive, culture negative) have any clinical consequences. We assessed the clinical significance of untreated low copy Chlamydia trachomatis and Neisseria gonorrhoeae infections in a cohort of sexually active women. METHODS: We studied a cohort of sexually active women followed at 6 month intervals for up to 3 years. Frozen urine specimens from 181 women with negative cultures for C. trachomatis and N. gonorrhoeae who were 'high risk' (defined as being less than 40 years old at baseline, and having either Trichomonas vaginalis at baseline or a history of more than one sexual partner during the 12 months before baseline) were tested for C. trachomatis and N. gonorrhoeae by LCR (Abbott Laboratories, Abbott Park, IL, USA). The specimens from all visits for each person were pooled and LCR was performed on the pool. Laboratory results were linked to clinical information. We also tested all urine samples obtained from patients with a positive culture. RESULTS: 10 additional infections (nine C. trachomatis and one N. gonorrhoeae) were detected with LCR technique. None of the women with low copy infection had evidence of subsequent pelvic inflammatory disease or ectopic pregnancy. Pooling of urine samples resulted in a 47% decline in the number of tests performed. CONCLUSIONS: Additional STIs can be identified when using LCR. Pooling of urine specimens is a cost saving technique for C. trachomatis and N. gonorrhoeae testing.

Adult↗
PubMed2001

Retention of women enrolled in a prospective study of human immunodeficiency virus infection: impact of race, unstable housing, and use of human immunodeficiency virus therapy.

Even though women and people of color represent an increasing proportion of US acquired immunodeficiency syndrome (AIDS) cases, few research studies include adequate representation of these populations. Here the authors describe recruitment and retention of a diverse group of human immunodeficiency virus (HIV)-infected and at risk HIV-uninfected women in a prospective study operating in six sites across the United States. Methods used to minimize loss to follow-up in this cohort are also described. For the first 10 study visits that occurred during a 5-year period between 1994 and 1999, the retention rate of participants was approximately 82%. In adjusted Cox analysis, factors associated with retention among all women were older age, African-American race, stable housing, HIV-infected serostatus, past experience in studies of HIV/AIDS, and site of enrollment. In an adjusted Cox analysis of HIV-infected women, African-American race, past experience in studies of HIV/AIDS, site of enrollment, and reported use of combination or highly active antiretroviral HIV therapy at the last visit were significantly associated with retention. In adjusted Cox analysis of HIV-uninfected study participants, only the site of enrollment was significantly associated with study retention. These results show that women with and at risk for HIV infection, especially African-American women, can be successfully recruited and retained in prospective studies.

Adult↗
PubMed2001

Postnatal cell proliferation and death in a lateralized, gender-related, asymmetric nucleus.

Sexual differentiation and lateralization of neurone number in a discrete forebrain nucleus (SDApc) related to masculine vocal emission, occur contemporaneously in postnatal (P0-P15) gerbils. Stereological estimates of cell proliferation and death during SDApc organization were made by BrdU labelling and pyknosis, respectively. Results confirmed that rates of apoptosis were greater in females and lateralized in males. Immunoreactive BrdU cells, located in the SDApc at P0-P6, with low levels at P15, were not numerically different between the sexes. Only at one age, P0, in males, was a left-right difference seen in BrdU-immunoreactive cell numbers. Microglia, identified by isolectin immunostaining, were numerically similar to BrdU cells. We suggest that apoptosis, rather than neurogenesis, differentiates and lateralizes SDApc organization, and proliferating cells are microglia, phagocytosing debris.

