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Biomedical subjects

M Farley

Publications and source records attributed to M Farley.

At least 19 recordsLinked to original sources

Physical symptoms, posttraumatic stress disorder, and healthcare utilization of women with and without childhood physical and sexual abuse.

For four groups of women: no abuse, physical abuse alone, combined sexual and physical abuse, and unclear about memories of abuse, we examined the associations between childhood sexual and physical abuse, chronic physical symptoms in adulthood, PTSD, and health care utilization. Of a randomly selected sample of 600 adult femalc members of a health maintenance organization, 86 (14%) chose to participate. Women with a history of physical and sexual abuse in childhood reported significantly more cardiovascular, immune, musculoskeletal, neurologic, and reproductive symptoms than those without this history. While the Sexual/Physical Abuse group had the most chronic physical symptoms, medical visits, emergency room visits, prescriptions, and severe PTSD, the Unclear Memory group consistently ranked second on these same measures--higher than either Controls or the Physical Abuse group. Findings underscore the importance of screening for trauma history among patients seen in medical clinics, and the importance for psychotherapists of attending to patients' physical as well as psychological symptoms of childhood trauma.

Adult↗

The pressor response to water drinking in humans : a sympathetic reflex?

BACKGROUND: Water drinking increases blood pressure profoundly in patients with autonomic failure and substantially in older control subjects. The mechanism that mediates this response is not known. METHODS AND RESULTS: We studied the effect of drinking tap water on seated blood pressure in 47 patients with severe autonomic failure (28 multiple system atrophy [MSA], 19 pure autonomic failure patients [PAF]). Eleven older controls and 8 young controls served as control group. We also studied the mechanisms that could increase blood pressure with water drinking. Systolic blood pressure increased profoundly with water drinking, reaching a maximum of 33+/-5 mm Hg in MSA and 37+/-7 in PAF mm Hg after 30 to 35 minutes. The pressor response was greater in patients with more retained sympathetic function and was almost completely abolished by trimethaphan infusion. Systolic blood pressure increased by 11+/-2.4 mm Hg in elderly but not in young controls. Plasma norepinephrine increased in both groups. Plasma renin activity, vasopressin, and blood volume did not change in any group. CONCLUSIONS: Water drinking significantly and rapidly raises sympathetic activity. Indeed, it raises plasma norepinephrine as much as such classic sympathetic stimuli as caffeine and nicotine. This effect profoundly increases blood pressure in autonomic failure patients, and this effect can be exploited to improve symptoms due to orthostatic hypotension. Water drinking also acutely raises blood pressure in older normal subjects. The pressor effect of oral water is an important yet unrecognized confounding factor in clinical studies of pressor agents and antihypertensive medications.

Aged↗

Nevoid basal cell carcinoma syndrome and non-Hodgkin's lymphoma.

Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary disorder with a predilection for numerous basal cell carcinomas in addition to odontogenic keratocysts, palmoplantar pitting, and skeletal malformations. NBCCS has been associated with a number of benign and malignant neoplasms. We report the first case of NBCCS in association with non-Hodgkin's lymphoma.

Basal Cell Nevus Syndrome↗

Variations of the pursestring suture in skin cancer reconstruction.

BACKGROUND: The pursestring suture (PSS) utilizes a circumferentially placed intradermal suture to decrease the size of a defect. Its primary application in dermatologic surgery has been to allow placement of a smaller full-thickness skin graft and to enhance secondary intention wound healing. OBJECTIVE: To present our experience with 3 variations of the PSS. METHODS: The oval defects resulting after surgical excision of cutaneous malignancies were managed with 3 variations of the traditional pursestring technique. These variations included (1) complete closure of the PSS-reduced defect by the placement of traditional interrupted sutures; (2) PSS with the Burow's triangle graft; (3) use of a PSS only part way around an oval defect to avoid distortion of a nearby free margin. RESULTS: In the 7 years of performing these variations of the PSS technique, we have consistently achieved favorable results. CONCLUSION: We report 3 simple-to-use variations of the PSS technique that have been extremely useful in the management of cutaneous malignancies.

