Cognitive effects of short-term use of raloxifene: a randomized clinical trial.

Two questions regarding findings from the Women's Health Initiative are (1) What is the effect of various hormonal regimens including selective estrogen receptor modulators? and (2) Is the negative effect on cognitive functioning related to the older age (65+ years) of the women? This study addresses these two questions in a short-term randomized trial of the effects of raloxifene versus alendronate on cognition. The study found only one significant interaction where the raloxifene and alendronate group changed differently across the two testing occasions. Hence, raloxifene does not have any impact, positive or negative, on short-term cognitive functioning when compared to alendronate.

Mortality following development of breast cancer while using oestrogen or oestrogen plus progestin: a computer record-linkage study.

The literature on the relationship between breast cancer mortality and postmenopausal oestrogen and combined oestrogen/progestin therapy is seemingly contradictory. This study explored survival after exposure to oestrogen or oestrogen plus progestin at or in the year prior to breast cancer diagnosis. Information on patients first diagnosed with invasive breast cancer between 1993 and 1998 was linked with outpatient pharmacy data from 1992 to 2000. Patients were classified according to use of oestrogen alone or oestrogen plus progestin at or in the year prior to diagnosis. Compared to nonusers, and adjusting for age at diagnosis, race/ethnicity, tumour size and grade, oestrogen receptor status, surgery status, and chemotherapy and hormone therapy for breast cancer treatment, oestrogen plus progestin users had lower all-cause mortality (stage I hazard ratio (HR) = 0.69, 95% confidence interval (CI)= 0.48-0.99; stage II HR = 0.53, 95% CI = 0.39-0.72) and breast cancer mortality (stage I HR = 0.52, 95% CI = 0.26-1.04; stage II HR = 0.69, 95% CI = 0.48-0.98). Oestrogen users experienced little or no survival benefit for all-cause mortality (stage I HR = 1.04, 95% CI = 0.77-1.42; stage II HR = 0.86, 95% CI = 0.65-1.14) or breast cancer mortality (stage I HR = 1.23, 95% CI 0.72-2.10; stage II HR = 1.01, 95% CI 0.72-1.41). Our findings suggest, relative to nonusers, a lower risk of death from all causes and from breast cancer in patients who were diagnosed with breast cancer while exposed to oestrogen plus progestin, but not in patients exposed to oestrogen only.

Myocardial infarction risk and tamoxifen therapy for breast cancer.

Tamoxifen prevents recurrence after breast cancer and breast cancer among high-risk women, and may prevent myocardial infarction (MI). To assess the impact of tamoxifen on MI risk, we conducted a case-control study of first MI after breast cancer nested among women diagnosed with breast cancer, while enrolled in a health maintenance organisation from 1980 to 2000. We obtained information on breast cancer treatment and MI risk factors through medical record reviews and interviews. Data were analysed using conditional logistic regression. Of 11,045 women with breast cancer, 134 met MI criteria and were matched to two MI-free control subjects on year of birth and breast cancer diagnosis. After adjusting for smoking, hypertension and diabetes, tamoxifen was unassociated with MI (odds ratio (OR)=1.2, 95% confidence interval (CI)=0.7-1.9). Duration, cumulative dose and recency of use were not associated with MI. Radiation therapy was associated with MI (OR=2.0, 95% CI=1.1-3.5), an association that varied slightly but not statistically significantly by tamoxifen use (radiation with tamoxifen, OR=2.0, 95% CI=0.9-4.4; radiation without tamoxifen, OR=2.9, 95% CI=1.2-7.5). Tamoxifen treatment for breast cancer does not appear to increase or decrease MI risk, although radiation therapy appears to increase MI risk.

Rehospitalisation for neonatal jaundice: risk factors and outcomes.

