FGF receptor genes and breast cancer susceptibility: results from the Breast Cancer Association Consortium.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Preliminary validity testing of the eHealth Literacy Questionnaire (eHLQ): a Confirmatory Factor Analysis (CFA) in Norwegian hospitalized patients.

AIMS: To perform the first psychometric analysis of the Norwegian version of the eHLQ using confirmative factor analysis (CFA) procedures in a population of patients admitted to hospital using a cross-sectional design. The eHLQ consists of 35 items capturing the 7-dimensional eHealth Literacy Framework (eHLF) which describes users' attributes, user's interaction with technologies and user's experience with digital health systems. METHODS: The 7 independent scales of the eHLQ was translated from Danish and culturally adapted into the Norwegian language following a standardised protocol. Assessment of construct validity of the eHLQ was undertaken using data from a cross-sectional survey of 260 patients hospitalized at a Norwegian University Hospital in the Oslo area during a two-week period in June 2021. The analysis included using correlation analysis (Pearsons R), internal consistency (Cronbach's alpha) and confirmatory factor analysis (CFA). RESULTS: All factor loadings were high to acceptable (i.e. > 0.6), except for five items which had somewhat lower loadings. Regarding internal consistency, alpha ranged from 0.73 to 0.90. For optimal CFA fit for the different scale models, correlated residuals were required for five of the seven scales. Overall our analysis shows an intermediate fit of the orginal construct. Scale intercorrelations were all below 0.8, indicating an overall acceptable discriminant validity between the 7 dimensions. CONCLUSIONS: The results from the CFA analysis indicate that for almost all 7 eHLQ scales, an acceptable model fit was achieved. The 260 hospitalized patients included in this study represented a variety of diagnoses, recruited from a geographically limited area. Further studies on psychometric properties of the Norwegian version of eHLQ in larger samples, diverse settings and by using more comprehensive approaches are warranted.

Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

scRNA-seq assessment of the human lung, spleen, and esophagus tissue stability after cold preservation.

BACKGROUND: The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design. RESULTS: This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific. CONCLUSIONS: In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.

Benzene and its phenolic metabolites produce oxidative DNA damage in HL60 cells in vitro and in the bone marrow in vivo.

Benzene, an important industrial chemical, is myelotoxic and leukemogenic in humans. It is metabolized by cytochrome P450 2E1 to various phenolic metabolites which accumulate in the bone marrow. Bone marrow contains high levels of myeloperoxidase which can catalyze the further metabolism of the phenolic metabolites to reactive free radical species. Redox cycling of these free radical species produces active oxygen. This active oxygen may damage cellular DNA (known as oxidative DNA damage) and induce genotoxic effects. Here we report the induction of oxidative DNA damage by benzene and its phenolic metabolites in HL60 cells in vitro and in the bone marrow of C57BL/6 x C3H F1 mice in vivo utilizing 8-hydroxy-2'-deoxyguanosine as a marker. HL60 cells (a human leukemia cell line) contain high levels of myeloperoxidase and were used as an in vitro model system. Exposure of these cells to phenol, hydroquinone, and 1,2,4-benzenetriol resulted in an increased level of oxidative DNA damage. An increase in oxidative DNA damage was also observed in the mouse bone marrow in vivo 1 h after benzene administration. A dose of 200 mg/kg benzene produced a 5-fold increase in the 8-hydroxydeoxyguanosine level. Combinations of phenol, catechol, and hydroquinone also resulted in significant increases in steady state levels of oxidative DNA damage in the mouse bone marrow but were not effective when administered individually. Administration of 1,2,4-benzenetriol alone did, however, result in a significant increase in oxidative DNA damage. This represents the first direct demonstration of active oxygen production by benzene and its phenolic metabolites in vivo. The conversion of benzene to phenolic metabolites and the subsequent production of oxidative DNA damage may therefore play a role in the benzene-induced genotoxicity, myelotoxicity, and leukemia.

Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone.

