Biomedical subjects

R Ashley

Publications and source records attributed to R Ashley.

At least 19 recordsLinked to original sources

PubMed2006

Toxicokinetic profile of swainsonine following exposure to locoweed (Oxytropis sericea) in naïve and previously exposed sheep.

AIM: To determine the toxicokinetic profiles of swainsonine (SW) in sheep previously (subacute) and not previously (acute) exposed to locoweed. METHODS: Twenty-nine wethers were stratified by bodyweight (BW; 68.0 (SE 7.6) kg) and randomly assigned to one of six treatments. Treatments were: 0 (n=5), 0.4 (n=5), and 1.6 (n=5) mg SW/kg BW for Trial 1, and 0 (n=4), 0.2 (n=5), and 0.8 (n=5) mg SW/kg BW for Trial 2. Acute exposure in both trials included adaptation to blue grama (Bouteloua gracilis) hay for 14 days and no previous exposure to locoweed (i.e. SW), followed by administration of a single oral dose of SW prepared from an extract of locoweed, in the doses described above. Subacute exposure comprised ingestion of a blue grama and locoweed (428 microg SW/g locoweed) diet for 21 days in Trial 1 and 28 days in Trial 2, followed by removal from locoweed for 5 days, then an oral dose of SW, as above. Quantities of locoweed fed in the diet were adjusted to achieve the dose rates specified for each treatment. Blood samples were collected via jugular venepuncture twice daily for 3 days prior to initial exposure to SW and then every 7 days for the duration of the trials, to monitor serum alkaline phosphatase (Alk-P) and aspartate aminotransferase (AST) activities. For intensive sampling periods, SW was administered immediately following blood sampling at 0 h, and blood samples were collected at hourly intervals from 0-12 h, 3-h intervals from 15-24 h, 6-h intervals from 30-48 h, and 12-h intervals from 60-168 h. Concentrations of SW in serum and locoweed extract were determined using the alpha-mannosidase inhibition assay (detection limit=25 ng/ml). Rates of absorption and elimination of SW from serum were calculated for each animal, using exponential curve fits of the concentration of SW in serum concentration vs time plots. RESULTS: In both trials, SW was detected in serum in all animals exposed to locoweed. Elevated (p<0.05) serum Alk-P and AST activities indicated that subclinical SW intoxication was induced during the subacute exposure phase. Calculated rates of elimination were faster (p<0.001) for the 1.6 vs 0.4 (Trial 1) and 0.8 vs 0.2 (Trial 2) mg SW/kg BW doses. Rates of elimination indicated that, in both trials, SW was removed from serum faster (p<0.06) following acute exposure than subacute exposure. Higher exposure rates to SW resulted in higher concentrations of SW in serum within a trial. CONCLUSIONS: Multiple compartments were involved in the kinetics of SW, and dose and previous exposure altered the toxicokinetics of SW. CLININCAL RELEVANCE: Should the true elimination half-life prove to be as high or higher than the 95 h demonstrated for the treatment using 0.4 mg SW/kg BW in Trial 1, then withdrawal periods for clearing SW from sheep should be >40 days (assuming 10 half-lives to clear the compound).

Administration, Oral↗

PubMed2005

Sewer solids-20 years of investigation.

Knowledge about sewer solids has advanced rapidly in the last few decades due to academic research triggered by an emerging renewed interest from sewer operators. It is now known that sewer solids are implicated in: loss of conveyance; potential for acute and chronic pollution of watercourses and effects inside sewers such as generation of malodorous gases and fabric corrosion. Despite this advance in knowledge, there is much that still needs to be understood, particularly the details of some of the mechanisms of flow-solids interactions, such as deposition, consolidation, erosion, biochemical interactions and processes. The history of knowledge development is outlined and areas where there is a need for further elucidation are highlighted.

History, 20th Century↗

PubMed2005

Investigating the effect of storm events on the particle size distribution in a combined sewer simulator.