Facial Neoplasms↗

Risk factors for invasive pneumococcal disease in children: a population-based case-control study in North America.

OBJECTIVE: To identify risk factors for invasive pneumococcal disease, including penicillin-resistant infections, among children 2 to 59 months of age. DESIGN: Case-control study. PARTICIPANTS: Patients with invasive pneumococcal infections identified by population-based surveillance (n = 187) and controls identified through random-digit telephone dialing (n = 280). OUTCOME MEASURES: Invasive pneumococcal disease was defined as isolation of Streptococcus pneumoniae from a normally sterile site. Patients 2 to 59 months of age who were residents of one of four active surveillance areas were included. S pneumoniae isolates were tested by broth microdilution. Isolates with a minimum inhibitory concentration to penicillin >/=2 microg/mL were considered resistant. RESULTS: Invasive pneumococcal disease was strongly associated with underlying disease and with day care attendance in the previous 3 months. Among 2- to 11-month-olds, current breastfeeding was associated with a decreased likelihood of invasive pneumococcal disease (odds ratio, 0.27; 95% confidence interval: 0.08, 0.90). Penicillin-resistant infections were independently associated with day care attendance, at least one course of antibiotics, and at least one ear infection in the previous 3 months. CONCLUSIONS: This study shows the association of underlying illnesses, day care attendance, and lack of breastfeeding with risk of invasive pneumococcal disease in children. The association of recent antibiotic use and infection with penicillin-resistant S pneumoniae highlights the need to avoid unnecessary antibiotic use in children.

Anti-Bacterial Agents↗

Geocoding and linking data from population-based surveillance and the US Census to evaluate the impact of median household income on the epidemiology of invasive Streptococcus pneumoniae infections.

The emergence of drug-resistant Streptococcus pneumoniae poses new clinical challenges and may also reflect a change in the epidemiology of S. pneumoniae infections. A variety of studies have shown that drug-resistant S. pneumoniae infections are linked to antimicrobial use. It has been hypothesized that persons of high socioeconomic status are at increased risk for a drug-resistant infection because of greater access to antimicrobial drugs. To assess whether median household income is associated with increased risk of penicillin-nonsusceptible S. pneumoniae infections, the authors geocoded and linked data from population-based surveillance for invasive pneumococcal disease with data from the 1990 US Census. Among invasive pneumococcal isolates from Atlanta, Georgia, in 1994, increasing proportions of penicillin-nonsusceptible isolates were associated with higher median household incomes (chi2 for trend, 15.17; p=0.002). Despite higher rates of invasive pneumococcal disease among blacks and persons who resided within lower median household income areas, white patients in areas with higher median household income had a higher risk of being infected with strains that were not susceptible to penicillin (Wilcoxon rank sum, Z=2.66, p=0.008). These findings demonstrated the utility of geocoding and US Census data in describing the epidemiology of drug-resistant S. pneumoniae and also provided more evidence that socioeconomic factors may influence the development of drug resistance.

Adolescent↗

Serum and cerebrospinal fluid pharmacokinetics of intravenous and oral lamivudine in human immunodeficiency virus-infected children.

We studied the pharmacokinetics of intravenously and orally administered lamivudine at six dose levels ranging from 0.5 to 10 mg/kg of body weight in 52 children with human immunodeficiency virus infection. A two-compartment model with first-order elimination from the central compartment was simultaneously fitted to the serum drug concentration-time data obtained after intravenous and oral administration. The maximal concentration at the end of the 1-h intravenous infusion and the area under the concentration-time curve after oral and intravenous administration increased proportionally with the dose. The mean clearance of lamivudine (+/- standard deviation) in the children was 0.53 +/- 0.19 liter/kg/h (229 +/- 77 ml/min/m2 of body surface area), and the mean half-lives at the distribution and elimination phases were 0.23 +/- 0.18 and 2.2 +/- 2.1 h, respectively. Clearance was age dependent when normalized to body weight but age independent when normalized to body surface area. Lamivudine was rapidly absorbed after oral administration, and 66% +/- 25% of the oral dose was absorbed. Serum lamivudine concentrations were maintained above 1 microM for >/=8 h of 24 h on the twice daily oral dosing schedule with doses of >/=2 mg/kg. The cerebrospinal fluid drug concentration measured 2 to 4 h after the dose was 12% (range, 0 to 46%) of the simultaneously measured serum drug concentration. A limited-sampling strategy was developed to estimate the area under the concentration-time curve for concentrations in serum at 2 and 6 h.

