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Biomedical subjects

L Fox

Publications and source records attributed to L Fox.

At least 37 records · Page 2Linked to original sources
PubMed1999

Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study.

OBJECTIVE: To prospectively establish the specificity, sensitivity, and positive predictive value (PPV) of a basal 17-hydroxyprogesterone (17-HP) level for the screening of 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) among hyperandrogenic women. DESIGN: Prospective observational trial. SETTING: Tertiary care academic medical centers. PATIENT(S): Eight healthy controls, 20 patients with NCAH, and 284 consecutively seen patients with hyperandrogenism. INTERVENTION(S): All controls and patients with NCAH, and select patients with hyperandrogenism, underwent acute ACTH (1-24) stimulation. MAIN OUTCOME MEASURE(S): Specificity was determined by measuring 17-HP every other day during one menstrual cycle in 8 healthy women with normal ovulation (107 samples). Sensitivity was determined by measuring 17-HP between 7 and 9 A.M. and 3 and 5 P.M. on the same day in 20 patients with genetically confirmed NCAH. The PPV was determined by prospectively measuring 17-HP in 284 consecutively seen hyperandrogenic women at their initial evaluation. The diagnosis of NCAH was established by a stimulated 17-HP level of >10 ng/mL. RESULT(S): Among controls, 17-HP levels of <2, <3, and <4 ng/mL all had a specificity of 100% when obtained in the follicular phase; when obtained in the luteal phase, they had specificities of 53%, 82%, and 82%, respectively. Among patients with NCAH, 17-HP levels of >2, >3, and >4 ng/mL had sensitivities of 100%, 90%, and 90%, respectively, for the detection of the disorder when obtained in the morning, and sensitivities of 95%, 90%, and 85%, respectively, when obtained in the afternoon. Among the 284 consecutively seen hyperandrogenic women, the PPVs of the first and second 17-HP levels were 7.3% and 19% for a cutoff level of >2 ng/mL, 13% and 43% for a cutoff level of >3 ng/mL, and 33% and 40% for a cutoff level of >4 ng/mL, respectively. CONCLUSION(S): A basal 17-HP level is a useful screening tool for NCAH. A cutoff level of 4 ng/mL has maximum specificity and PPV, with little loss in sensitivity if testing is performed in the morning and during the follicular phase. However, a lower cutoff level (e.g., 2 or 3 ng/mL) is preferable if testing is performed at odd hours of the day, as is common in many practices, and maximum sensitivity is desired.

17-alpha-Hydroxyprogesterone↗
PubMed1999

Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points.

Biphasic plasma viral decays were modeled in 48 patients treated with ritonavir, zidovudine, and lamivudine. Estimated first- and second-phase decay rates were d1 as 0.47/day and d2 as 0.04/day. Interpatient differences in both decay rates were significant. The d1 was directly correlated with baseline CD4+, CD4+CD28+, and CD8+CD28+ T lymphocyte counts (P<.05) and inversely correlated with baseline virus load (P=.044) and the magnitude of CD4+ and CD8+ T lymphocyte recovery (P<.01). The d2 was directly correlated with baseline percentage of CD8+ T lymphocytes (P=.023), the CD8+CD38+ cell number (P=.024), and the level of IgG that binds to human immunodeficiency virus (HIV) type 1 gp120 (P=.02). Viral decay rates were not predictive of treatment failure or durability of viral suppression. These exploratory findings are consistent with a model in which immunologic factors contribute to elimination of HIV-infected cells and suggest a dynamic interplay between regulation of HIV expression and lymphocyte activation and recovery.

ADP-ribosyl Cyclase↗
PubMed1999

Thalidomide for the treatment of esophageal aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Disease AIDS Clinical Trials Group.

A multicenter, double-blind, randomized, placebo-controlled clinical trial was conducted to determine the safety and efficacy of thalidomide for treating esophageal aphthous ulceration in persons infected with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients with biopsy-confirmed aphthous ulceration of the esophagus were randomly assigned to receive either oral thalidomide, 200 mg/day, or oral placebo daily for 4 weeks. Eight (73%) of 11 patients randomized to receive thalidomide had complete healing of aphthous ulcers at the 4-week endoscopic evaluation, compared with 3 (23%) of 13 placebo-randomized patients (odds ratio, 13.82; 95% confidence interval, 1.16-823.75; P=.033). Odynophagia and impaired eating ability caused by esophageal aphthae were improved markedly by thalidomide treatment. Adverse events among patients receiving thalidomide included somnolence (4 patients), rash (2 patients), and peripheral sensory neuropathy (3 patients). Thalidomide is effective in healing aphthous ulceration of the esophagus in patients infected with HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: results of AIDS Clinical Trials Group Protocol 315.