This case-control study sought to determine whether rehospitalisation for jaundice in newborns is associated with the length of hospital stay after birth and to identify risk factors for and outcomes of rehospitalisation for jaundice. It was carried out among women who delivered a normal, term infant vaginally at any of 10 medical centres from 1992 to 1994. Cases were infants rehospitalised with jaundice within 14 days of birth. Controls were randomly selected from normal, term infants delivered vaginally but not rehospitalised within 90 days of birth. Maternal medical records for pregnancy, labour and delivery care, records for all the birth hospitalisations, and rehospitalisations for the cases were abstracted. The length of birth hospitalisation did not differ between case and control infants, whether length was measured as a categorical variable or as a continuous measure (median = 22.8 h for cases and 23.3 h for controls, P = 0.931). Rehospitalisation for jaundice was associated with race/ethnicity, primiparity, preterm birth, breast feeding and suspicion of jaundice during the birth hospitalisation. None of the rehospitalised infants died, were diagnosed with kernicterus or required resuscitation. Attention to risks associated with jaundice rehospitalisation might reduce this undesirable, but not commonly severe, outcome.

Pneumocystis carinii carriage among cystic fibrosis patients, as detected by nested PCR.

A total of 137 sputa from 95 consecutive cystic fibrosis (CF) patients undergoing routine bacteriological surveillance were analyzed for Pneumocystis carinii colonization using nested PCR. Seven of 95 patients (7.4%) were PCR positive, suggesting that P. carinii carriage may exist among CF patients due to their underlying pulmonary disease.

Triggering the ExoS regulon of Pseudomonas aeruginosa: A GFP-reporter analysis of exoenzyme (Exo) S, ExoT and ExoU synthesis.

The ExoS regulon of Pseudomonas aeruginosa encodes diverse type III secreted effector proteins which have been shown to exert cytotoxic effects in cell culture experiments. However, little information exists about the environmental conditions and stimuli for upregulation of the ExoS regulon. Translational reporter fusion proteins of exoenzyme (Exo) S, ExoT and ExoU, as well as the type II secreted exotoxin A (ETA) to the green fluorescent protein (GFP), were constructed in order to compare exoprotein production under diverse growth conditions. Reporter protein activity was recorded by FACS-analysis and by conventional and confocal laser scanning microscopy. Low ion concentration induced co-ordinated upregulation of ExoS, ExoT and ExoU with a maximum effect at 37 degrees C. A dose-dependent upregulation was seen with human serum or increasing NaCl concentrations. A type III secretion-negative pcrD mutant of P. aeruginosa showed a weak ExoS response to environmental stimuli, compared with the parental strain, suggesting a negative regulatory mechanism. Co-culture with the mammalian cell lines J774A.1 or HeLa led to rapid upregulation of ExoS, ExoT and ExoU synthesis. These data suggest that the ExoS regulon of P. aeruginosa can be triggered by a variety of environmental signals as well as by cell contact with eukaryotic cells.

Specific and rapid detection by fluorescent in situ hybridization of bacteria in clinical samples obtained from cystic fibrosis patients.

We report on the rapid and specific detection of bacteria commonly isolated from clinical specimens from cystic fibrosis (CF) patients by fluorescent in situ hybridization (FISH). On the basis of comparative sequence analysis, we designed oligonucleotide probes complementary to species-specific 16S rRNA regions of these microorganisms and demonstrated the specificities of the probes by hybridization of different remotely related as well as closely related reference strains. Furthermore, in a pilot project we investigated 75 sputum samples and 10 throat swab specimens from CF patients by FISH and detected Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus influenzae, and Staphylococcus aureus within these specimens. The specificity of FISH was 100% in comparison to the results of conventional microbial culture. In contrast, the sensitivity of standard laboratory cultivation was moderately higher, since the limit for microscopic detection of bacteria within sputum samples by FISH was approximately 4 x 10(5) CFU/ml of sputum (resulting in a 90% sensitivity for FISH). Moreover, we demonstrated that FISH will be useful for the rapid detection of bacteria that cause acute pulmonary exacerbations in CF patients, as demonstrated in patients with H. influenzae, S. aureus, and P. aeruginosa exacerbations. Therefore, FISH is a valuable additional method for the rapid and specific detection of bacteria in clinical samples from CF patients, in particular, patients with pulmonary exacerbations.

Evaluation of a breast cancer patient information and support program.

