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Biomedical subjects

C Benson

Publications and source records attributed to C Benson.

At least 19 recordsLinked to original sources

Frequency of anovulation and early menopause among women enrolled in selected adult AIDS clinical trials group studies.

To obtain information on the prevalence of anovulation and early menopause and on pituitary-gonadal function among human immunodeficiency virus type 1-infected women, a study was undertaken that used stored serum samples from women aged 20-42 years who participated in selected Adult AIDS Clinical Trials Group protocols. Defined progesterone and follicle-stimulating hormone (FSH) levels were considered presumptive evidence of ovulation and of menopause, respectively. Anovulation occurred in 16 (48%) of 33 women for whom progesterone levels were tested; early menopause occurred in 2 (8%) of 24 women for whom FSH levels were tested. No statistically significant differences were seen in the demographic and clinical characteristics of anovulatory and ovulatory women, although women who ovulated had higher CD4 T cell counts and were less likely to have reported a recent change in menstrual periods. These data support the findings of prior studies of increased frequency of amenorrhea and/or irregular menstrual cycles, particularly among women with lower CD4 T cell counts.

Acquired Immunodeficiency Syndrome↗

The treatment of advanced renal cell cancer with high-dose oral thalidomide.

Thalidomide is reported to suppress levels of several cytokines, angiogenic and growth factors including TNF-alpha, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). The resulting anti-angiogenic, immunomodulatory and growth suppressive effects form the rationale for investigating thalidomide in the treatment of malignancies. We have evaluated the use of high-dose oral thalidomide (600 mg daily) in patients with renal carcinoma. 25 patients (all men; median age, 51 years; range 34-76 years) with advanced measurable renal carcinoma, who had either progressed on or were not suitable for immunotherapy, received thalidomide in an escalating schedule up to a maximum dose of 600 mg daily. Treatment continued until disease progression or unacceptable toxicity were encountered. 22 patients were assessable for response. 2 patients showed partial responses (9%; 95% CI: 1-29), 7 (32%; 95% CI: 14-55) had stable disease for more than 6 months and a further 5 (23%; 95% CI: 8-45) had stable disease for between 3 and 6 months. We also measured levels of TNF-alpha, bFGF, VEGF, IL-6 and IL-12 before and during treatment. In patients with SD > or = 3 months or an objective response, a statistically significant decrease in serum TNF-alpha levels was demonstrated (P = 0.05). The commonest toxicities were lethargy (> or = grade II, 10 patients), constipation (> or = grade II, 11 patients) and neuropathy (> or = grade II, 5 patients). Toxicities were of sufficient clinical significance for use of a lower and well tolerated dose of 400 mg in currently accruing studies.

Administration, Oral↗

Exponential gain and saturation of a self-amplified spontaneous emission free-electron laser.

Self-amplified spontaneous emission in a free-electron laser has been proposed for the generation of very high brightness coherent x-rays. This process involves passing a high-energy, high-charge, short-pulse, low-energy-spread, and low-emittance electron beam through the periodic magnetic field of a long series of high-quality undulator magnets. The radiation produced grows exponentially in intensity until it reaches a saturation point. We report on the demonstration of self-amplified spontaneous emission gain, exponential growth, and saturation at visible (530 nanometers) and ultraviolet (385 nanometers) wavelengths. Good agreement between theory and simulation indicates that scaling to much shorter wavelengths may be possible. These results confirm the physics behind the self-amplified spontaneous emission process and forward the development of an operational x-ray free-electron laser.

Journal Article↗

Impact of prophylaxis for Mycobacterium avium complex on bacterial infections in patients with advanced human immunodeficiency virus disease.

The epidemiology and natural history of bacterial infections among ambulatory patients with advanced human immunodeficiency virus (HIV) disease has not been well described. In this prospective study, 394 subjects were enrolled and followed at 8-week intervals for a median of 21 months. During follow-up, 164 (42%) of 394 patients developed at least 1 bacterial infection. The most common infections were sinusitis, bacterial pneumonia, skin and soft tissue infection, and bronchitis. Serious bacterial infections (defined as bacterial pneumonia, bacteremia, or deep visceral abscess) were reported by 56 subjects (14%). Female sex, age of <40 years, and Karnofsky score of < or =80 were independent risk factors for bacterial infections. Prophylaxis with clarithromycin, trimethoprim and sulfamethoxazole, or both had significant protective effect. The occurrence of any confirmed bacterial infection was associated with a significantly increased risk of mortality. This study documents that bacterial infections are common among patients with advanced HIV disease, especially among women.

