Vitamin B6 catabolism and lung cancer risk: results from the Lung Cancer Cohort Consortium (LC3).

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.

No association between circulating concentrations of vitamin D and risk of lung cancer: an analysis in 20 prospective studies in the Lung Cancer Cohort Consortium (LC3).

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study.

SUMMARY: The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D(3) daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer. INTRODUCTION: This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality. METHODS: WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS). RESULTS: Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38-1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44-0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive. CONCLUSION: Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.

Habitual tea consumption and risk of osteoporosis: a prospective study in the women's health initiative observational cohort.

The purpose of this study was to prospectively investigate associations of habitual drinking of regular tea with bone mineral density and fracture risk. Study participants were a multiethnic postmenopausal cohort (n = 91,465) from the nationwide Women's Health Initiative Observational Study. These women were recruited in the United States and aged 50-79 years at the time of enrollment (1994-1998). The average follow-up time was 4.1 years. Habitual consumption of regular tea was assessed with a structured questionnaire at baseline. Clinical fractures during the follow-up were reported in questionnaires, and hip fractures were further confirmed by reviewing medical records. Bone mineral density measurements were conducted among a subgroup of women (n = 4,979) at three Women's Health Initiative bone mineral density centers using dual-energy x-ray absorptiometry. Multivariate analyses suggested a positive trend of increased total body bone mineral density with tea drinking (p < 0.05). However, results from the Cox proportional hazard models did not show any significant association between tea drinking and the risk of fractures at the hip and forearm/wrist. In conclusion, the results from this study indicate that the effect of habitual tea drinking on bone density is small and does not significantly alter the risk of fractures among the US postmenopausal population.

Risk factors for kidney stones in older women in the southern United States.

BACKGROUND: The occurrence of kidney stones is disproportionate in the southern region of the United States. Risk factors for the occurrence of kidney stones in this geographic area have not been reported previously. METHODS: The Women's Health Initiative (WHI) is an ongoing multicenter clinical investigation of strategies for the prevention of common causes of morbidity and mortality among postmenopausal women. A case-control ancillary study was conducted on 27,410 (white or black) women enrolled in the 9 southern WHI clinical centers. There were 1,179 cases (4.3%) of kidney stones at the baseline evaluation. Risk factors for stone formation were assessed in cases versus age- and race-matched control subjects. RESULTS: Risk factors (univariate) included low dietary potassium (2,404 versus 2,500 mg/day, P = 0.006), magnesium (243 versus 253 mg/day, P = 0.003) and oxalate (330 versus 345 mg/day, P = 0.02) intake, as well as increased body mass index (28.5 versus 27.7 kg/m2, P = 0.001) and a history of hypertension (42% versus 34%, P = 0.001). A slightly lower dietary calcium intake (683 versus 711 mg/day, P = 0.04) was noted in case subjects versus control subjects, but interpretation was confounded by the study of prevalent rather than incident cases. Supplemental calcium intake >500 mg/day was inversely associated with stone occurrence. CONCLUSION: Multivariate risk factors for the occurrence of kidney stones in postmenopausal women include a history of hypertension, a low dietary intake of magnesium, and low use of calcium supplements.

The importance of health insurance as a determinant of cancer screening: evidence from the Women's Health Initiative.

BACKGROUND: Amid current changes in health care access across the United States, the importance of health insurance status and insurance type relative to demographic, actual, and perceived health variables as determinants of screening for breast, colorectal, and cervical cancer is uncertain. This analysis evaluates the hypothesis that health insurance independently predicts cancer screening in the Women's Health Initia tive Observational Study cohort. METHODS: Questionnaire data from 55,278 women en rolled in the Women's Health Initiative Observational Study between September 1994 and February 1997 were analyzed by multiple logistic regression to identify predictors of self-reported mammography within 2 years, Pap smear within 3 years, and stool guaiac or flexible sigmoidoscopy within 5 years. RESULTS: Positive determinants of reporting cancer screening were age, ethnic origin, household income, educational level, family history of cancer, having a usual care provider, time since last provider visit, and insurance status and type. Smoking, diabetes, and, among older women, prior cardiovascular events were negative determinants of cancer screening. Among women younger than 65, lacking health insurance or having fee-for-service insurance was strongly associated with failure to report cancer screening, independently of having or using a usual care provider and of demographics, self-perceived health, and health characteristics. Among women 65 and older, those with Medicare alone were less likely, whereas those with Medicare + prepaid insurance were more likely, to report cancer screening. CONCLUSIONS: In the Women's Health Initiative Obser vational Study, a large, diverse group of older women, health insurance type and status were among the most important determinants of cancer screening indepen dent of demographics, chronic health conditions, and self-perceived health characteristics.