Benzene is a ubiquitous occupational hematotoxin and leukemogen, but people vary in their response to this toxic agent. To evaluate the impact of interindividual variation in enzymes that activate (i.e., CYP2E1) and detoxify (i.e., NQO1) benzene and its metabolites, we carried out a case-control study in Shanghai, China, of occupational benzene poisoning (BP; i.e., hematotoxicity), which we show is itself strongly associated with subsequent development of acute nonlymphocytic leukemia and the related myelodysplastic syndromes (relative risk, 70.6; 95% confidence interval, 11.4-439.3). CYP2E1 and NQO1 genotypes were determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50 controls. Subjects with both a rapid fe(6-OH). and two copies of the NQO1 609C-->T mutation had a 7.6-fold (95% confidence interval, 1.8-31.2) increased risk of BP compared to subjects with a slow fe(6-OH) who carried one or two wild-type NQO1 alleles. In contrast, the CYP2E1 PstI/RsaI polymorphism did not influence BP risk. This is the first report that provides evidence of human susceptibility to benzene-related disease. Further evaluation of susceptibility for hematotoxicity and hematological malignancy among workers with a history of occupational exposure to benzene is warranted.

Decision analysis in clinical cardiology: when is coronary angiography required in aortic stenosis?

Decision analysis offers a reproducible, explicit approach to complex clinical decisions. It consists of developing a model, typically a decision tree, that separates choices from chances and that specifies and assigns relative values to outcomes. Sensitivity analysis allows exploration of alternative assumptions. Cost-effectiveness analysis shows the relation between dollars spent and improved health outcomes achieved. In a tutorial format, this approach is applied to the decision whether to perform coronary angiography in a patient who requires aortic valve replacement for critical aortic stenosis.

Human immunodeficiency virus infection in health care workers. A method for estimating individual occupational risk.

Physicians and other health care workers are concerned about their occupational risk of acquiring human immunodeficiency virus infection. We have developed an approach that can help health care workers estimate their cumulative risk of infection with human immunodeficiency virus. Illustrations are used to develop a score that reflects an individual's occupational exposures and social behavior. This score is then translated into the probability that the worker is infected.

Effects of complement depletion on the pharmacokinetics and gene delivery mediated by cationic lipid-DNA complexes.

We show that lipoplexes activate complement in human serum in vitro and deplete complement when administered intravenously (i.v.) to mice. This raised the possibility that complement proteins might alter gene expression mediated by lipoplex in animals. To investigate this phenomenon, complement levels were depleted to less than 5% in ICR mice by intraperitoneal (i.p.) injection of cobra venom factor and anti-C3 antibodies. The pharmacokinetics and distribution of radio labeled DOTAP-cholesterol (1.0:0.9 molar ratio)-DNA (5:1 positive charge ratio) complexes containing 131I-labeled p-hydroxybenzamidine phosphatidylethanolamine and 125I-labeled DNA were measured in mice after i.v. administration. Greater than 75% of the injected lipoplex appeared in the lungs 5 min following injection. The lipid and DNA were eliminated from the lungs at a constant ratio. Distribution in various organs was not affected by complement depletion. Expression of luciferase was highest in the lungs and showed a dose-dependent increase as the amount of DNA injected increased from 3 to 60 microg. Reporter gene expression was not affected by complement depletion. In addition, complement depletion had no effect on either the distribution or gene expression in the heart, spleen, or liver. We conclude that cationic lipid-DNA complexes interact with serum complement proteins upon i.v. injection in mice, but this interaction does not influence the lipofection efficiency or systemic distribution of the lipoplex.

Ablative radioactive iodine therapy for apparently localized thyroid carcinoma. A decision analytic perspective.

Adjuvant therapy with ablative radioiodine after surgical resection of apparently localized thyroid carcinoma remains controversial because of the favorable prognosis of thyroid carcinoma and the risk of leukemia from the radioiodine. No controlled trials have been performed to examine this issue. We constructed a decision analytic model to examine whether patients with apparently localized thyroid carcinoma should receive radioiodine. Our analysis suggests that radioiodine modestly improves life expectancy by 2 to 15 months, depending on the patient's age and sex. This model predicts that the benefit of a reduction in the likelihood of recurrence outweighs the risk of leukemia from radioiodine.

Correlation of pediatric echocardiographic Doppler and catheter-derived valvar aortic stenosis gradients and the influence of aortic regurgitation.