The changes in particle size of sewer sediment particles rapidly eroded from a previously deposited sediment bed are described, using a rotating annular flume as a laboratory scale sewer simulator. This is the first time that particle size distributions of eroded sewer sediments from a previously deposited sediment bed have been monitored in such a controlled experimental environment. Sediments from Loenen, The Netherlands and Dundee, UK were used to form deposits in the base of the annular flume (WL Delft Netherlands) with varying conditions for consolidation in order to investigate the effect of changing consolidation time, temperature and sediment type on the amount and size of particles eroded from a bed under conditions of increasing shear. The median size of the eroded particles did not change significantly with temperature, although the eroded suspended solids concentration was greater for the higher temperature under the same shear stresses, indicating a weaker bed deposit. An increase in consolidation time caused an increase in median size of eroded solids at higher bed shear stresses, and this was accompanied by higher suspended solids concentrations. As the shear stress increased, the solids eroded from the bed developed under a longer consolidation time (56 hours) tended towards a broad unimodal distribution, whilst the size distribution of solids eroded from beds developed under shorter consolidation times (18 or 42 hours) retained a bi- or tri-modal distribution. Using different types of sediment in the flume had a marked effect on the size of particles eroded.

Netherlands↗

PubMed2005

Detailed observation and measurement of sewer sediment erosion under aerobic and anaerobic conditions.

A greater understanding of the erosion behaviour of sewer sediments is necessary in order to reliably estimate the amount and nature of the sewer sediments released from deposits in sewers and transported either to waste water treatment plants or discharged into the environment. Research has indicated that microbial activity in sediment can influence the physical release of sediment from in-pipe deposits. This paper reports on a series of erosion tests in which sewer sediments from different sewer networks are kept under different environmental conditions and their resistance to erosion is examined. The erosion tests are carried out under aerobic and anaerobic conditions and two temperatures, one representing ambient sewer temperatures and a lower temperature that significantly suppresses bacterial activity.

Aerobiosis↗

PubMed2003

The nature and pollutant role of solids at the water-sediment interface in combined sewer networks.

Solids at the water-sediment interface in combined sewers are known to be important for pollution potential during storm washout via CSOs. They have been investigated in several studies, but nonetheless, little is known about the origins, build-up, transport and nature of these solids. From a review of current knowledge it is apparent that whilst there is general agreement that these solids are largely organic and have high polluting potential, their modes of transport and definition are not generally agreed upon. It is possible that there may be several "types" of these solids, defined as either: "near bed solids" or "fluid sediments/dense undercurrents", possibly representing transport modes in flows with different ranges of ambient (dry weather) velocities and with differing sewerage layouts. Current knowledge is presented and new ideas for resolving the uncertainties regarding the nature, movement and effects of this material are outlined.

Geologic Sediments↗

PubMed2002

Herpes simplex virus type 1 infection: a sexually transmitted infection of adolescence?

OBJECTIVES: To examine the factors associated with antibodies to herpes simplex virus type 1 (HSV-1). DESIGN: Cross sectional study with HSV-1 antibody testing performed by University of Washington western blot assay. SETTING: Central London STD clinic (1990-1) and central London blood donation centre (1992). PARTICIPANTS: Representative sample of 869 new and rebooked GUM clinic attenders and 1494 consecutive blood donors. RESULTS: The prevalence of HSV-1 antibody among clinic attenders was 60.4% (95% CI 57.0 to 63.7) and among donors was 46.1% (95% CI 43.5 to 48.7). HSV-1 antibody was independently associated with increasing age in both populations (p<0.001). Among clinic attenders, HSV-1 was less common among heterosexual men than women and homosexual men (p<0.005), and was more common among black people (p=0.001) and those of lower socioeconomic status (p=0.05). Among blood donors, being single rather than married was independently associated with HSV-1 infection (p=0.03). Early age at first intercourse was strongly associated with presence of HSV-1 in both populations. The adjusted odds of HSV-1 among GUM clinic attenders was 0.37 (95% CI 0.21 to 0.65) for someone aged 20 at first intercourse compared with someone aged <or=15. Among blood donors, those aged 20 had an adjusted odds of 0.64 (95% CI 0.39 to 1.05) compared with someone aged 15. HSV-1 was not associated with increasing number of lifetime partners after adjustment for other factors. CONCLUSIONS: Genital herpes due to HSV-1 antibody is increasing in the United Kingdom, particularly among young people. In this study we found that HSV-1 was strongly associated with early age of first sexual intercourse, which may reflect the sexual practices of people initiating sex in this age group.