AIDS-Related Opportunistic Infections↗

ABT-378/ritonavir plus stavudine and lamivudine for the treatment of antiretroviral-naive adults with HIV-1 infection: 48-week results.

OBJECTIVE: To evaluate the safety and antiviral activity of different dose levels of the HIV protease inhibitor ABT-378 combined with low-dose ritonavir, plus stavudine and lamivudine in antiretroviral-naive individuals. DESIGN: Prospective, randomized, double-blind, multicenter. METHODS: Eligible patients with plasma HIV-1 RNA > 5000 copies/ml received ABT-378 200 or 400 mg with ritonavir 100 mg every 12 h; after 3 weeks stavudine 40 mg and lamivudine 150 mg every 12 h were added (group I, n = 32). A second group initiated treatment with ABT-378 400 mg and ritonavir 100 or 200 mg plus stavudine and lamivudine every 12 h (group II, n = 68). RESULTS: Mean baseline HIV-1 RNA was 4.9 log10 copies/ml in both groups and CD4 cell count was 398 x 10(6)/l and 310 x 10(6)/l in Groups I and II respectively. In the intent-to-treat (ITT; missing value = failure) analysis at 48 weeks, HIV-1 RNA was < 400 copies/ml for 91% (< 50 copies/ml, 75%) and 82% (< 50 copies/ml, 79%) of patients in groups I and II respectively. Mean steady-state ABT-378 trough concentrations exceeded the wild-type HIV-1 EC50 (effective concentration to inhibit 50%) by 50-100-fold. The most common adverse events were abnormal stools, diarrhea and nausea. No patient discontinued before 48 weeks because of treatment-related toxicity or virologic rebound. CONCLUSIONS: ABT-378 is a potent, well-tolerated protease inhibitor. The activity and durable suppression of HIV-1 observed in this study is probably attributable to the observed tolerability profile and the achievement of high ABT-378 plasma concentrations.

Adult↗

NGO initiatives in risk reduction: an overview.

NGOs appear to be well placed to play a significant role in natural disaster mitigation and preparedness (DMP), working, as they do, with poorer and marginalised groups in society. However, there is little information on the scale or nature of NGO DMP activities. This paper reports the findings of a study seeking to address that gap. It confirms that NGOs are involved in a diverse range of DMP activities but that a number of them are not labelled as such. Moreover, evidence of the demonstrable quality and benefits of DMP involvement is poor. The paper concludes that a number of problems need to be overcome before DMP can be satisfactorily mainstreamed into NGO development and post-disaster rehabilitation programmes. However, there are some early indications of momentum for change.

Developing Countries↗

Outcome of pregnancy after prenatal diagnosis of umbilical vein varix.

Previous studies of umbilical vein varix diagnosed prenatally have been small, and the results have been contradictory. We wanted to determine whether prenatally diagnosed umbilical vein varix is associated with an increased risk of fetal anomalies or poor perinatal outcomes. We identified all cases of fetal intra-abdominal umbilical vein varix diagnosed on the basis of prenatal ultrasonography at Brigham and Women's Hospital between 1988 and 1998. Cases were reviewed to determine the presence of other sonographic findings as well as pregnancy and neonatal outcomes. We identified 25 cases and included those 23 for which follow-up was available. In 11 cases (48%), pregnancies and neonatal outcomes were normal, with full-term delivery, appropriate birth weight, and no evidence of anomalies. Three cases (13%) had preterm deliveries, and 1 had Kell isoimmunization requiring postnatal transfusion. In the remaining 8 cases (35%), structural anomalies were present. One fetus had a chromosomal abnormality (69,XXX). Prenatal diagnosis of fetal umbilical vein varix appears to be associated with a high rate of fetal anomalies. Detection of an umbilical vein varix should prompt a thorough examination of the fetus, including a fetal survey and echocardiogram. Isoimmunization should be ruled out, and consideration of karyotyping should be discussed if other anomalies are present.

Adult↗

Melanoma.

Explore the source record for details and available documents.

Antineoplastic Agents↗

Rifabutin but not clarithromycin prevents cryptosporidiosis in persons with advanced HIV infection.