Biological variability of serum and urinary N-telopeptides of type I collagen in postmenopausal women.

Measurement of N-telopeptides of type I bone collagen (NTX) provides a specific indicator of the current level of bone resorption. The biological intrasubject variability of NTX in urine and serum was studied in 277 postmenopausal women, mean age, 63.6 years +/- 10.2 (+/-SD) years. Second-morning void urine and serum specimens were collected at baseline and for two consecutive days to determine short-term variability (% CV). Long-term variability was determined by comparing NTX results at baseline and two consecutive months. Subjects were instructed to maintain current diet, lifestyle, and medications during the study. The median short-term %CV was 13.1% for urine NTX. This compared with 6.3% for serum NTX. Calculation of long-term %CV showed similar trends, with the %CV for NTX measured in serum (7.5%) lower than when measured in urine (15.6%). Using the least significant change (LSC) calculation, our data show that to be 90% confident that a decrease in NTX after initiation of antiresorptive therapy in an individual patient is not caused by variability alone, a 31 % decrease in urine NTX and a 14% decrease in serum NTX is required. As reported changes in NTX caused by antiresorptive therapy are greater than these calculations; our results support the use of either specimen to measure NTX to monitor the effect of therapy.

Niacin treatment increases plasma homocyst(e)ine levels.

BACKGROUND: Studies have reported high levels of plasma homocyst(e)ine as an independent risk factor for arterial occlusive disease. The Cholesterol Lowering Atherosclerosis Study reported an increase in plasma homocyst(e)ine levels in patients receiving both colestipol and niacin compared with placebo. Thus the objective of this study was to examine the effect of niacin treatment on plasma homocyst(e)ine levels. METHODS: The Arterial Disease Multiple Intervention Trial, a multicenter randomized, placebo-controlled trial, examined the effect of niacin compared with placebo on homocyst(e)ine in a subset of 52 participants with peripheral arterial disease. RESULTS: During the screening phase, titration of niacin dose from 100 mg to 1000 mg daily resulted in a 17% increase in mean plasma homocyst(e)ine level from 13.1 +/- 4.4 micromol/L to 15.3 +/- 5.6 micromol/L (P <.0001). At 18 weeks after randomization, there was an absolute 55% increase from baseline in mean plasma homocyst(e)ine levels in the niacin group and a 7% decrease in the placebo group (P =.0001). This difference remained statistically significant at the end of follow-up at 48 weeks. CONCLUSIONS: Niacin substantially increased plasma homocyst(e)ine levels, which could potentially reduce the expected benefits of niacin associated with lipoprotein modification. However, plasma homocyst(e)ine levels can be decreased by folic acid supplementation. Thus further studies are needed to determine whether B vitamin supplementation to patients undergoing long-term niacin treatment would be beneficial.

Compliance to multiple interventions in a high risk population.

PURPOSE: Assess compliance with study medications and examine reasons for noncompliance. Individuals with peripheral arterial disease present the clinician with a unique combination of symptoms and therapeutic needs; the treatment of this population has not been adequately studied. METHODS: The Arterial Disease Multiple Intervention Trial was a randomized double-blind placebo-controlled trial that randomized 468 participants to a combination of antioxidants, niacin and warfarin or matching placebos. Men and women (mean age 65 yrs) with peripheral arterial disease and low-density lipoprotein (LDL) < 190 mg/dl were enrolled and followed for one year. Compliance to the study medications was measured by pill count for each medication. An overall measure of compliance was determined by combining pill counts from all study visits. RESULTS: Mean overall pill counts ranged from 88 to 94% in the eight treatment groups. No statistically significant differences were found in mean pill counts over time or between active and placebo groups. History of coronary artery disease and number of follow-up visits were associated with higher overall pill counts while low compliance during screening was associated with lower counts during follow-up. Participants with an overall mean pill count < 80% had more adverse events compared to those with a higher count. Side effects were reported as the reason for missing pills significantly more often in the active versus placebo niacin group. CONCLUSIONS: Individuals with peripheral arterial disease were able to comply with the complex drug regimen. The ability of this drug combination to reduce cardiovascular events and improve quality of life warrants study.

Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT) pilot study.