CONTEXT: Women with newly diagnosed breast cancer seek answers to many questions about their disease, treatment options, and prognosis. Failure to meet these needs may cause dissatisfaction with the care process. OBJECTIVE: To evaluate the impact of a support and information program for women with newly diagnosed breast cancer. INTERVENTION: A support and information program that featured a program coordinator, information resources, and mentoring from a breast cancer survivor. DESIGN AND OUTCOME MEASURES: Women in whom breast cancer was diagnosed at program sites (n = 111) and a random sample of women whose breast cancer was diagnosed at nonprogram sites (n = 277) were surveyed by mail to ascertain their level of satisfaction with various aspects of their medical care. The response rates were 74% and 81%, respectively. RESULTS: 75% of women at program sites used the information resources, and 60% requested a patient mentor. Demographic characteristics and satisfaction with non-breast cancer care were almost identical among program and non-program site respondents. For overall breast cancer care, 71% of program site respondents but only 56% of non-program site respondents were very satisfied. More than half of program site respondents rated presurgery care, provision of information, and support received as excellent, versus about 40% of non-program site respondents. Program site respondents were consistently more likely to rate the amount of reassurance and support provided by physicians and nurses as excellent and were less likely to want a second opinion (35% vs. 51%). CONCLUSIONS: The support and information program appears to have had a positive impact on satisfaction with breast cancer care.

Intranasal lidocaine for migraine: a randomized trial and open-label follow-up.

OBJECTIVE: To study the efficacy of intranasal lidocaine for the treatment of migraine when administered by subjects in a nonclinic setting. DESIGN: A 1-month, randomized, controlled, double-blind trial, followed by a 6-month open-label follow-up. SETTING: Ambulatory subjects treating themselves outside of a medical setting. SUBJECTS: One hundred thirty-one adult subjects with migraine, diagnosed according to International Headache Society criteria, were enrolled in the study: 113 treated at least one headache in the controlled trial, and 74 treated at least one headache in the open-label phase. All subjects were members of the Kaiser Permanente Southern California Medical Care Program and were recruited at two urban medical centers. INTERVENTION: Intranasal lidocaine 4% or saline placebo 0.5 mL was dropped into the nostril on the side of the headache, or bilaterally for bilateral headache, according to study protocol. MAIN OUTCOME MEASURES: Trial: percent of headaches relieved to mild or none at 15 minutes and relapse of headache within 24 hours. Open-label: percent of headaches relieved to mild or none at 15 and 30 minutes and relapse within 24 hours. RESULTS: In the controlled trial, headache was relieved within 15 minutes in 34 (35.8%) of 95 subjects treated with 4% intranasal lidocaine compared with 8 (7.4%) of 108 subjects receiving placebo (P < .001). Headaches relapsed in 7 (20.6%) of 34 subjects treated with 4% intranasal lidocaine compared to 0 of 8 placebo subjects (P = .312). In the open-label follow-up, headaches were relieved in 129 (41.2%) of 313 episodes within 15 minutes and in 141 (57.6%) of 245 episodes after 30 minutes. Headaches relapsed in 28 (19.9%) of 140. The response did not diminish over time: 32 (62.8%) of 51 first headaches were relieved at 30 minutes and 10 (71.4%) of 14 seventh headaches were relieved. Relapse occurred in 28 (20%) [corrected] of 129 headaches at a mean time (+/- SD) of 7.4 (+/- 6.6) hours. CONCLUSION: Intranasal lidocaine 4% provides rapid relief of migraine symptoms. For those subjects who do respond, the effect does not diminish over 6-month follow-up.

Vaginal birth after cesarean delivery: an admission scoring system.

OBJECTIVE: To develop a scoring system to predict the likelihood of vaginal birth in patients undergoing a trial of labor after previous cesarean delivery using factors known at the time of hospital admission. METHODS: Trial of labor was attempted in 5022 patients who were assigned randomly to score derivation and score testing groups. Multivariate logistic regression modeling was used in the score derivation group to develop a predictive scoring system for vaginal birth. The scoring system was then applied to the testing group to evaluate its predictive ability. RESULTS: Five variables significantly affected the mode of birth and were incorporated into a weighted scoring system. Rates of successful vaginal birth after cesarean ranged from 49% in patients scoring 0-2 to 95% in patients scoring 8-10. Increasing score was associated linearly with increasing probability of vaginal birth after cesarean. CONCLUSION: Increasing scores correlate with increasing probability of vaginal birth after cesarean. The admission vaginal birth after cesarean scoring system may be useful in counseling patients regarding the option of vaginal birth or repeat cesarean delivery. This information could be particularly valuable for the patient who opts for trial of labor but has second thoughts about her mode of birth when labor begins.