BACKGROUND: Macrolides have been reported to be effective for the prevention of cryptosporidiosis in persons with HIV infection. OBJECTIVE: To evaluate the efficacy of clarithromycin and rifabutin for the prevention of cryptosporidiosis in persons with advanced HIV infection. DESIGN: Cross-protocol analysis involving 2288 individuals with a history of a CD4 cell counts of < or = 100 x 10(6) cell/l who were enrolled in two prospective clinical trials to prevent Mycobacterium avium complex (MAC) infection and cytomegalovirus (CMV) end-organ disease. INTERVENTIONS: Clarithromycin 500 mg twice daily, rifabutin 300-450 mg daily, the combination of the two or no MAC prophylaxis. MAIN OUTCOME MEASUREMENT: Laboratory-confirmed cryptosporidiosis. Subjects were analyzed in an intent-to-treat and as-treated manner using time-to-event analyses (Cox proportional hazards models). RESULTS: The median length of follow up was 463 days. The median CD4 count at entry was 29 x 10(6) cell/l (range 0-182). There were 60 cases of cryptosporidiosis during the prospective observational period, with an event rate of 2.2 per 100 person-years. In the intent-to-treat [relative risk (RR) 0.50; 95% confidence interval (CI) 0.26-0.96; P = 0.041 and as-treated (RR 0.42; 95% CI 0.20-0.91; P = 0.03) analyses, rifabutin alone was significantly associated with a lower rate of cryptosporidiosis. Clarithromycin alone was not protective in similar analyses (P = 0.98 and 0.90, respectively). CONCLUSIONS: In doses used to prevent MAC infection, rifabutin but not clarithromycin decreases the risk of developing cryptosporidiosis in persons with advanced HIV infection who are not receiving potent combination antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

Observation of self-amplified spontaneous emission and exponential growth at 530 nm

Experimental evidence for self-amplified spontaneous emission (SASE) at 530 nm is reported. The measurements were made at the low-energy undulator test line facility at the Advanced Photon Source, Argonne National Laboratory. The experimental setup and details of the experimental results are presented, as well as preliminary analysis. This experiment extends to shorter wavelengths the operational knowledge of a linac-based SASE free-electron laser and explicitly shows the predicted exponential growth in intensity of the optical pulse as a function of length along the undulator.

Journal Article↗

Parity violation in elastic electron-proton scattering and the Proton's strange magnetic form factor

We report a new measurement of the parity-violating asymmetry in elastic electron scattering from the proton at backward scattering angles. This asymmetry is sensitive to the strange magnetic form factor of the proton as well as electroweak axial radiative corrections. The new measurement of A = -4.92+/-0.61+/-0.73 ppm provides a significant constraint on these quantities. The implications for the strange magnetic form factor are discussed in the context of theoretical estimates for the axial corrections.

Journal Article↗

Neuropeptide FF and FMRFamide potentiate acid-evoked currents from sensory neurons and proton-gated DEG/ENaC channels.

Acidosis is associated with inflammation and ischemia and activates cation channels in sensory neurons. Inflammation also induces expression of FMRFamidelike neuropeptides, which modulate pain. We found that neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe amide) generated no current on their own but potentiated H+-gated currents from cultured sensory neurons and heterologously expressed ASIC and DRASIC channels. The neuropeptides slowed inactivation and induced sustained currents during acidification. The effects were specific; different channels showed distinct responses to the various peptides. These results suggest that acid-sensing ion channels may integrate multiple extracellular signals to modify sensory perception.

Acid Sensing Ion Channels↗

Comparison of gynecologic history and laboratory results in HIV-positive women with CD4+ lymphocyte counts between 200 and 500 cells/microl and below 100 cells/microl.

OBJECTIVE: To assess rates of sexual activity, contraceptive use, genital infections and dysplasia, and other gynecologic symptoms among well-characterized populations of HIV-seropositive women enrolled in two Adult AIDS Clinical Trials Group (AACTG) randomized studies. METHODS: Gynecologic data were collected using standardized interview and examination forms from women enrolled in two protocols: ACTG 175, an antiretroviral trial (CD4+ lymphocyte counts 200-500 cells/microl) and ACTG 196, a Mycobacterium avium complex prophylaxis trial (CD4+ counts < or =100 cells/microl). RESULTS: Women enrolled in the two studies were similar in age, race, weight, and history of illicit or injection drug use, but women in ACTG 196 (n = 67) had lower median CD4+ counts (median, 35 cells/microl; range, 0-135 cells/microl versus median, 356 cells/microl; range, 131-620 cells/microl; p < .0005), were less likely to be antiretroviral naive (6% versus 38%; p < .0005), and were more likely to have a Karnofsky score <80 (28% versus 5%; p < .0001) than women in ACTG 175 (n = 185) at baseline. Recent changes in menstrual cycle were not different between groups. Women enrolled in ACTG 196 were less likely to be sexually active (40% versus 61%; p < .005), but both groups reported high levels of contraceptive use. Papanicolaou smear results in ACTG 196 and ACTG 175 respectively, were: normal, 38% and 50%, atypia, 24% and 39%, low-grade squamous intraepithelial lesions (SIL), 27% and 10%, and high-grade SIL, 11% and 0.7% (p < .001). CONCLUSIONS: Gynecologic complications are common among HIV-seropositive women with CD4+ lymphocyte counts < 500 cells/microl and are more common and severe among those with more advanced immunosuppression.