Adolescent↗

PubMed2002

Experience and extensions to the ASM2 family of models.

The development of ASM2 has created a complex model for biological phosphorus removal. Most of the published work on calibrating this model has focused on the design of experiments to maximise information with which to calibrate the model, or the use of hourly data collected around and within an aeration tank. But many sewage works do not collect such data, nor have such instrumentation. The application of ASM2 with sparse data collected at a low frequency, and mostly only input-output, is considered in this paper, based on data collected at a Swedish sewage works. This paper shows that ASM2 can be calibrated with such measurements. This paper also looks at a modification to ASM2d to better handle heterotrophic usage of volatile fatty acids, and the use of this model to study the effects of large increases in in-sewer storage on sewage treatment works. Concern about the generation of large quantities of VFAs, and their effect on the sewage treatment processes, was unfounded.

Calibration↗

PubMed2001

Serologic evidence of herpes simplex virus 1 infection and oropharyngeal cancer risk.

In vitro and animal models suggest that the herpes simplex virus 1 (HSV1) may contribute to the development of oropharyngeal squamous cell carcinoma (OSCC). To determine whether the risk of OSCC is related to infection with HSV1 in humans, we recruited 260 patients from 18 to 65 years old who were newly diagnosed with OSCC between 1990-1995 while residing in three western Washington State counties. For comparison, we recruited at random 445 controls frequency matched to cases on age and sex. Participants completed in-person interviews and provided serum samples that were tested for antibody response to HSV1. After adjusting for sex, cigarette smoking, alcohol consumption, age, and income, HSV1 antibody positivity was associated with a slightly increased risk of OSCC [adjusted odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9-2.0]. The adjusted association between HSV1 antibody positivity and OSCC risk among those who were current cigarette smokers (OR, 4.2; CI, 2.4-7.1) was stronger than would be predicted based on the additive combination of smoking alone (OR, 2.3; CI, 1.2-4.2) and HSV1 seropositivity alone (OR, 1.0; CI, 0.6-1.7). There was suggestive evidence that the association between HSV1 infection and OSCC was similarly modified by evidence of HPV infection but no evidence of effect modification with alcohol consumption. This population-based study suggests that HSV1 may enhance the development of OSCC in individuals who are already at increased risk of the disease because of cigarette smoking or HPV infection.

Adolescent↗

PubMed2001

Effect of condoms on reducing the transmission of herpes simplex virus type 2 from men to women.

CONTEXT: Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted infections in the United States. No prospective study has shown the ability of condoms to reduce transmission of HSV-2. OBJECTIVE: To evaluate risk factors for HSV-2 acquisition and efficacy of condoms in prevention of HSV-2 transmission. DESIGN: Analysis of data from a randomized, double-blind, placebo-controlled trial conducted December 13, 1993, to June 28, 1996, of an ineffective candidate HSV-2 vaccine with 18 months of follow-up. SETTING: Eighteen clinical trial centers in the United States. PARTICIPANTS: A total of 528 monogamous couples discordant for HSV-2 infection, including an HSV-2-susceptible population of 261 men and 267 women. MAIN OUTCOME MEASURE: Acquisition of HSV-2 infection by susceptible partners, compared with those remaining free of HSV-2 with regard to demographic characteristics, sexual activity, and condom use. RESULTS: Twenty-six women (9.7%) vs 5 men (1.9%) acquired HSV-2, for a rate per 10 000 sex acts (episodes of sexual intercourse) of 8.9 vs 1.5, respectively (P<.001). In multivariable analysis, younger age (adjusted hazard ratio [HR] per 5 years, 1.57; 95% confidence interval [CI], 1.22-2.04), seropositivity for HSV-1 and HSV-2 vs HSV-2 alone in the source partner (adjusted HR, 2.34; 95% CI, 1.14-4.82), and more frequent sexual activity (adjusted HR per additional sex act per week, 1.10; 95% CI, 1.01-1.19) were associated with higher risk of HSV-2 acquisition. Condom use during more than 25% of sex acts was associated with protection against HSV-2 acquisition for women (adjusted HR, 0.085; 95% CI, 0.01-0.67) but not for men (adjusted HR, 2.02; 95% CI, 0.32-12.50). Risk of HSV-2 transmission declined from 8.5 per 100 person-years in the initial 150-day interval to 0.9 per 100 person-years in the final 150-day interval (P =.002 for trend), concurrent with a decrease in sexual activity and proportion of sex acts occurring when the source partner had genital lesions. CONCLUSIONS: Condom use offers significant protection against HSV-2 infection in susceptible women. Changes in sexual behavior, correlated with counseling about avoiding sex when a partner has lesions, were associated with reduction in HSV-2 acquisition over time. These data suggest that identification of discordant couples can reduce transmission of HSV-2, especially for heterosexual couples in which the male partner has HSV-2 infection.