Animals↗
PubMed2001

Prevalence and predictors of skin disease in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: We attempted to determine the prevalence and predictors of skin disease in a cohort of women with and at risk for HIV infection. METHODS: We analyzed baseline data from a multicenter longitudinal study of HIV infection in women. RESULTS: A total of 2018 HIV-infected women and 557 HIV-uninfected women were included in this analysis. Skin abnormalities were reported more frequently among HIV-infected than uninfected women (63% vs 44%, respectively; odds ratio [OR] 2.10; 95% confidence interval [95% CI], 1.74-2.54). Infected women were also more likely to have more than 2 skin diagnoses (OR, 3.27; 95% CI, 1.31-8.16). Folliculitis, seborrheic dermatitis, herpes zoster, and onychomycosis were more common among HIV-infected women (P < .05). Independent predictors of abnormal findings on skin examination in the infected women were African American race (OR, 1.38; 95% CI, 1.07-1.77), injection drug use (OR, 2.74; 95% CI, 2.11-3.57), CD4(+) count less than 50 (OR, 1.68; 95% CI, 1.17-2.42), and high viral loads (100,000-499,999 = OR, 1.77; 95% CI, 1.32-2.37; > 499,999 = OR, 2.15; 95% CI, 1.42-3.27). CONCLUSION: HIV infection was associated with a greater number of skin abnormalities and with specific dermatologic diagnoses. Skin abnormalities were also more common among women with CD4(+) cell depletion or higher viral load.

Adolescent↗
PubMed2001

A case-control study of beliefs and behaviors associated with sexually transmitted disease occurrence in Estonia.

BACKGROUND: Epidemiologic data document rapidly increasing sexually transmitted disease (STD) rates throughout Eastern Europe. GOAL: This case-control study was designed to delineate factors contributing to the STD epidemic in Estonia. STUDY DESIGN: For this study, 189 study participants and 112 control subjects completed a behavioral questionnaire and underwent testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. RESULTS: The prevalence of STDs among the control subjects was 32%. Although the participants believed that condoms prevent STDs, only 17% reported consistent use. Methods believed to prevent transmission included washing the genitals (65%), urinating (26%), douching (35%), and using oral contraceptives (19%). An interaction between sex and travel outside Estonia (odds ratio, 0.1; 95% CI, 0-0.7) reflects the fact that males with STDs were more likely to report travel (46% of participants and 45.5% of control subjects with STD) than were those without STD (16.1% of controls without STD). CONCLUSIONS: STD rates are related to high-risk sexual behavior among males traveling outside of Estonia. Intervention is needed to promote understanding of disease transmission dynamics in this area, and to decrease sexual risk behavior, particularly in the context of travel.

Adolescent↗
PubMed2001

Aneuploidy screening in direct chorionic villus samples by fluorescence in situ hybridisation: the use of commercial probes in a clinical setting.

The results of screening for the common aneuploidies involving chromosomes 13, 18, 21, X and Y by florescent in-situ hybridisation (FISH) in direct preparations from 100 chorionic villus samples from pregnancies between 10 and 20 weeks' gestation are reported. Samples prepared using routine methods and analysed with commercially available probes, accurately detected 12 cases of fetal aneuploidy, all referred because of developmental abnormality. Three of the four cases where chromosome abnormality was detected in cultured villi but not by the direct fluorescence in situ hybridisation (FISH) assay, were due to confined placental mosaicism. No chromosomal anomalies were found in the 20 low risk cases where the referral reason was a familial single gene disorder. We conclude that the FISH assay with commercial probes may act as an accurate and less labour intensive alternative to direct chromosome analysis of chorionic villus samples. In cytogenetically low risk cases its use can obtain a result within the time needed for DNA analysis and avoid the need to set up cultures.

Aneuploidy↗
PubMed2000

Domestic violence and childhood sexual abuse in HIV-infected women and women at risk for HIV.

OBJECTIVES: The purpose of this study was to determine the prevalence and effect of domestic violence and childhood sexual abuse in women with HIV or at risk for HIV infection. METHODS: Participants with HIV or at risk for HIV infection enrolled in the Women's Interagency HIV Study. Childhood sexual abuse; all physical, sexual, and coercive violence by a partner; HIV serostatus; demographic data; and substance use and sexual habits were assessed. RESULTS: The lifetime prevalence of domestic violence was 66% and 67%, respectively, in 1288 women with HIV and 357 uninfected women. One quarter of the women reported recent abuse, and 31% of the HIV-seropositive women and 27% of the HIV-seronegative women reported childhood sexual abuse. Childhood sexual abuse was strongly associated with a lifetime history of domestic violence and high-risk behaviors, including using drugs, having more than 10 male sexual partners and having male partners at risk for HIV infection, and exchanging sex for drugs, money, or shelter. CONCLUSIONS: Our data support the hypothesis of a continuum of risk, with early childhood abuse leading to later domestic violence, which may increase the risk of behaviors leading to HIV infection.