The primary objectives of the pilot study were to: (1) evaluate the feasibility of recruiting patients with peripheral arterial disease (PAD); (2) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment, low-density lipoprotein (LDL)-lowering therapy, antioxidant therapy, antithrombotic therapy, and their combinations; and (3) assess adherence to a complex multiple drug regimen. Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers, maintenance of therapy masking (in particular with niacin), and measurement of the intervention's impact on functional status and on quality of life. To date, no secondary prevention trial has been conducted specifically among patients with PAD. Intermittent claudication affects about 0.5% to 1.0% of persons aged >35 years. There is a striking increase in incidence of PAD with age, particularly among those aged >50 years in both sexes, although men are twice as likely as women to develop PAD. The Arterial Disease Multiple Intervention Trial was a double-blind randomized pilot trial of 468 participants with documented PAD. A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions. The pilot incorporated several major novel design features: first, the use of a simple noninvasive method (measurement of ankle brachial index) to identify a population with either symptomatic or asymptomatic PAD; and second, a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group. Two other arms, the antioxidant arm (consisting of beta-carotene and vitamins E and C) and the antithrombotic arm (using warfarin) were also added. Adherence to therapy was measured by pill count, and success in treatment was measured by the proportion of values in target range for HDL, LDL, and the international normalized ratio.

Collagen N-telopeptide excretion in men: the effects of age and intrasubject variability.

Biochemical markers of bone resorption are useful for evaluating metabolic bone diseases. A three-center study was performed in 253 men, 21-86 yr of age, to determine the normal range of urinary N-telopeptide of type I collagen (NTX/creatinine) in a nonfasting, second void, morning specimen, to define the biological variability and to examine the relationship between NTX/creatinine and age. Men with disorders or taking medications known to alter bone turnover, or with a serum creatinine level greater than 2 mg/dL were excluded. Results are expressed as nanomoles of bone collagen equivalents (BCE) per mmol creatinine. In a subset of individuals over age 30 yr, additional second void morning urine specimens were obtained at 2, 3, and 4 days (short term study) and at 2, 3, and 4 months (long term study) after the first specimen. After collection, samples were shipped to one laboratory for analysis. Multiple samples from the same subject were analyzed in separate assays. It was found that urinary NTX/ creatinine was significantly higher in 45 men, aged 21-30 yr, than in 206 men, aged 31-86 yr (48 +/- 22 vs. 33 +/- 15 nmol/L BCE/mmol/L creatinine; P < 0.00001). Values did not otherwise change with age. The range of values in men aged 21-30 yr was 4-92 nmol/L BCE/mmol/L creatinine. The range for men over age 30 yr was 3- 63 nmol/L BCE/mmol/L creatinine, essentially the same as that previously reported for premenopausal women. The coefficient of variation was determined in each individual for the short term (n = 36) and long term studies (n = 35) and averaged 18% and 19%, respectively. There was no correlation between short term and long term coefficient of variations. In summary, urinary NTX/creatinine is higher in men aged 21-30 yr than in men over age 30 yr and may reflect continued skeletal maturation. Intrasubject variability of urinary NTX/creatinine in short term and long term studies has been defined for clinical purposes.

Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?

One hundred three patients with leukemia, aplastic anemia, or myelodysplastic syndrome were treated by marrow transplantation from genotypically HLA-identical siblings (n = 92) or HLA haploidentical family members differing for one HLA antigen on the nonshared haplotype (n = 11). To prevent graft-vs.-host disease (GVHD), they were administered postgrafting immunosuppression with a short course of intermittent methotrexate with daily cyclosporine for no more than 11 days. Customarily, we have given cyclosporine for 180 days after transplant. In the current study, we asked whether cyclosporine could be stopped earlier without affecting the risk of chronic GVHD. By day 60, patients who never had acute GVHD, or whose acute GVHD had resolved, were randomized to have cyclosporine stopped (n = 52) or continued for the usual 180 days (n = 51). Results were analyzed with a median follow-up of 9.3 years after transplant, and showed that patients in whom cyclosporine was discontinued on day 60 had a significantly more rapid onset (p = 0.001), but not a significantly higher overall incidence of chronic GVHD than those in whom the drug was stopped on day 180 (43 vs. 54%; p = 0.26). Transplant-related mortality was comparable among patients without preceding acute GVHD, regardless of when cyclosporine was discontinued (11% for both study arms). However, transplant-related mortality appeared to increase among patients with preceding acute GVHD in whom cyclosporine was stopped by day 60 (38 vs. 17%). Results suggest that cyclosporine can safely be discontinued early in patients who never had evidence of acute GVHD, while those with preceding acute GVHD would benefit from a longer course of the drug. Because of the relatively small sample sizes, these results would best be treated as promising preliminary findings that should be confirmed in larger randomized studies.