Administration, Oral↗

Prostitution, violence, and posttraumatic stress disorder.

One hundred and thirty people working as prostitutes in San Francisco were interviewed regarding the extent of violence in their lives and symptoms of posttraumatic stress disorder (PTSD). Fifty-seven percent reported that they had been sexually assaulted as children and 49% reported that they had been physically assaulted as children. As adults in prostitution, 82% had been physically assaulted; 83% had been threatened with a weapon; 68% had been raped while working as prostitutes; and 84% reported current or past homelessness. We differentiated the types of lifetime violence as childhood sexual assault; childhood physical abuse; rape in prostitution; and other (non-rape) physical assault in prostitution. PTSD severity was significantly associated with the total number of types of lifetime violence (r = .21, p = .02); with childhood physical abuse (t = 2.97, p = .004); rape in adult prostitution (Student's t = 2.77, p = .01); and the total number of times raped in prostitution (Kruskal-Wallace chi square = 13.51, p = .01). Of the 130 people interviewed, 68% met DSM III-R criteria for a diagnosis of PTSD. Eighty-eight percent of these respondents stated that they wanted to leave prostitution, and described what they needed in order to escape.

Adolescent↗

Bacterial meningitis in the United States in 1995. Active Surveillance Team.

BACKGROUND: Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS: Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS: On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS: Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.

Adolescent↗

Estrone sulfatase: probing structural requirements for substrate and inhibitor recognition.

The enzyme-catalyzed desulfation of steroids is a transformation that plays an important role in steroid biosynthesis. Conversion of steroid sulfates to unconjugated steroids may provide a source of steroids for processes such as steroid transport and the growth and proliferation of breast cancer. Steroid sulfatase catalyzes the hydrolysis of 3beta-hydroxysteroid sulfates. To identify structural features important in enzyme-inhibitor interaction, a variety of steroidal and non-steroidal phosphate esters were synthesized and tested as inhibitors of steroid sulfatase activity. We report that the basic structure for enzyme-inhibitor binding does not include the steroid nucleus. Furthermore, the hydrophobicity of the non-steroidal phosphates was determined to be an important factor for optimal inhibition. The monoanionic form of the phosphorylated compounds was found to be the inhibitory species. The best non-steroidal inhibitor of steroid sulfatase activity was n-lauroyl tryamine phosphate with a Ki of 3.6 microM and 520 nM at pH 7.5 and 7.0. The poorest non-steroidal based inhibitor of sulfatase activity was tetrahydronaphthyl phosphate with a Ki of 870 and 360 microM at pH 7.5 and 7.0.

Chromogenic Compounds↗

Somatization, dissociation, and tension-reducing behaviors in psychiatric outpatients.

BACKGROUND: Conceptual and methodological difficulties exist in assessing coping behaviors. METHODS: This study investigated coping behaviors in 102 psychiatric outpatients. We used the Dissociative Experiences Scale, a 17-item posttraumatic stress disorder (PTSD) checklist; 2 measures of somatization (the Wahler Physical Symptom Inventory and the Physical Symptom Questionnaire), and 21 questions about subject involvement in positive and pathologic tension-reducing behaviors. RESULTS: Preliminary data suggest that dissociative symptoms, PTSD-like symptoms, and somatization are associated with a variety of positive and pathologic tension-reducing behaviors. CONCLUSIONS: The results suggest that psychiatric outpatients have an array of coping behavior: some are health-promoting, others are relatively self-destructive.

Adaptation, Psychological↗

Physical symptoms, somatization, and dissociation in women survivors of childhood sexual assault.