Adolescent↗
PubMed1998

Reproductive health hospitalizations among women with human immunodeficiency virus infections.

OBJECTIVE: Our goal was to determine types of inpatient admissions among human immunodeficiency virus-infected women both before and after the human immunodeficiency virus diagnosis, so that we might outline opportunities for intervention. STUDY DESIGN: A total of 292 human immunodeficiency virus-infected women were interviewed about the reproductive history and prior hospitalizations. A reproductive health hospitalization was defined as either an obstetric admission or a gynecologic admission. Other admissions were categorized as either human immunodeficiency virus related, possibly human immunodeficiency virus related, or not human immunodeficiency virus related. Assignments were made independently by two human immunodeficiency virus specialists. If there was a conflict, a third reviewer was used. RESULTS: In the 10 years before study entry 44.4% of women had at least one obstetric admission, 30.4% had at least one gynecologic admission, 3.1% had at least one human immunodeficiency virus-related admission, 18.1% had at least one admission that was possibly human immunodeficiency virus related, and 13.3% had at least one admission that was not human immunodeficiency virus related. Overall, 226 (77%) women had been admitted to the hospital; of these, 201 (69%) had been admitted for reproductive health reasons. Similar patterns were seen in the year before diagnosis and the time after diagnosis. Reproductive health admissions were more common among women who were younger, who used drugs, and who had higher CD4+ cell counts. CONCLUSION: Women with human immunodeficiency virus infection are often admitted to hospitals for reproductive health reasons before and after the human immunodeficiency virus status is known. Clinicians providing reproductive health care must be actively engaged in efforts to reduce the heterosexual and perinatal transmission of human immunodeficiency virus, to identify human immunodeficiency virus-infected women early in the course of the disease, and to provide ongoing care to human immunodeficiency virus-infected women.

Adult↗
PubMed1997

Vertical transmission of toxoplasma by human immunodeficiency virus-infected women.

OBJECTIVE: Our goal was to determine the frequency of mother-to-child transmission of Toxoplasma gondii from human immunodeficiency virus-infected mothers who are also chronically infected with T. gondii. STUDY DESIGN: One hundred thirty-eight women were entered into a prospective study of human immunodeficiency virus infection in pregnancy. The women were seen at enrollment, during the third, sixth, and eighth months of pregnancy (except those enrolled later in pregnancy or at delivery), at 2 and 6 months post partum, and at 6-month intervals thereafter through 4 years after delivery. Standardized interviews and physical examinations were performed, and blood was drawn at each visit. Toxoplasma serologic testing was performed on the sample drawn earliest in pregnancy; the Sabin-Feldman dye test for immunoglobulin G antibodies and enzyme-linked immunoassays for immunoglobulins M, A, and E were used. Univariate analysis for categoric variables was performed with chi2 and two-tailed Fisher exact tests, and for continuous variables the Student t test was used. Statistical Analysis System procedures were followed. RESULTS: Twenty-eight of 138 (20.2%) women who had positive test results for human immunodeficiency virus had positive findings of the Sabin-Feldman dye test. Serologic status for T. gondii did not correlate with age, immune status, parity, or drug use. One of 27 children born to women who were seropositive for both human immunodeficiency virus and T. gondii (one child's serologic status for T. gondii was unknown) had Sabin-Feldman dye test antibodies beyond age 6 months (3.7%, 95% confidence interval 0.09% to 18.9%). Among the cohort of human immunodeficiency virus-infected mothers the rate of mother-to-child human immunodeficiency virus transmission did not vary with maternal Toxoplasma status. However, with sample sizes of 28 and 110, respectively, for the mothers who were T. gondii seropositive and seronegative, the power to detect a difference in the human immunodeficiency virus transmission rate between these groups would be relatively small. CONCLUSIONS: Transmission of T. gondii from a chronically infected mother can occur in the setting of a human immunodeficiency virus infection, but this is not a common phenomenon. In a small cohort of human immunodeficiency virus-infected women we did not observe its occurrence among those without severe immunocompromise.