Adult↗

Analysis of short-term outcome after office-based laser-assisted uvulopalatoplasty.

To determine the short-term effectiveness and outcome of office-based laser-assisted uvulopalatoplasty, a prospective statistically controlled study was done at the Department of Otolaryngology, Cleveland Clinic Florida. Thirty-eight consecutive snoring patients underwent a total of 98 laser-assisted uvulopalatoplasties, and data were gathered through examination, interview, and analog scales of snoring, pain, and other morbidity. In addition, a failure analysis was performed. Data were analyzed by descriptive statistics, confidence intervals, and adjusted analysis of variance (p < 0.008). Our results suggest that snoring decreased significantly around each laser-assisted uvulopalatoplasty treatment performed (4 to 8 weeks apart). Postoperative pain diminished after the first two laser-assisted uvulopalatoplasty treatments. The only morbidity in the series was the result of significant pain, causing 77% of laser-assisted uvulopalatoplasty failures.

Adult↗

A potent activator of HIV-1 replication is present in the genital tract of a subset of HIV-1-infected and uninfected women.

OBJECTIVE AND DESIGN: To determine whether the female genital tract contains factors that affect HIV-1 replication. Cervicovaginal lavage (CVL) samples were collected from HIV-1-seropositive and seronegative women and added to cell cultures. METHODS: HIV p24 production was used to measure the effects of CVL on replication of HIVMN in a T-cell line, of a primary isolate in peripheral blood mononuclear cells, or on HIV expression by the latently-infected monocytic U1 cell line. The effects of CVL on the HIV long terminal repeat (LTR) were determined in 1G5 T cells by measuring luciferase activity. RESULTS: Increased replication of HIVMN and a primary isolate were observed in T cells cultured with CVL samples from three out of 38 HIV-infected women, one out of four uninfected high-risk women, and none of 12 low-risk women. The CVL factor increased replication by enhancing virus expression via activation of the HIV LTR. The HIV-inducing activity was highly stable to heat but was sensitive to proteases, indicating that the activity was distinct from heat-labile cytokines including tumour necrosis factor-alpha. CONCLUSIONS: This is the first study to show that a factor which can stimulate HIV-1 replication is present at biologically active levels in the reproductive tract of women. This factor could potentially affect sexual or vertical transmission of HIV-1 by altering genital tract virus load or virus expression.

Cells, Cultured↗

Infective endocarditis in injection drug users: importance of human immunodeficiency virus serostatus and degree of immunosuppression.

Human immunodeficiency virus (HIV)-infected patients are at increased risk for serious and recurrent bacterial infections. We hypothesized that the degree of immunosuppression may play an important role in outcomes for HIV-seropositive patients with infective endocarditis (IE). To test our hypothesis, we retrospectively reviewed 144 cases of IE in injection drug users. One hundred two patients with documented HIV status (45 HIV-seropositive patients and 57 HIV-seronegative patients) were included in the analysis. Eleven patients (6 HIV-seropositive patients and 5 HIV-seronegative patients) died in the hospital. Staphylococcus aureus, the most common etiologic pathogen causing IE in our series, was isolated from 32 HIV-seropositive patients (71.1%) and 32 HIV-seronegative patients (56.1%). A clear inverse correlation between mortality rate and CD4 cell count was demonstrated (r = -.625; P < .001). Both univariate and multivariate analyses supported the finding of significantly higher mortality rates among patients with CD4 cell counts of < 200/mm3 than among patients with CD4 cell counts of > 500/mm3 (OR, 14.7; 95% CI, 2.64-81.9).

Adult↗