Eligibility for sacubitril/valsartan in heart failure across the ejection fraction spectrum: real-world data from the Swedish Heart Failure Registry.

BACKGROUND: Randomized controlled trials (RCT) generalizability may be limited due to strict patient selection. OBJECTIVE: In a real-world heart failure (HF) population, we assessed eligibility for sacubitril/valsartan based on PARADIGM-HF (sacubitril/valsartan effective)/PARAGON-HF [sacubitril/valsartan effective in mildly reduced ejection fraction (EF)]. METHODS: Outpatients from the Swedish HF Registry (SwedeHF) were analysed. In SwedeHF, EF is recorded as <30, 30-39, 40-49 and ≥50%. In PARAGON-HF, sacubitril/valsartan was effective with EF ≤ 57% (i.e. median). We defined reduced EF/PARADIGM-HF as EF < 40%, mildly reduced EF/PARAGON-HF ≤ median as EF 40-49%, and normal EF/PARAGON-HF > median as EF ≥ 50%. We assessed 2 scenarios: (i) criteria likely to influence treatment decisions (pragmatic scenario); (ii) all criteria (literal scenario). RESULTS: Of 37 790 outpatients, 57% had EF < 40%, 24% EF 40-49% and 19% EF ≥ 50%. In the pragmatic scenario, 63% were eligible in EF < 50% (67% for EF < 40% and 52% for 40-49%) and 52% in EF ≥ 40% (52% for EF ≥ 50%). For the literal scenario, 32% were eligible in EF < 50% (38% of EF < 40%, 20% of EF 40-49%) and 22% in EF ≥ 40% (25% for EF ≥ 50%). Eligible vs. noneligible patients had more severe HF, more comorbidities and overall worse outcomes. CONCLUSION: In a real-world HF outpatient cohort, 81% of patients had EF < 50%, with 63% eligible for sacubitril/valsartan based on pragmatic criteria and 32% eligible based on literal trial criteria. Similar eligibility was observed for EF 40-49% and ≥50%, suggesting that our estimates for EF < 50% may be reproduced whether or not a higher cut-off for EF is considered.

Construction and validation of the Lebanese Osteoporosis Knowledge Scale among a representative sample of Lebanese women.

Our study aimed at constructing and validating the Lebanese Osteoporosis Knowledge Scale adapted for use among Lebanese women and to assess factors associated with the poorest knowledge of osteoporosis definition, risk factors, and preventive measures. This scale showed adequate psychometric properties; higher knowledge scores were reached in women who already heard about the disease and had a formal education. As a result, the LOKS-19 can be used to measure knowledge of osteoporosis and help assess osteoporosis-related interventions. INTRODUCTION: The primary objective of this study was to describe the construction of the Lebanese Osteoporosis Knowledge Scale (LOKS) and assess its psychometric properties in a representative sample of Lebanese women aged 40 years and above. Secondary objectives were to explore factors associated with this knowledge score. METHODS: A cross-sectional study carried out between March and June 2018, enrolled 560 women over the age of 40 years living in the community. This proportionate sample was randomly selected from all Lebanese governorates to cover the entire Lebanese area. A survey was developed and adapted to the Lebanese population based on preexisting scales. Personal interviews were conducted to collect data. RESULTS: The items of the LOKS were distributed across seven factors with an Eigenvalue over 1 solution, outlining an overall value of 55.89% of the variance. A high Cronbach's alpha was found for the full scale (0.725). Individuals having a university level of education (beta = 1.62; compared to illiteracy), having heard of osteoporosis (beta = 2.62), taking supplements of calcium and vitamin D compared to none (beta = 0.77), and having had Crohn's disease (beta = 1.71) had significantly higher knowledge scores of osteoporosis; oppositely, having diabetes (beta = - 1.17), currently taking chemotherapy (beta = - 2.25), and ever having had a fracture (beta = - 0.74) were significantly correlated with lower awareness of osteoporosis. CONCLUSIONS: Our findings suggest that the LOKS-19 can be used to measure knowledge of osteoporosis and help assess osteoporosis-related interventions. A better knowledge seems to be associated with more preventive measures and less risk of fracture.