Acyclovir↗

PubMed2001

Demographic rather than behavioral risk factors predict herpes simplex virus type 2 infection in sexually active adolescents.

BACKGROUND: Despite the high prevalence of herpes simplex virus type 2 (HSV-2) infection in adults and data indicating that many HSV-2 infections are acquired in late adolescence, the demographic and sexual behavior correlates of HSV-2 infection in high risk adolescents have not been extensively studied. METHODS: Using a cross-sectional design we evaluated serologic evidence of HSV-2 infection in 381 adolescents age 14 to 19 years at an urban sexually transmitted disease clinic and a community clinic. Study enrollment was offered to all patients participating in a project offering free hepatitis B vaccine. Participants were interviewed and blood was drawn for HSV Western blot. RESULTS: Twelve percent [95% confidence interval (CI), 8.6 to 15.1] of 379 adolescents in this study had antibodies to HSV-2. Only 22% of HSV-2-seropositive youth reported a history of herpes. Seropositivity for HSV-2 was significantly associated with African-American race (odds ratio, 2.3; 95% CI 1.1 to 4.8) and female gender (odds ratio, 6.0; 95% CI 2.3 to 15.9); 25% of the African-American girls were HSV-2-seropositive. Self-reported condom use, number of sexual partners in the prior 2 months and history of a sexually transmitted disease did not predict HSV-2 antibody status. CONCLUSIONS: HSV-2 infection among adolescents was prevalent, particularly among African-American girls, and correlated with demographic rather than behavioral variables. As in adults most HSV-2 infections were unrecognized. These data suggest that type-specific serologic testing for HSV-2 infection should be considered in sexually active adolescents. Prevention efforts should target children before initiation of sexual activity.

Adolescent↗

PubMed2001

Biodistribution of radiolabeled [(3)H] CMT-3 in rats.

CMT-3 is a NON-ANTIMICROBIAL tetracycline (TC), chemically modified to enhance its collagenase-inhibitory property. This property is therapeutically useful in treating diseases such as periodontitis, cancer and arthritis. CMT-3 was labeled with tritium [(3)H] at Carbon 7. Four adult male Sprague-Dawley rats (350--400 g body weight) were gavaged once with a mixture of cold CMT-3 and [(3)H] CMT-3 (750 microCi). An additional four rats were gavaged for 2 days with cold CMT-3(15 mg/Kg/day) and on the third day the rats were gavaged with a mixture of cold and [(2)H] CMT-3 (750 microCi); and all 8 rats were placed in the metabolic cages. Blood samples were collected from the tail at multiple intervals from 1--14 hr after [(3)H] CMT-3 administration. At 14 hr, the rats were anesthetized, euthanized and various tissues including visceral organs were removed and weighed. The contents of GI tracts were emptied and added to the fecal pellets and weighed. The urine samples were collected and volume measured. Each tissue or organ was minced finely with scissors and 100 mg of tissue was digested in 1 ml of Tissue-solv (Packard Lab), for 4 hrs at 37 degrees C and each sample was diluted up to 10 ml of distilled water. A 100 microl aliquot was taken and diluted with an equal volume of glacial acetic acid, 10 ml of Atom-lite was added and counted for radioactivity in a liquid scintillation spectrometer. This biodistribution study revealed that over 14 hrs, 54% and 3% of [(3)H] CMT-3 were excreted in the feces and urine, respectively. The serum [(3)H] CMT-3 count reached its maximum value at about 12 hours. The tissues retained the CMTs as follow: muscle (23%); skin (2.41%); bone (1.72%); and the brain retained 0.21% of the label. The radioactive CMT-3 in the visceral organs is as follows: GI tract - its contents (8.9%); heart (0.41%), testis (0.41%); lungs >(0.16%); spleen (0.08%); liver (0.03%); kidneys > (0.02%).