This report suggests that in the absence of aortic regurgitation, Doppler peak and mean gradients are useful predictors of catheter peak-to-peak aortic stenosis gradients >50 mm Hg; however, in the presence of aortic regurgitation, the predictive value diminishes dramatically, but improves when electrographic data are incorporated. We present potentially useful equations to help predict the need for interventional catheterization for valvar aortic stenosis.

Formal literature review of quality-of-life instruments used in end-stage renal disease.

Although quality-of-life assessment is an important complement to conventional clinical evaluation, there are limited opportunities for researchers in end-stage renal disease (ESRD) to examine evidence for a range of quality-of-life measures. To better understand how quality of life has been conceptualized, measured, and evaluated for ESRD, we conducted a structured literature review. Eligible articles were identified from a MEDLINE search, expert input, and review of references from eligible articles. A standardized instrument was created for article review and included type of measure, instrument development process, study sample characteristics, quality-of-life domains, and reliability and validity testing. From 436 citations, 78 articles were eligible for final review, and of those, 47 articles contained evidence of reliability or validity testing. Within this set, there were 113 uses of 53 different instruments: 82% were generic and 18% were disease specific. Only 32% defined quality of life. The most frequently assessed domains were depression (41%), social functioning (32%), positive affect (30%), and role functioning (27%). Testing was completed for test-retest reliability (20%), interrater reliability (13%), internal consistency (22%), content validity (24%), construct validity (41%), criterion validity (55%), and responsiveness (59%). Few articles measuring quality of life in ESRD defined quality-of-life domains or adequately described instrument development and testing. Generic measures, such as the Sickness Impact Profile, and disease-specific measures, such as the Kidney Disease Questionnaire, had been tested more thoroughly than others. Standardized reporting and more rigorous testing could help researchers make informed choices about instruments that would best serve their own and their patients' needs.

Developing a health-related quality-of-life measure for end-stage renal disease: The CHOICE Health Experience Questionnaire.

The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease ([ESRD] CHOICE) Study was designed to evaluate the effectiveness of alternative dialysis prescriptions. As part of CHOICE, we developed an instrument for measuring health-related quality of life (HRQOL) for patients with ESRD that would complement the Medical Outcomes Study 36-Item Short-Form Survey (SF-36) and be sensitive to differences in dialysis modality (hemodialysis [HD] and peritoneal dialysis [PD]) and dialysis dose. The selection of HRQOL domains to be included was based on: (1) a structured literature review of 47 articles describing 53 different instruments; (2) content analysis of five focus groups with HD and PD patients, nephrologists, and other providers; (3) a survey of 110 dialysis providers about features of different modalities that affect patient HRQOL; and (4) a semistructured survey of 25 patients with ESRD on the effects of dialysis on functioning and HRQOL. To help prioritize domains and items identified by these methods, a representative sample of 136 dialysis patients rated each item for frequency and bother. A panel of nephrologists provided advice about the salience of items to modality or dose. Items and scales were selected with a preference for existing measures tested in patients with ESRD and were tested for reliability and validity. The first four steps yielded 22 HRQOL domains that included 96 items: 8 generic domains in the SF-36 (health perceptions, physical, social, physical and emotional role function, pain, mental health, and energy); 8 additional generic domains (cognitive functioning, sexual functioning, sleep, work, recreation, travel, finances, and general quality of life); and 6 ESRD-specific domains (diet, freedom, time, body image, dialysis access [catheters and/or vascular], and symptoms). New items were developed or adapted to assess ESRD-specific domains. Scales for these items showed adequate internal consistency (Cronbach's alpha > 0.70, except for time [alpha = 0.57] and quality of life [alpha = 0.68]), as well as convergent and discriminant construct validity in a sample of 928 patients. The final questionnaire included 21 domains (time was deleted) and 83 items. We have designed a patient-centered instrument, the CHOICE Health Experience Questionnaire, that addresses domains that may be sensitive to differences in dialysis modality and dose and shows evidence for reliability and validity as a measure of HRQOL in ESRD.

An epidemiologic study of early biologic effects of benzene in Chinese workers.

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans.