Transmission of uropathogens between sex partners.

Epidemiologic evidence and several case reports suggest that Escherichia coli causing urinary tract infection (UTI) may be transmitted between sex partners. In order to test this hypothesis, urinary, vaginal, and fecal E. coli isolates from 19 women with UTI were compared with E. coli found in random initial voids from their most recent male sex partner. E. coli was isolated from 4 of 19 male sex partners. In each case, the E. coli isolated from the man was identical by pulsed-field gel electrophoresis and bacterial virulence profile to the urinary E. coli from his sex partner.

Passive immunity to infection with Yersinia spp. mediated by anti-recombinant V antigen is dependent on polymorphism of V antigen.

The V antigen is a 37-kDa secreted polypeptide encoded on the 70-kb virulence plasmid of pathogenic Yersinia spp. Besides having regulatory functions, it is known to be a virulence factor and a protective antigen. DNA sequencing of the most common serotypes of human pathogenic Yersinia enterocolitica and Y. pseudotuberculosis revealed that two evolutionary distinct types of V antigen exist in Yersinia spp. One type is represented by Y. enterocolitica serotype 08 strains WA, WA-314, and NCTC 10938 (designated LcrV-YenO8); the other type comprises Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica serotypes O3, O9, and O5,27 (LcrV-Yps). A hypervariable region between amino acids 225 and 232 represents the main difference between the two types. By raising monospecific antisera against both types of V antigen (anti-rVO8 and anti-rVO3), we were able to demonstrate that, in general, passive immunization of mice against a challenge with yersiniae was possible with both anti-Y. enterocolitica V antigen sera. However, anti-V antigen serum was protective only if the immunizing V antigen was the same type as the V antigen produced by the infective strain. The failure of the American V antigen type represented by Y. enterocolitica serotype O8 to protect against Yersinia spp. carrying the other V antigen type (LcrV-Yps) could be an explanation for the presence of plague foci in American countries.

Risk factors for vulvovaginal candidiasis: a case-control study among university students.

Vulvovaginal candidiasis (VVC) is a common inflammatory condition caused by vaginal overgrowth of Candida albicans. Typical symptoms include pruritus and discharge. To test the association between several hypothesized risk factors and VVC, we conducted a case-control study among university students, with both clinic and population controls. Symptomatic, culture-proven VVC was associated with receptive oral sex twice or more in the previous 2 weeks [vs not at all, odds ratio (OR) = 3.5; 95% confidence interval (CI) = 1.7-7.0]; oral contraceptive use (OR = 1.8; 95% CI = 0.95-3.6); spermicide use (OR = 3.3; 95% CI = 1.6-6.8); a prior diagnosis of VVC in the previous year (OR = 3.0; 95% CI = 1.5-5.9); and black (OR = 6.8; 95% CI = 3.1-15) and "other" race (OR = 2.2; 95% CI = 1.0-4.6). Estimates are from a cases vs population controls logistic regression model including all five variables; results for cases vs clinic controls were similar. After adjusting for these factors, many other hypothesized risk factors, such as antibiotic use, menstrual hygiene practices, and vaginal intercourse, had little association with VVC.

An examination of the working case definition of chronic fatigue syndrome.