Administration, Oral↗

PubMed2000

Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study.

BACKGROUND: Whether serological evidence of prior infection with Chlamydia pneumoniae, herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) is associated with myocardial infarction (MI) and coronary heart disease (CHD) death remains a source of controversy. METHODS AND RESULTS: We conducted a nested case-control study among participants in the Cardiovascular Health Study, a cohort study of persons aged >/=65 years. Cases experienced an incident MI and CHD death (n=213). Control subjects were matched to cases by age, sex, clinic, year of enrollment, and month of blood draw (n=405). Serum was analyzed for IgG antibodies to C pneumoniae, HSV-1, and CMV. After adjustment for other risk factors, the risk of MI and CHD death was associated with the presence of IgG antibodies to HSV-1 (odds ratio [OR] 2.0, 95% CI 1.1 to 3.6) but was not associated with the presence of IgG antibodies to either C pneumoniae (OR 1.1, 95% CI 0.7 to 1.8) or CMV (OR 1.2, 95% CI 0.7 to 1.9). Although there was little association with low to moderate C pneumoniae antibody titers (</=1:512), high-titer (1:1024) C pneumoniae antibody was associated with an increased risk (OR 2.2, 95% CI 1.1 to 4.4). CONCLUSIONS: Among older adults, the presence of IgG antibodies to HSV-1 was associated with a 2-fold increase in the risk of incident MI and CHD death. For C pneumoniae, only high-titer IgG antibodies were associated with an increased risk of MI and CHD death. The presence of IgG antibodies to CMV was not associated with risk among the elderly.

Adult↗

PubMed2000

The role of external beam irradiation in patients undergoing prostate brachytherapy.

6. From this cohort, a matched-pair analysis was performed to better assess the role of EBT and TIPPB (n = 215). PSA relapse-free survival was based on the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Kaplan-Meier actuarial survival curves were compared to assess various prognostic factors. The median follow-up for all 215 matched patients was 44 months (range, 24-81) with an actuarial PSA relapse-free survival (RFS) at 5 years of 81.1%. Patients treated with EBT and TIPPB had a 5-year PSA RFS of 83.5% whereas patients treated with TIPPB only had a 5-year PSA RFS of 79.4% (p = 0.715)10 ng/ml. Risk group analysis combining PSA, Gleason score, and stage failed to identify any risk group for which the addition of EBT was significant. Analysis of postimplant dosimetry using the dose to 90% of the prostate volume (D90) failed to distinguish any difference between groups. A significant advantage for combining EBT and TIPPB could not be demonstrated in this retrospective matched-pair analysis. These data indicate that the role and rationale of combined treatment in prostate brachytherapy requires better clarification, with a prospective randomized trial.

Journal Article↗

PubMed2000

Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons.

BACKGROUND: Most persons who have serologic evidence of infection with herpes simplex virus (HSV) type 2 (HSV-2) are asymptomatic. Historically, it has been assumed that these persons have less frequent viral reactivation than those with symptomatic infection. METHODS: We conducted a prospective study to investigate genital shedding of HSV among 53 subjects who had antibodies to HSV-2 but who reported having no history of genital herpes, and we compared their patterns of viral shedding with those in a similar cohort of 90 subjects with symptomatic HSV-2 infection. Genital secretions of the subjects in both groups were sampled daily and cultured for HSV for a median of 94 days. RESULTS: HSV was isolated from the genital mucosa in 38 of the 53 HSV-2-seropositive subjects (72 percent) who reported no history of genital herpes, and HSV DNA was detected by the polymerase-chain-reaction assay in cultures prepared from genital mucosal swabs in 6 additional subjects. The rate of subclinical shedding of HSV in the subjects with no reported history of genital herpes was similar to that in the subjects with such a history (3.0 percent vs. 2.7 percent). Of the 53 subjects who had no reported history of genital herpes, 33 (62 percent) subsequently reported having typical herpetic lesions; the duration of their recurrences in these subjects was shorter (median, three days vs. five days; P<0.001) and the frequency lower (median, 3.0 per year vs. 8.2 per year; P<0.001) than in the 90 subjects with previously diagnosed symptomatic infection. Only 1 of these 53 subjects had no clinical or virologic evidence of HSV infection. CONCLUSIONS: Seropositivity for HSV-2 is associated with viral shedding in the genital tract, even in subjects with no reported history of genital herpes.