Simulation as a design tool for phase I/II clinical trials: an example from bone marrow transplantation.

We discuss the design and analysis of a proposed phase I/II clinical trial in bone marrow transplantation whereby dose modifications that decrease the risk of one complication increase the risk of another. Trials of this type are carried out to determine whether a dose can be found that balances the risks of each complication. Three different scenarios describing potential relationships between each risk and the treatment dose are postulated. The scenarios encompass both favorable situations in which several acceptable doses exist and unfavorable situations in which no acceptable dose exists. The operating characteristics of three sequentially developed trial designs were examined by simulation under each dose-response scenario. The first design was derived from seemingly reasonable rules, but simulations showed that performance fell far short of what was desired, thus motivating modifications. Subsequent designs showed improved performance characteristics compared to the original design. Without close examination of the operating characteristics, the original design would have been implemented, leading to high risk of an erroneous conclusion.

Clinical manifestations of genital infection due to Chlamydia trachomatis in women: differences related to serovar.

The relationship between the infecting Chlamydia trachomatis serovar and the clinical manifestations of genital tract infection was evaluated in a study of 155 women attending a sexually transmitted diseases clinic; 99 women had lower genital tract infection and 56 had Chlamydia-associated pelvic inflammatory disease (PID). In the group with lower genital tract infection, women with serovar F differed from those with serovars of class B or C in that they exhibited fewer signs of cervical infection, including easily induced bleeding (P = .04), edema of the zone of cervical ectopy (P = .06), and colposcopic evidence of mucopurulent endocervical discharge (P = .007). Serovar F also produced fewer infections with inclusion counts of > or = 1,000 and fewer rectal infections (P = .04). There was no apparent association of any specific serovar with PID. Thus, in this population, serovar F was associated with fewer objective clinical manifestations of mucopurulent endocervical discharge, and the distribution of chlamydial serovars found in PID reflected that found in lower genital tract infection.

'Resistance' to unrelated, DLA-nonidentical canine marrow grafts is unrestricted by the major histocompatibility complex.

Dogs undergoing rejection of unrelated, dog leukocyte antigen (DLA)-nonidentical marrow grafts show an increase in mononuclear cell counts in the peripheral blood at 1 week after transplant. Cells are of host origin and express phenotypic and morphologic characteristics of large granular lymphocytes (LGLs). LGLs from rejecting dogs suppress in vitro growth of donor marrow colony-forming units-granulocyte/macrophage (CFU-GM) and have natural killer (NK) cell activity. The current study tested whether the marrow-suppressive activity of LGLs obtained at the time of marrow graft rejection was major histocompatibility complex (MHC)-restricted. Five dogs were in the process of rejecting their DLA-nonidentical unrelated marrow grafts after conditioning with 9.2 Gy total-body irradiation (TBI). At the time of rejection, peripheral blood mononuclear cells (PBMC) were harvested. PBMC were co-cultured with marrow obtained from the original marrow transplant donor and from other unrelated dogs that were either DLA-identical or -nonidentical with the marrow donor. A statistically significant reduction of marrow donor CFU-GM was seen when compared to results with autologous effector PBMC from the marrow donor. The number of colonies with recipient effector PBMC ranged from 8 to 75% (median 29%). No suppression was seen with PBMC effectors from unrelated DLA-identical or DLA-nonidentical dogs. Similarly, significant reductions in the number of CFU-GM compared to autologous controls were seen with effector PBMC from marrow recipients and marrow target cells, both from unrelated dogs that were phenotypically DLA-identical or -nonidentical with the marrow donor. The number of colonies ranged from 6 to 68% (median 29%) and 1 to 102% (median 20%), respectively. NK activity was present at low levels in all recipients, while specific alloantigen-primed cytotoxic T cell killing by cells obtained from the five recipients yielded cytolysis of donor PBMC in only one case, suggesting that the marrow-suppressive activity was NK cell-mediated. In conclusion, PBMC from canine marrow transplant recipients undergoing rejection of DLA-nonidentical marrow grafts suppress in vitro CFU-GM growth of marrow donor cells, and this suppression is not MHC-restricted.

FK-506 and methotrexate prevent graft-versus-host disease in dogs given 9.2 Gy total body irradiation and marrow grafts from unrelated dog leukocyte antigen-nonidentical donors.