PURPOSE: Chronic fatigue syndrome (CFS) currently is defined by a working case definition developed under the leadership of the United States Centers for Disease Control and Prevention (CDC) based on a consensus among experienced clinicians. We analyzed the experience from one large center to examine the adequacy of the case definition. PATIENTS AND METHODS: Predefined clinical and laboratory data were collected prospectively from 369 patients with debilitating fatigue, of whom 281 (76%) met the major criteria of the original CDC case definition for CFS: (1) fatigue of at least 6 months' duration, seriously interfering with the patient's life; and (2) without evidence of various organic or psychiatric illnesses that can produce chronic fatigue. The same clinical data were obtained from 311 healthy control subjects and two comparison groups with diseases that can present in a similar fashion; relapsing-remitting multiple sclerosis (n = 25) and major depression (n = 19). RESULTS: All of the minor criteria symptoms from the original CDC case definition distinguished patients with debilitating chronic fatigue from healthy control subjects, and many distinguished the patients with chronic fatigue from the comparison groups with multiple sclerosis and depression: myalgias, postexertional malaise, headaches, and a group of infectious-type symptoms (ie, chronic fever and chills, sore throat, swollen glands in the neck or underarm areas). In addition, two other symptoms not currently part of the case definition discriminated the chronic fatigue patients from the control/comparison groups: anorexia and nausea. Physical examination criteria only infrequently contributed to the diagnosis. Patients meeting the CDC major criteria for CFS also met the minor criteria in 91% of cases. CONCLUSION: Patients meeting the major criteria of the current CDC working case definition of CFS reported symptoms that were clearly distinguishable from the experience of healthy control subjects and from disease comparison groups with multiple sclerosis and depression. Eliminating three symptoms (ie, muscle weakness, arthralgias, and sleep disturbance) and adding two others (ie, anorexia and nausea) would appear to strengthen the CDC case definition of CFS.

Chronic vulvovaginal candidiasis: characteristics of women with Candida albicans, C glabrata and no candida.

INTRODUCTION: Although as many as 5% of all women complain of chronic vulvovaginitis, little is known about these women. They may often be misdiagnosed and the role of vaginal yeast culture in diagnosing vulvovaginal candidiasis (VVC) among them has not been clearly defined. METHODS: To address these deficiencies, we tabulated initial diagnoses among new patients and conducted a medical record-based, unmatched case-control study among women reporting a history of chronic vulvovaginitis (four or more episodes in the past year) at a vulvovaginitis specialty clinic. Clinical presentation and medical history were compared for women who had a positive vaginal yeast culture for either Candida albicans or C glabrata, or who had a negative culture. RESULTS: One-third of the women had no apparent vulvovaginal disease at their initial visit. All women reported similar symptoms, except for an increased prevalence of painful sexual intercourse in women with C albicans (chi 2 p = 0.014 versus women with C glabrata and p < 0.001 versus women with no candida). Women with C glabrata were more likely to be non-white (chi 2 p = 0.071 compared with women with C albicans) and to report an underlying medical condition (chi 2 p < or = 0.001 versus both women with C albicans and women with no candida). Physical examination was normal only in women with no candida. C albicans cases were more likely to have positive potassium hydroxide microscopy (chi 2 p = 0.016) and a pH < or = 4.5 (chi 2 p = 0.011) than were C glabrata cases. CONCLUSIONS: These results suggest that reliance on symptoms and signs alone will result in significant misdiagnosis of chronic vulvovaginitis. Among women with VVC, subtle differences in clinical presentation do not reliably distinguish women with C albicans from those with C glabrata. Our study also indicates that vaginal yeast cultures, while not necessary for every patient, are valuable in confirming negative diagnoses, detecting microscopy false-negatives, and identifying non-C albicans isolates.

The epidemiology of vulvovaginal candidiasis among university students.

Vulvovaginal candidiasis affects approximately 20% of women annually, but it is not well characterized epidemiologically. Of 1027 respondents to two mailed cross-sectional surveys at a large university, 37.5% reported a prior clinical diagnosis of vulvovaginal candidiasis. The frequency of first diagnosis increased rapidly after age 17, with an estimated 54.7% of women experiencing the condition by age 25. In a proportional hazards model of age at first diagnosis, vulvovaginal candidiasis was associated with initiation of sexual activity (rate ratio [RR] = 2.9; 95% confidence interval [CI] = 2.2, 3.8), oral contraceptive use (RR = 1.7; CI = 1.4, 2.2), and White (RR = 3.1; CI = 1.7, 5.7) and Black (RR = 5.9; CI = 3.0, 11.5) race vs Asian.