Adult↗

PubMed2000

Examining the role of neoadjuvant androgen deprivation in patients undergoing prostate brachytherapy.

PURPOSE: To assess the role of neoadjuvant androgen deprivation (NAAD) and transperineal interstitial permanent prostate brachytherapy (TIPPB) using a matched-pair analysis selected from a large cohort of patients undergoing TIPPB. PATIENTS AND METHODS: Six hundred twelve consecutive patients with clinically confined prostate cancer were treated between June 1992, and January 1997, with permanent ultrasound-guided TIPPB with either palladium-103 or iodine-125 as monotherapy or combined with external radiation. Patients with prostate glands >/= 60 g underwent treatment with NAAD before TIPPB to reduce the prostate volume (n = 163). The median duration of NAAD was 3.4 months before TIPPB (range, 1 to 8 months). To assess the benefit of NAAD, a matched-pair analysis was performed. The American Society of Therapeutic Radiology and Oncology Consensus Group definition of prostate-specific antigen (PSA) relapse-free survival (RFS) was used with the added caveat of an absolute increase of >/= 1.0 ng/mL. Differences in pretreatment PSA, Gleason scores, and stage were analyzed by Kaplan-Meier curves and the log-rank test. RESULTS: Two hundred sixty-three patients were matched, with a median follow-up duration of 46 months (range, 24 to 76 months). The actuarial 5-year PSA-RFS rate for all 263 patients is 86.5%. The 5-year PSA-RFS rate for patients treated with NAAD and TIPPB was 87.1% compared with 86.9% for those treated with TIPPB only (P =.935). Subgroup analysis by Gleason score groupings, pretreatment PSA, or stage of disease failed to identify any factors for which androgen ablation was beneficial. CONCLUSION: We were unable to identify any improvement with the addition of NAAD to TIPPB in patients with localized prostate cancer in this retrospective matched-pair analysis. Furthermore, there was no subset for which the addition of NAAD was found to be beneficial. Clarification of the role and duration of NAAD in patients with early-stage prostate cancer will require prospective data.

Adenocarcinoma↗

PubMed1999

Isotope selection for patients undergoing prostate brachytherapy.