Use of focus groups to identify concerns about dialysis. Choice Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) may have quality-of-life (QOL) concerns that are not fully appreciated by their providers. The authors conducted focus groups with dialysis patients and dialysis professionals to determine whether this qualitative method would reveal differences between patients' and providers' views about: 1) domains of QOL that are affected by ESRD and dialysis; and 2) aspects of dialysis that affect QOL. METHODS: Separate focus group discussions were held with: 8 adult hemodialysis patients (mean age 50 years; 3 women; mean duration of dialysis 8.5 years), 5 adult peritoneal dialysis patients (mean age 54 years; 3 women; mean duration of dialysis 4.6 years), 8 nephrologists (mean of 12 years of dialysis practice), and 9 other health professionals involved in dialysis care (3 nurses, 2 dietitians, 2 social workers, and 2 technicians; mean of 10 years experience in dialysis care). Discussions were audiotaped, transcribed verbatim, and reviewed independently by three investigators to identify and categorize distinct thoughts. RESULTS: 1,271 distinct thoughts were identified and grouped into 20 related categories, which included ten QOL domains and ten aspects of dialysis that affect QOL. Compared with the professionals, the patients identified one additional relevant QOL domain (10 vs 9), and one additional aspect of dialysis that affects QOL (10 vs 9), and expressed more thoughts per domain (p < 0.05), although the contents of their comments were frequently similar. Among QOL domains, the numbers of related thoughts identified by patients and professionals, respectively, were: freedom/control (60, 89); social relationships (36, 11); anxiety (37, 4); role function (24, 10); energy (12, 10); body image (16, 4); sex (11, 21); mental attitude (21, 0); sleep (15, 1), and cognitive function (13, 7). Among aspects of dialysis that affect QOL, the numbers of thoughts identified by patients and professionals were: general dialysis issues (159, 105); relationships with staff (62, 110); patient education (63, 68); diet (44, 40); scheduling (57, 3); vascular or peritoneal access issues (31, 17), adaptation to dialysis (16, 14); dialysis dose (18, 8); symptoms (25, 0), and self-care (5, 24). CONCLUSIONS: Although health professionals have a good understanding of patient concerns about the effects of ESRD and dialysis, the focus group discussions revealed a breadth and depth of QOL concerns that they may not fully appreciate.

Sonographic assessment of fetal cardiac arrhythmias.

The fetus with an arrhythmia may be at high risk both from the arrhythmia itself and from the condition that provoked it. Incorrect diagnosis and inappropriate or delayed treatment may further compound the hazard. Although echocardiography can specifically identify the arrhythmia, this technique requires very skilled and careful examination by a physician who fully understands how to differentiate optimally between similar-appearing but mechanistically different arrhythmias. Congenital heart disease may also be present and must be evaluated specifically. This report describes ultrasound recording techniques used to diagnose arrhythmias and includes a discussion of M-mode echocardiography, two-dimensional imaging, pulsed Doppler, and color-flow Doppler. It also differentiates specific arrhythmias--premature atrial contractions, ventricular tachycardia, atrial flutter, complete heart block, and supraventricular tachycardia--and presents the optimal diagnostic tools for each.

Efficacy and safety of selenium-vitamin E injections in newborn pigs to prevent subclinical deficiency in growing swine.

Seventy-eight newborn pigs were allotted to 4 treatment groups: 22 pigs in group A were given no selenium-vitamin E (Se-E), 22 pigs in group B were given small doses of Se-E, 22 pigs in group C were given medium doses of Se-E, and 12 pigs in group D were given large doses of Se-E. Pigs were intramuscularly injected before 7 days of age and at weaning (40 days of age), respectively, as follows: group A--1 ml of physiologic saline solution/pig each time, group B--0.25 mg of Se/pig and later 0.06 mg of Se/kg of body weight, group C--1.0 mg of Se/pig and later 0.24 mg of Se/kg, and group D--1.5 mg of Se/pig and later 0.72 mg of Se/kg. Selenium was supplied as sodium selenite in commercially available Se-E injectable compounds. From 2 weeks of age to weaning, the pigs were fed a corn-torula yeast creep feed containing Se at the concentration of 0.03 ppm, and from weaning to slaughter, a corn-soybean meal ration was fed containing Se at the concentration of 0.07 ppm and alpha-tocopherol at the concentration of 15.7 mg/kg. Subclinical Se-E deficiency developed in control pigs of group A and was characterized by subtle muscular stiffness, significant increases in plasma activities of glutamic oxalacetic transaminase (GOT) and creatine phosphokinase (CPK), and typical residual lesions in heart and skeletal muscle, but not in liver, at slaughter at 165 days of age. Pigs injected with Se-E did not develop these evidences of subclinical deficiency. Pigs in group D were stunted for several weeks after the 2nd Se-E injection, and plasma GOT and CPK activities were significantly increased at 3 weeks after injection. Growth rates were otherwise similar between groups. Significant difference in Se content of liver, muscle, serum, and hair was not seen between pigs in the 4 groups at 120 and 165 days of age. A test period of physical exertion and heat stress resulted in significant increase of plasma GOT and CPK activities in 4 of 8 pigs at 110 days of age.