Adult↗
PubMed1995

A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression. The Fluoxetine Collaborative Study Group.

Depression in the geriatric population is a frequent, serious, and potentially reversible disorder, yet relatively few blinded, controlled, antidepressant trials have been reported. A number of age related issues complicate safe and effective pharmacotherapy. In a 6-week, double-blind trial in moderately to severely depressed (nonpsychotic) outpatients over age 60, fluoxetine (N = 335) was statistically significantly more efficacious than placebo (N = 336) in overall response (43.9% vs. 31.6%, p = .002) and remission (31.6% vs. 18.6%, p < .001) rates. Analyses of early discontinuations because of an adverse drug event revealed no statistically significantly greater rate with fluoxetine (n = 39; 11.6) than was seen with placebo (n = 29; 8.6%). These results corroborate that major depression in an older population is responsive to antidepressant pharmacotherapy. Specifically, fluoxetine, at a conventional 20-mg dose, was both safe and effective relative to placebo in this special population.

Aged↗
PubMed1995

Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles?

Recent reports of transient neurologic deficits have raised concern about the potential toxicity of single-dose spinal 5% lidocaine in 7.5% dextrose. Two cases of volunteers who experienced minor local sensory deficits after slow (60 s) injections of 2 mL 5% lidocaine via Whitacre needles are described. One case was a result of a double injection because of a "failed" block. It seemed possible that the neurologic deficit in these cases resulted from neurotoxicity associated with maldistribution of local anesthetic. Using an in vitro spinal model, we investigated drug distribution resulting from injections through side-port spinal needles to determine whether the use of these needles could result in high local concentrations of hyperbaric solutions. A spinal canal model was fabricated using human magnetic resonance measurements. The model was placed in a surgical supine position and filled with lactated Ringer's solution to simulate the specific gravity of cerebral spinal fluid at 22 degrees C. A hyperbaric solution of phthalocyanine blue dye and dextrose (SG 1.042), simulating the anesthetic, was injected through three different needles (27-gauge 4 11/16-in. Whitacre, 25-gauge 3 1/2-in. Whitacre, 25-gauge 3 1/2-in. Quincke). Triplicate injections were done at rapid (2 mL/10 s) and slow (2 mL/60 s) rates, with needle side ports oriented in a sacral and cephalad direction. At slow rates of injection, using 27- or 25-gauge sacrally directed Whitacre needles, injections showed evidence of maldistribution with extrapolated peak sacral lidocaine concentrations reaching 2.0%. In contrast, distribution after slow injection through sacrally directed Quincke needles was uniform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Does spinal anesthesia result in a more complete sympathetic block than that from epidural anesthesia?