FK-506 was evaluated either alone or combined with methotrexate (MTX) for prevention of graft-versus-host disease (GVHD) in dogs given 9.2 Gy total body irradiation and dog leukocyte antigen-nonidentical unrelated marrow grafts. Studies with marrow autografts showed gut toxicity and weight loss to be major side effects of FK-506. There was no hematopoietic toxicity with FK-506. In an initial allograft study, 5 dogs were given FK-506 intramuscularly at 0.3 mg/kg/day from days 0 to 8 and then orally at 0.5 mg/kg/day. All 5 died, 3 with intussusception most likely due to FK-506 toxicity, 1 with graft failure, and 1 with GVHD. Subsequently, the FK-506 dose was reduced and these drug schedules were used: FK-506 days 0-8 at 0.15 mg/kg/day i.m. and then orally at 0.5 mg/kg/day until day 90, with or without MTX intravenously at 0.4 mg/kg days 1, 3, 6, and 11. Twenty allografts were done, 10 with FK-506 alone, and 10 with MTX/FK-506. Results were compared with those in concurrent and historical controls given either no immunosuppression (n = 64), MTX (n = 114), CsA (n = 15), or MTX/CsA (n = 17). Five of 20 current dogs died with intussusception, too early to be evaluated for GVHD. The 10 dogs given FK-506 alone survived significantly better than those not given immunosuppression but not differently from those given short-term MTX or CsA alone. Three died from toxicity, 2 with graft failure, and 4 with GVHD. Only 1 dog became a long-term survivor, and this dog inadvertently received a single dose of MTX on day 7. Two of 10 dogs given MTX/FK-506 died from toxicity, 1 died with graft failure, 2 died with GVHD, and 5 became long-term survivors, a result that is significantly better than seen with either drug alone and similar to that seen with MTX/CsA. Four of the 5 survivors had no clinical GVHD. FK-506 blood levels were 15-35 ng/ml between days 8 and 15, when gut toxicity was most severe. Thereafter, levels were approximately 5 ng/ml. In conclusion, FK-506 prolonged survival of recipients of dog leukocyte antigen-nonidentical unrelated marrow grafts. When FK-506 was combined with MTX, graft-host tolerance was induced in 50% of dogs, even though FK-506 was stopped on day 90.

Ganciclovir sensitivity of cytomegalovirus at diagnosis and during treatment of cytomegalovirus pneumonia in marrow transplant recipients.

Cytomegalovirus (CMV) often persists in the lungs of marrow transplant patients with CMV pneumonia, despite ganciclovir (GCV) treatment. To determine whether GCV resistance contributes to viral persistence, the susceptibilities of CMV isolates from diagnostic bronchoalveolar lavage samples and CMV isolates obtained during treatment or from autopsy lung tissue from 12 patients were compared by DNA hybridization. Resistance (50% effective dose, > 12 microM) was detected in an isolate from only one patient who had also received several courses of GCV. GCV resistance did not explain the persistence of CMV in the lung.

Summarizing data on survival, relapse, and chronic graft-versus-host disease after bone marrow transplantation: motivation for and description of new methods.

Kaplan-Meier curves are frequently used to summarize survival, relapse, and chronic graft-versus-host disease (GVHD) data in the bone marrow transplant setting. Some fundamental problems with the use of Kaplan-Meier curves for the summary of relapse and GVHD are described. Alternatively, the use of simple probability and conditional probability curves for summarizing relapse incidence and transplant-related mortality is illustrated with previously published data from a randomized clinical trial. Prevalence curves provide an appropriate alternative for the summary of a transient condition such as chronic GVHD. When combined with Kaplan-Meier curves for survival and/or relapse-free survival, these methods provide a more accurate and comprehensive summary of the various marrow transplant outcomes. These methods of display are also applicable to other settings where more than one type of treatment failure can occur and where follow-up time may be variable.

Association of genital infection with specific Chlamydia trachomatis serovars and race.

Black race is an important risk marker for Chlamydia trachomatis genital infection. To define whether C. trachomatis serovars differ by ethnic distribution, a panel of monoclonal antibodies was used to serotype 934 urethral and 581 cervical isolates from patients attending a sexually transmitted diseases clinic over 2 years. The overall serovar distribution in cervical and urethral infections was comparable, with B class serovars predominating. Significantly higher inclusion counts were observed both in younger women and in nonblacks regardless of serovar. Serovar D was less frequent among blacks at the urethral site (P = .001), while serovar Ia was more frequent in blacks at both sites (urethral, P < .001; cervical, P = .02). These associations remained significant after adjusting for age and number of inclusion-forming units by multivariate analysis. Thus, specific serovars may be associated with particular racial groups; either behavioral or biologic factors could explain these findings.