Epizootic of pseudorabies among ten swine herds.

An epizootic of pseudorabies in 10 swine herds located near Greensburg in Decatur County, Indiana was investigated. Records of Decatur County swine herds previously quarantined because of pseudorabies were obtained. For the 1988 epizootic, clinical findings were considered, location of each of the 10 swine herds in relation to the other herds was determined, and potential fomites were considered. Meteorologic data prior to, during, and after the epizootic were obtained, correlated, and analyzed. A source-receptor model, based on wind direction and speed data, was used to determine whether weather conditions in the Greensburg area enhanced the potential for aerosol spread of pseudorabies virus between herds. On the basis of lack of other modes of spread of pseudorabies and on meteorologic and source-receptor data, aerosol transmission of pseudorabies virus between the 10 herds was probable.

Testicular testosterone: estradiol ratio in domestic cats and its relationship to spermatogenesis and epididymal sperm morphology.

The phenomenon of teratozoospermia in felids is not fully understood. In this study, we investigated the testicular androgen:estrogen balance in domestic cats and correlated these data with epididymal sperm morphology and the degree of spermatogenic activity. During spring and summer, testes and blood samples were obtained from 37 mixed-breed domestic cats (12 to 48 mo). The epididymal sperm were harvested and evaluated for sperm counts, motility, and morphology. Distal cytoplasmic droplets were not considered a defect, and samples were considered normozoospermic if they contained more than 60% normal sperm (N = 25) or teratozoospermic if they contained less than 45% normal sperm (N = 12). The testicular and serum concentrations of testosterone (T) and 17ß-estradiol (E2) were determined with an enzyme immunoassay. The gonadosomatic index and epididymal sperm numbers and motility did not differ between groups. The percentage of normal sperm was higher in normozoospermic (74.3 ± 2.0, mean ± SEM) than in teratozoospermic samples (43.1 ± 1.4). The most prevalent sperm defects in the teratozoospermic group were abnormal acrosomes (9.7 ± 2.0) and bent midpieces (12.2 ± 2.0) or tails (24.0 ± 2.7) with cytoplasmic droplets. Histomorphometric data were similar between groups, although there was a lower Leydig cell nuclear volume in teratozoospermic samples. Normozoospermic samples contained a higher percentage of haploid cells and had a higher index of total spermatogenic transformation than teratozoospermic samples. Serum concentrations of T (0.5 ± 0.1 vs. 0.8 ± 0.4 ng/mL) and E2 (9.5 ± 1.2 vs. 11.4 ± 2.3 pg/mL) and testicular T concentrations (471.6 ± 65.3 vs. 313.4 ± 57.6 ng/g) were similar between groups. However, compared with normozoospermic samples, teratozoospermic samples had higher testicular E2 concentrations (8.5 ± 3.6 vs. 5.4 ± 0.5 ng/g) and a lower T:E2 ratio (31.8 ± 4.1 vs. 87.2 ± 11.6). There were significant correlations between testicular E2 values and percentages of normal sperm (r = -0.55) as well as those with primary sperm defects (r = 0.58) or abnormal acrosomes (r = 0.64). The T:E2 ratio was also correlated with meiotic index (r = 0.45) and percentage of normal sperm (r = 0.58). In conclusion, a high testicular E2 concentration and a reduced T:E2 ratio were significantly associated with higher ratios of abnormal sperm types, suggesting that the balance between androgens and estrogens is an important endocrine component in the genesis of teratozoospermia in felids.