BACKGROUND: Spinal and epidural injection of local anesthetics are used to produce sympathetic block to diagnose and treat certain chronic pain syndromes. It is not clear whether either form of regional anesthesia produces a complete sympathetic block. Spinal anesthesia using tetracaine has been reported to produce a decrease in plasma catecholamine concentrations. This has not been demonstrated for epidural anesthesia in humans with level of anesthesia below C8. One possible explanation is that spinal anesthesia results in a more complete sympathetic block than epidural anesthesia. To examine this question, a cross-over study was performed in young, healthy volunteers. METHODS: Ten subjects underwent both spinal and epidural anesthesia with lidocaine (plain) on the same day with complete recovery between blocks. By random assignment, spinal anesthesia and epidural anesthesia were induced via lumbar injection. Before and 30 min after local anesthetic injection, a cold pressor test (CPT) was performed. Blood was obtained to determine epinephrine and norepinephrine plasma concentrations at four stages: (1) 20 min after placing peripheral catheters, (2) at the end of a 2-min CPT (before conduction block), (3) 30 min after injection of epidural or spinal lidocaine, and (4) at the end of a second CPT (during anesthesia). Mean arterial pressure, heart rate, noninvasive cardiac index, and analgesia to pin-prick were monitored. RESULTS: Neither spinal nor epidural anesthesia changed baseline resting values of catecholamines or any hemodynamic variable, except heart rate, which was slightly decreased during spinal anesthesia. Median level of analgesia was T4 during spinal and T3 during epidural anesthesia. CPT before conduction block reliably increased heart rate, mean arterial pressure, cardiac index, epinephrine, and norepinephrine. Conduction block attenuated the increase in response to CPT only in mean arterial pressure (spinal and epidural) and cardiac index (spinal only). Neither technique blocked the increase in heart rate, norepinephrine, or epinephrine to CPT. CONCLUSIONS: Spinal anesthesia did not result in a more complete attenuation of the sympathetic response to a CPT than did epidural anesthesia. In response to the CPT, spinal anesthesia blocked the increase in cardiac index, and epidural anesthesia resulted in a decrease in total peripheral resistance compared to the pre-anesthesia state. The differences between the techniques are not significant and are of uncertain clinical implications.

Adult↗
PubMed1994

Synthesis and structure-activity relationships of a series of penicillin-derived HIV proteinase inhibitors: heterocyclic ring systems containing P1' and P2' substituents.

As an extension of our earlier work based upon a single penicillin-derived thiazolidine moiety we have found that the decahydroisoquinoline grouping, also present in Ro 31-8959, is an effective replacement for one of the thiazolidine units in C2 symmetric penicillin-derived dimers. Reaction of racemic epoxide 6 with [3S-[3 alpha, 4a alpha, 8a alpha]]-decahydro-N-(1,1-dimethylethyl)-3- isoquinolinecarboxamide gave diasteroisomers 34a and 34b. The stereochemistry of the hydroxyl grouping of 34a was determined to be (S). Reaction of the amines derived from 34a and 34b with thiazolidine 8a gave 50 and 51, respectively. Compound 50 was a potent inhibitor of HIV proteinase (IC50 = 23 nM) with antiviral activity against HIV-1 in vitro (EC50 C8166 cells = 50 nM). However, a poor pharmacokinetic profile in the dog for compound 50 and its analogues, in keeping with earlier studies on penicillin-derived dimers in three species, precluded their development as potential antivirals.

Amino Acid Sequence↗
PubMed1993

The relationship between social support and stress in adolescent mothers.

This study addressed the questions of whether younger and older adolescent mothers differ in type and amount of stress and social support and whether social support can reduce stress in this population. Research achieves were examined to identify mothers 18 years old and younger who attended a special well-baby clinic during a 1-year period when the Barth questionnaire, a measure of perceived stress, was being collected. There were 62 who had completed at least two or more questionnaires that included a measure of attitude toward the pregnancy, attitudes toward childrearing, attitudes toward the infant, and assessment of social support completed in early infancy. Of these, 47 also completed the Barth questionnaire and 48 had a measure of life event stress in the first year. Compared with senior (age 17 and 18) adolescent mothers, junior mothers (younger than age 17) had significantly more negative attitudes toward the pregnancy (p < .007), less current perceived stress after the baby was born (p < .02), and more social support (p < .002). Path analysis indicated that those who were more anxious during pregnancy got more support even after partialing out the effects of maternal age; but after birth, social support was associated with less stress. Hostile childrearing attitudes contributed to increased stress with a pattern suggesting that those with more hostile attitudes engaged in behavior that contributed directly to making their lives more stressful as well as less effective in obtaining the support they needed.

Adaptation, Psychological↗
PubMed1993

The new face of AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