Human immunodeficiency virus (HIV)-1 infection is associated with progressive cell-mediated immune deficiency and abnormal immune activation. Although highly active antiretroviral therapy regimens can increase circulating CD4 T lymphocyte counts and decrease the risk of opportunistic complications, the effects of these treatments on immune reconstitution are not well understood. In 44 persons with moderately advanced HIV-1 infection, after 12 weeks of treatment with zidovudine, lamivudine, and ritonavir, plasma HIV-1 RNA fell a median of 2.3 logs (P < .0001). Circulating numbers of naive and memory CD4 T lymphocytes (P < .001), naive CD8 T lymphocytes (P < .004), and B lymphocytes (P < .001) increased. Improved lymphocyte proliferation to certain antigens and a tendency to improvement in delayed-type hypersensitivity also were seen. Dysregulated immune activation was partially corrected by this regimen; however, the perturbed expression of T cell receptor V regions in the CD4 and CD8 T lymphocyte populations was not significantly affected. Ongoing studies will ascertain if longer durations of virus suppression will permit more complete immune restoration.

Adult↗
PubMed1998

Acetaminophen as an adjunct to morphine by patient-controlled analgesia in the management of acute postoperative pain.

UNLABELLED: Opioids play a fundamental role in the management of postoperative pain, but their use is associated with a number of side effects, including nausea and vomiting, sedation, and respiratory depression. Co-administration of a nonopioid has been proposed as a method of reducing opioid intake and minimizing side effects. Sixty-one ASA physical status I and II patients were enrolled in a double-blind, randomized, placebo-controlled, parallel study to investigate the effect of a combination of acetaminophen and morphine after open reduction and internal fixation of acute limb fractures. Patients were randomized to receive either oral acetaminophen (1 g every 4 h) or placebo as an adjuvant to morphine by patient-controlled analgesia (PCA) postoperatively. They were assessed daily for 72 h or until the PCA was discontinued according to standardized guidelines. The outcome variables collected were pain scores (11-point scale), amount of morphine self-administered, duration of PCA use, compliance with study design, incidence of nausea and sedation, and overall patient satisfaction. The acetaminophen group had lower pain scores on Day 1 (2.1 vs 3.3; P = 0.03) and a shorter average duration of PCA use (35.8 vs 45.5 h; P = 0.03). Overall patient satisfaction was also significantly greater in the acetaminophen group (8.7 vs 7.9; P = 0.04). These data suggest that acetaminophen is a useful adjunct to morphine PCA. IMPLICATIONS: This study assesses the benefit of combining two analgesics for the treatment of postoperative pain. Such a combination improves the quality of pain relief and patient satisfaction.

Acetaminophen↗
PubMed1998

Activation of bovine lymphocyte subpopulations by staphylococcal enterotoxin C.

Staphylococcus aureus is a major mastitis-causing pathogen in cattle. The chronic nature of bovine staphylococcal mastitis suggests that some products or components of S. aureus may interfere with the development of protective immunity. One class of molecules that could be involved are superantigens (SAgs). Although a significant number of mastitis isolates produce SAgs, the effect of these molecules on the bovine immune system is unresolved. To determine if immunosuppression caused by SAgs could play a role in pathogenesis, we monitored bovine lymphocytes exposed to staphylococcal enterotoxin C1 (SEC1). Activation of bovine lymphocytes by either SEC1 or concanavalin A (ConA) was influenced by the gammadelta/alphabeta T-cell ratio in the culture. Compared to ConA-induced stimulation, cultures stimulated with SEC1 generated small numbers of CD4+ alphabeta T cells expressing high levels of interleukin-2 receptor alpha chain (IL-2R alpha) and major histocompatibility complex class II (MHCII), suggesting that SAg exposure does not lead to full activation of these cells. This state of partial activation was most pronounced in cultures with a high gammadelta/alphabeta ratio. In contrast, significant numbers of CD8+ alphabeta T cells expressed high levels of IL-2R alpha and MHCII, regardless of the gammadelta/alphabeta ratio and the stimulant used. CD8+ blasts in cultures stimulated with SEC1 also expressed another activation marker, ACT3, previously detected predominantly on thymocytes and CD4+ T cells. Although gammadelta CD2- and CD2+ T cells expressed MHCII and IL-2R alpha following stimulation with SEC1, only a few cells increased to blast size, suggesting that they were only partially activated. The results suggest ways in which SAgs might facilitate immunosuppression that promotes the persistence of bacteria in cattle and contributes to chronic intramammary infection.