PURPOSE: Ultrasound-guided transperineal interstitial permanent prostate brachytherapy (TIPPB) is generally performed with either 103Pd or 125I. The use of 125I for low Gleason score tumors and 103Pd for higher Gleason scores has been suggested based on isotope dose rate and cell doubling time observed in in vitro studies. While many centers follow these isotope selection criteria, other centers have elected to use only a single isotope, regardless of Gleason score. No clinical data have been published comparing these isotopes. This study was undertaken to compare outcomes between 125I and 103Pd in a matched pair analysis for patients undergoing prostate brachytherapy. METHODS AND MATERIALS: Six hundred forty-eight consecutively treated patients with clinically confined prostate cancer underwent TIPPB between June 1992 and February 1997. Five hundred thirty-two patients underwent TIPPB alone, whereas 116 received pelvic external beam irradiation and TIPPB. Ninety-three patients received androgen deprivation therapy prior to TIPPB. The prescribed doses for TIPPB were 160 Gy for 125I (pre-TG43) and 120 Gy for 103Pd. Patients treated with combination therapy received 41.4 or 45 Gy (1.8 Gy/fraction) external beam irradiation followed by a 3- to 5-week break and then received either a 120-Gy 125I or a 90-Gy 103Pd implant. Until November 1994, all patients underwent an 125I implant after which the isotope selection was based on either Gleason score (Gleason score 2-5:125I; Gleason 5-8:103Pd) or isotope availability. A matched pair analysis was performed to assess any difference between isotopes. Two hundred twenty-two patients were matched according to Gleason score, prostate-specific antigen (PSA), and stage. PSA relapse-free survival (PSA-RFS) was calculated based on the American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Group definition of failure. Kaplan-Meier actuarial survival curves were compared to assess differences in pretreatment PSA and Gleason score. RESULTS: Univariate analysis of the 648 patients identified Gleason score, pretreatment PSA value, and stage as significant factors to predict PSA-RFS, but failed to identify isotope selection as significant. To address the significance of isotope selection further, the matched pair groupings were performed. The minimum follow-up for all 222 matched patients is 24 months with a median follow-up of 42 months (24-82). The actuarial PSA-RFS at 5 years for all 222 patients is 86.5%. One hundred eleven of the 222 matched patients received a 103Pd implant with an 87.1% 5-year PSA-RFS. The remaining 111 patients underwent a 125I implant with an 85.9% 5-year PSA-RFS (p = n.s.). Analysis of Gleason score subgroups 2-4, 5-6, and 7-9 failed to show any significant difference in PSA-RFS comparing isotopes. Pretreatment PSA subgroups of < or = 10 or > 10 ng/ml also failed to show any significant difference in PSA-RFS survival comparing isotopes. Analysis of postimplant dosimetry using dose delivered to 90% of the prostate volume (D90) did not identify any difference between the isotope groups. CONCLUSIONS: This matched pair analysis failed to demonstrate a difference for 125I and 103Pd in PSA-RFS for patients undergoing TIPPB. In addition, there were no observed advantages for either 125I or 103Pd in either the low or high Gleason score groups. This data indicates that the role of isotope selection for patients undergoing TIPPB requires further clarification.

Analysis of Variance↗

PubMed1999

Urinary morbidity following ultrasound-guided transperineal prostate seed implantation.

PURPOSE: To assess the urinary morbidity experienced by patients undergoing ultrasound-guided, permanent transperineal seed implantation for adenocarcinoma of the prostate. METHODS AND MATERIALS: Between September 1992 and September 1997, 693 consecutive patients presented with a diagnosis of clinically localized adenocarcinoma of the prostate, and were treated with ultrasound-guided transperineal interstitial permanent brachytherapy (TPIPB). Ninety-three patients are excluded from this review, having received neoadjuvant antiandrogen therapy. TPIPB was performed with 125I in 165 patients and with 103Pd in 435 patients. Patients treated with implant alone received 160 Gy with 125I (pre TG43) or 120 Gy with 103Pd. One hundred two patients received preimplant, pelvic external beam radiation (XRT) to a dose of either 41.4 or 45 Gy because of high-risk features including PSA > or = 10 and/or Gleason score > or = 7. Combined modality patients received 120 Gy and 90 Gy, respectively for 125I or 103Pd. All patients underwent postimplant cystoscopy and placement of an indwelling Foley catheter for 24-48 h. Follow-up was at 5 weeks after implant, every 3 months for the first 2 years, and then every 6 months for subsequent years. Patients completed AUA urinary symptom scoring questionnaires at initial consultation and at each follow-up visit. Urinary toxicity was classified by the RTOG toxicity scale with the following adaptations; grade 1 urinary toxicity was symptomatic nocturia or frequency requiring none or minimal medical intervention such as phenazopyridine; grade 2 urinary toxicity was early obstructive symptomatology requiring alpha-blocker therapy; and grade 3 toxicity was considered that requiring indwelling catheters or posttreatment transurethral resection of the prostate for symptom relief. Log-rank analysis and Chi-square testing was performed to assess AUA score, prostate size, isotope selection, and the addition of XRT as possible prognosticators of postimplant urinary toxicity. The prostate volume receiving 150% of the prescribed dose (V150) was studied in patients to assess its correlation with urinary toxicity. RESULTS: Median follow-up was 37 months (range 6-68). Within the first 60 days, 37.3% of the patients reported grade 1 urinary toxicity, 41% had grade 2, and 2.2% had grade 3 urinary toxicity. By 6 months, 21.4% still reported grade 1 urinary toxicity, whereas 12.8% and 3% complained of grade 2 and 3 urinary difficulties, respectively. Patients with a preimplant AUA score < or = 7 had significantly less grade II toxicity at 60 days compared to those with an AUA score of >7 (32% vs. 59.2%, respectively, p = 0.001). Similarly, prostatic volumes < or = 35 cc had a significantly lower incidence of grade II urinary toxicity (p = 0.001). There was no difference in toxicity regarding the isotope used (p = 0.138 at 60 days, p = 0.45 at 6 months) or the addition of preimplant XRT (p = 0.069 at 60 days, p = 0.84 at 6 months). Twenty-eight patients (4.7%) underwent TURP after 3 isotope half-lives for protracted obstructive symptoms. Five of these men (17%) developed stress incontinence following TURP, but all patients experienced relief of their obstructive symptoms without morbidity at last follow-up. The percent of the prostate receiving 150% of the prescribed dose (V150) did not predict urinary toxicity. CONCLUSIONS: TPIPB is well tolerated but associated with mild to moderate urinary morbidity. Pretreatment prostatic volume and AUA scoring were shown to significantly predict for grade 2 toxicity while the use of preimplant, pelvic XRT and isotope selection did not. Patients undergoing TURP for protracted symptoms following TPIPB did well with a 17% risk of developing stress incontinence. V150 did not help identify patients at risk for urinary morbidity. As transperineal prostate implantation is used more frequently the associated toxicities and the definition of possible pretreatment prognostic factors is necessary to