This study investigated the relation between history of sexual abuse, somatization, and dissociation in 53 women with a self-reported history of sexual assault in childhood and in 30 women who did not report such a history. Dissociation and reporting of chronic physical symptoms were positively correlated in subjects who had a history of sexual abuse, but this relation did not occur in subjects who reported no history of sexual abuse. The more perpetrators a subject reported, the greater the number of reported chronic physical symptoms. As the age of onset of abuse neared puberty, the more the subjects reported childbirth complications. The relation between somatization and dissociation is discussed.

Adolescent↗

Nursing in Iceland.

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Delivery of Health Care↗

Comparison of virus burden in blood and sequential lymph node biopsy specimens from children infected with human immunodeficiency virus.

BACKGROUND: Lymph nodes serve as reservoirs for the replication of human immunodeficiency virus (HIV) type 1. Comparison of serial measurements of virus burden in lymph nodes and peripheral blood after a change in antiretroviral therapy may provide insights into pathogenic mechanisms and permit a more accurate assessment of a therapeutic response. STUDY DESIGN: Nevirapine was added to the drug regiment of eight children with HIV infection treated with the combination of zidovudine and didanosine who had increasing levels of serum p24 antigen. Lymph node biopsies were performed at entry and after 12 weeks of therapy. RESULTS: Neither CD4 counts nor p24 antigen level correlated with the degree of viremia as measured by ribonucleic acid copy numbers in plasma. Correlations were found between HIV DNA copy number in peripheral blood mononuclear cells and HIV DNA copy number in lymph nodes (p = 0.02), as well as between peripheral blood CD4 counts and lymph node architecture. The HIV signals in the lymph nodes conformed to the anatomic organization of apical light zones in the germinal centers; however, in more advanced disease stages, organized germinal centers disappeared as evidence by a decline in the extent of the follicular dendritic network. CONCLUSIONS: Lymph node biopsies in this small number of HIV-infected children revealed a progressive loss of an organized architecture, especially of the follicular dendritic network. This correlated with a progressive loss of CD4+ cells but not with other measures of disease stage, including viral load, as measured by ribonucleic acid copy numbers.

Antiviral Agents↗

Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group.

The safety, tolerability, pharmacokinetic profile, and preliminary activity of lamivudine (2'-deoxy-3'-thiacytidine), a novel cytidine nucleoside analogue with antiretroviral activity, in human immunodeficiency virus (HIV)-infected children beyond the neonatal period were studied. Ninety children received dosages of 1-20 mg/kg/day. Pharmacokinetic evaluation demonstrated serum and cerebrospinal fluid concentrations that increased proportionally to dose. As of January 1994, 11 children had been withdrawn from study for disease progression and 10 because of possible lamivudine-related toxicity, and 6 had died. CD4 and CD8 cell counts remained stable over 24 weeks in therapy-naive children and decrease slightly in previously treated children. Quantitative immune complex-dissociated p24 antigen and HIV RNA were decreased significantly at 12 and 24 weeks. In vitro resistance to lamivudine was documented in sequential virus isolates from some patients by 12 weeks. Lamivudine was well-tolerated and exhibited virologic activity in children, although future use in children is likely to be in combination antiretroviral regimens.

Adolescent↗

Evaluation of human immunodeficiency virus (HIV) type 1 RNA levels in cerebrospinal fluid and viral resistance to zidovudine in children with HIV encephalopathy.

The amount of human immunodeficiency virus (HIV) type 1 RNA and the presence of a codon 215 mutation indicative of zidovudine resistance were evaluated in cerebrospinal fluid (CSF) and plasma obtained from HIV-1-infected children. The level of HIV-1 RNA in CSF was highest in children with severe encephalopathy (n = 25; median, 430 copies/mL; range, 0-2.2 x 10(5) copies/mL) followed by the moderately encephalopathic (n = 7; median, 330; range, 0-1130) and nonencephalopathic groups (n = 9; median, 0; range, 0-566) (P = .007). There was no correlation between CSF and plasma HIV-1 RNA levels. Five of 7 children with the codon 215 mutation in CSF had a progression of encephalopathy, while all 8 children with wild type codon 215 had improved or stable disease during zidovudine treatment (P = .007). These findings suggest that increased viral replication and emergence of drug-resistant HIV-1 variants within the central nervous system may play a role in progression of HIV encephalopathy.

AIDS Dementia Complex↗