Animals↗
PubMed1998

Sexually transmitted diseases are common in women attending Jamaican family planning clinics and appropriate detection tools are lacking.

OBJECTIVES: To assess sexually transmitted diseases (STD) among women attending Jamaican family planning clinics and to evaluate decision models as alternatives to STD laboratory diagnosis. METHODS: Women attending two family planning clinics in Kingston were interviewed and tested for syphilis seroreactivity using toluidine red unheated serum test and Treponema pallidum haemagglutination, for gonorrhoea using culture, for chlamydial infection using enzyme linked immunoassay, and for trichomoniasis using culture. Urine was tested with leucocyte esterase dipstick (LED). The women were treated based upon a clinical algorithm. Computer simulations explored the use of risk inclusive decision models for detection of cervical infection and/or trichomoniasis. RESULTS: Among 767 women, 206 (26.9%) had at least one STD. The prevalence of gonorrhoea was 2.7%; chlamydial infection 12.2%; gonococcal and/or chlamydial cervical infection 14.1%; trichomoniasis 11.5%; syphilis seroreactivity 5.9%. The clinical algorithm was 3.7% sensitive and 96.7% specific in detecting cervical infection. Detection of cervical infection and/or trichomoniasis was 63.5% sensitive and 60.6% specific using LED and 57.7% sensitive and 46.2% specific using the risk inclusive algorithm employed in Jamaican STD clinics. Either cervical friability or LED (+) or family planning clinic attender less than 25 years old with more than one sexual partner in the past year was 72.5% sensitive and 53.3% specific. The positive predictive values of the STD clinic algorithm, LED, and two developed decision models ranged from 25.0% to 33.4% to detect cervical infection and/or trichomoniasis in these women. CONCLUSION: STDs were quite prevalent in these mainly asymptomatic family planning clinic attenders. None of the evaluated decision models can be considered a good alternative to case detection using laboratory diagnosis. Appropriate detection tools are needed. In the meantime, available STD control strategies should be maximised, such as promotion of condom use; adequate treatment of symptomatic STD patients and partners; and education of women and men.

Adult↗
PubMed1997

Preliminary evidence for partial restoration of immune function in HIV type 1 infection with potent antiretroviral therapies: clues from the Fourth Conference on Retroviruses and Opportunistic Diseases.

Critical advances in understanding the pathogenesis and treatment of HIV-1 infection have been made. These include the following: delineation of the replication kinetics of HIV in all stages of disease, underscoring the role of viral replication in disease pathogenesis; development of highly sensitive quantitative assays to determine viral load in infected individuals; and potent new antiretroviral drugs, the availability of which has provided a tool for the investigation of viral pathogenesis and immunopathogenesis, and has permitted the demonstration of the clinical efficacy of combination therapies. The results of studies of potent antiretroviral combination therapies presented at the Fourth Conference on Retroviruses and Opportunistic Infections (January 22-26, 1997, Washington, D.C.) demonstrate that such therapies are capable of at least partially restoring the immune system that is damaged by infection with HIV-1. This includes evidence for the ability of potent therapies to begin to reverse the abnormalities of maturation, activation, and function that are attributable directly or indirectly to the CD4+ helper T lymphocyte population.

Anti-HIV Agents↗
PubMed1997

Thalidomide for the treatment of oral aphthous ulcers in patients with human immunodeficiency virus infection. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.

BACKGROUND: In patients with advanced human immunodeficiency virus (HIV) infection, aphthous ulceration of the mouth and oropharynx can become extensive and debilitating. Preliminary reports suggest that thalidomide may promote the healing of oral aphthous ulcers. METHODS: We performed a double-blind, randomized, placebo-controlled study of thalidomide as therapy for oral aphthous ulcers in HIV-infected patients. The patients received a four-week course of either 200 mg of thalidomide or placebo orally once per day. They were evaluated weekly for the condition of the ulcers, their quality of life, and evidence of toxicity. Assays were performed for plasma tumor necrosis factor alpha (TNF-alpha), soluble TNF-alpha receptors, and HIV RNA. RESULTS: Sixteen of 29 patients in the thalidomide group (55 percent) had complete healing of their aphthous ulcers after four weeks, as compared with only 2 of 28 patients in the placebo group (7 percent; odds ratio, 15; 95 percent confidence interval after adjustment for group sequential testing, 1.8 to 499; unadjusted P<0.001). Pain diminished and ability to eat improved with thalidomide treatment. The adverse effects noted with thalidomide included somnolence and rash (7 patients each), and 6 of the 29 patients discontinued treatment because of toxicity. Thalidomide treatment increased HIV RNA levels (median increase, 0.42 log10 copies per milliliter; increase with placebo, 0.05; P=0.04). With thalidomide treatment there were unexpected increases in the plasma concentrations of TNF-alpha and soluble TNF-alpha receptors. CONCLUSIONS: Thalidomide is an effective treatment for aphthous ulceration of the mouth and oropharynx in patients with HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

A consumer perspective on the family agenda.