Aged↗

PubMed1999

Recombinant glycoprotein vaccine for the prevention of genital HSV-2 infection: two randomized controlled trials. Chiron HSV Vaccine Study Group.

CONTEXT: In the last 3 decades, herpes simplex virus type 2 (HSV-2) infection seroprevalence and neonatal herpes have increased substantially. An effective vaccine for the prevention of genital herpes could help control this epidemic. OBJECTIVE: To evaluate the efficacy of a vaccine for prevention of HSV-2 infection. DESIGN: Two randomized, double-blind, placebo-controlled multicenter trials of a recombinant subunit vaccine containing 30 microg each of 2 major HSV-2 surface glycoproteins (gB2 and gD2) against which neutralizing antibodies are directed, administered at months 0, 1, and 6. Control subjects were given a citrate buffer vehicle. Participants were followed up for 1 year after the third immunization. SETTING AND PARTICIPANTS: We enrolled 2393 persons from December 10, 1993, to April 4, 1995, who were HSV-2 and human immunodeficiency virus seronegative. One trial with 18 centers enrolled 531 HSV-2-seronegative partners of HSV-2-infected persons; the other, with 22 centers, enrolled 1862 persons attending sexually transmitted disease clinics. A total of 2268 (94.8%) met inclusion criteria and were included in the analysis with 1135 randomized to placebo and 2012 to vaccine. MAIN OUTCOME MEASURE: Time to acquisition of HSV-2 infection, defined by seroconversion or isolation of HSV-2 in culture during the study period by randomization group. RESULTS: Time-to-event curves indicated a 50% lower acquisition rate among vaccine vs placebo recipients during the initial 5 months of the trial; however, overall vaccine efficacy was 9% (95% confidence interval, -29% to 36%). Acquisition rates of HSV-2 were 4.6 and 4.2 per 100 patient-years in the placebo and vaccine recipients, respectively (P =.58). Follow-up of vaccine recipients acquiring HSV-2 infection showed vaccination had no significant influence on duration of clinical first genital HSV-2 episodes (vaccine, median of 7.1 days; placebo, 6.5 days; P>.10) or subsequent frequency of reactivation (median monthly recurrence rate with vaccine, 0.2; with placebo, 0.3; P>.10). The vaccine induced high levels of HSV-2-specific neutralizing antibodies in vaccinated persons who did and did not develop genital herpes. CONCLUSIONS: Efficient and sustained protection from sexual acquisition of HSV-2 infection will require more than high titers of specific neutralizing antibodies. Protection against sexually transmitted viruses involving exposure over a prolonged period will require a higher degree of vaccine efficacy than that achieved in this study.

Adolescent↗