The point of view of a mental health researcher who was diagnosed with bipolar disorder when her four children were young is applied to several of the other articles in this section. She comments on various aspects of work with families in which one member has a serious mental illness, raising and discussing issues relevant to consumers, as well as to family members.

Activities of Daily Living↗
PubMed1997

Unexpected interaction of methylphenidate (Ritalin) with anaesthetic agents.

We report difficulty with conscious sedation of a child taking methylphenidate for attention deficit disorder and possible delayed adverse interaction of ketamine and methylphenidate resulting in severe nausea, vomiting and dehydration. The effects of methylphenidate and its potential interactions with anaesthetic agents is discussed. We suggest that anaesthesiologists who provide sedation or anaesthesia to patients receiving methylphenidate be aware of the potential need for high sedative doses and the possibility of undesirable interactions.

Anesthetics, Dissociative↗
PubMed1997

Neurodegeneration of somatostatin-immunoreactive neurons in HIV encephalitis.

Recent studies have suggested that neuronal populations that contain glutamate receptors are vulnerable to damage mediated by the human immunodeficiency virus 1 (HIV-1). Somatostatin-immunoreactive neurons contain, among other elements, glutamate receptors, and might therefore be susceptible to HIV-mediated damage. In order to test this hypothesis, we compared patterns of somatostatin immunoreactivity in the cortex and subcortex of autopsied AIDS cases with and without HIV encephalitis (HIVE). Somatostatin immunoreactivity in the frontal cortex interneurons, hippocampal pyramidal and nonpyramidal cells, and globus pallidus was significantly reduced in HIVE. Radioimmunoassay demonstrated a comparable decrease in somatostatin levels in the neocortex of HIVE cases. The decrease in somatostatin immunoreactivity in the neocortex was inversely correlated with the severity of HIVE and global cognitive performance, but not with the extent of the astroglial reaction. These findings indicate that somatostatin-immunoreactive neurons in the cortex are susceptible to damage mediated by HIV and that deficient functioning of this neuronal population might contribute to the cognitive dysfunction observed in AIDS patients.

Basal Ganglia↗
PubMed1997

An analysis of the determinants of urinary urea and creatinine clearance in patients on continuous peritoneal dialysis.

The relative contribution of urinary volume (UV) and urine-to-plasma concentration ratios for urea (U/PUr) and creatinine (U/PCr) to urinary Kt/V urea (Kt/VU) and urinary uncorrected creatinine clearance (CCrU), respectively, was studied by simple and multiple linear regression analysis in 236 urea kinetic studies and 233 creatinine kinetic studies performed in 135 patients on continuous peritoneal dialysis (CPD). The following simple regressions were obtained: Kt/VU = 0.09 + 0.72 (UV), r = 0.75; Kt/VU = -0.01 + 0.11 (U/PUr), r = 0.55; CCrU = 12.06 + 56.46 + 46.46 (UV), r = 0.62; CCrU = 3.51 + 3.40 (U/PCr), r = 0.58. All r values were significant (p < 0.001). According to these regressions, a loss of 0.2 L/24 hours in UV leads to a loss of 0.15 weekly in Kt/VU and 11.3 L/1.73 m2 weekly in corrected CCrU (approximately 8 L/1.73 m2 weekly in corrected CCrU). By multiple linear regression, (1) Kt/VU = -0.38 + 0.70 (UV) + 0.10 (U/PUr). Standardized coefficients were 0.72 for UV and 0.51 for U/PUr (2) CCrU = -33.36 + 59.83 (UV) + 3.63 (U/PCr). Standardized coefficients were 0.65 for UV and 0.61 for U/PCr. UV is the most important determinant of both urea and creatinine urinary clearances in CPD patients. The contribution of the U/P ratios to the urinary clearances is important, but less than that of UV. The primary dependence of urinary clearances on UV allows the use of UV, which can be easily monitored by patients, as a first approximation index of changing residual renal function in CPD.

Creatinine↗