Acromegaly in the setting of Tatton-Brown-Rahman Syndrome.

PURPOSE: Tatton-Brown-Rahman syndrome (TBRS) is a newly defined genetic entity characterized by overgrowth and intellectual disability, resulting from germline mutations in the gene encoding DNA methyltransferase 3 alpha (DNMT3A). Affected individuals with benign and malignant tumors have been reported; to our knowledge pituitary adenomas (and other tumors identified in our patient) have not yet been described in this syndrome. CASE: We report the case of a 34-year-old woman with TBRS who developed a GH-secreting pituitary macroadenoma and other benign tumors and cystic lesions involving diverse organ systems. Whole-exome sequencing revealed a heterozygous, likely pathogenic variant (c.700_709 del10, p. Gly234ArgfsX79) in exon7 of DNMT3A, and a heterozygous variant of uncertain significance (c.25 C>T, p.Arg9Trp) in exon 1 of the gene encoding aryl hydrocarbon receptor-interacting protein (AIP). The patient failed somatostatin analog treatment, and underwent surgery. The tumor retained AIP expression, and analysis of tumor DNA indicated the presence of both AIP alleles, consistent with no loss of heterozygosity. These findings suggest that the AIP variant was not the primary driver of pituitary adenoma development. CONCLUSION: Our case suggests that TBRS might be associated with pituitary adenoma and a broader spectrum of tumors than previously thought, making long-term follow up of these patients crucial to identify tumors early, and to elucidate the clinical spectrum of the disorder for optimization of management.

Osteoporosis awareness and health beliefs among Lebanese women aged 40 years and above.

Our study investigated the characteristics of Lebanese women population groups with the poorest knowledge of osteoporosis definition, risk factors, and preventive measures in order to identify categories that should be targeted in future campaigns and educational programs. Higher knowledge scores were reached in women who already heard about the disease and had a formal education. As a result, osteoporosis awareness campaigns and educational programs are mostly needed in populations with lower educational levels. INTRODUCTION: Our study investigated the characteristics of Lebanese women population groups with the poorest knowledge of osteoporosis definition, risk factors, and preventive measures. METHODS: A cross-sectional study, conducted between March and June 2018, enrolled 560 community dwelling women aged 40 years and above. A questionnaire was used to collect data. A proportionate random sample from all Lebanese Mohafazat was used. Data collection was performed through personal interviews. The median was used as a cutoff point for both the Knowledge and Health Belief scales. RESULTS: The study results showed that 47.3% of participants had a poor knowledge score. Women who received no education, compared to a higher education and have not previously heard about the disease, had lower knowledge scores. In addition, women not taking calcium and vitamin D supplements and not exercising or exercising less than 20 min per day compared to those having these characteristics had lower osteoporosis knowledge levels. A lower knowledge score was associated with less recognized benefits of adequate calcium intake and regular physical activity, more perceived barriers towards their practice, and a less important health motivation. A lower level of education correlated to the same results. CONCLUSION: Lower knowledge scores were reached in women who have never heard of osteoporosis and had a lower level of education. As a result, osteoporosis awareness campaigns and educational programs need to target population categories with lower educational levels.

Left atrial rather than left ventricular impaired mechanics are associated with the pro-fibrotic ST2 marker and outcomes in heart failure with preserved ejection fraction.

AIMS: Left ventricular (LV) mechanics have been extensively investigated in heart failure with preserved ejection fraction (HFpEF) overshadowing for a long time the potential role of left atrium (LA) in that setting. Soluble suppression of tumorigenicity-2 receptor (ST2) is a novel biomarker of pro-fibrotic burden in HF. We hypothesized that due to the thinner LA wall, the fibrotic myocardial changes in HFpEF as indicated by elevated ST2 levels might more readily be reflected by impairments in the LA rather than the LV performance. METHODS AND RESULTS: In 86 patients with HFpEF, enrolled in the Karolinska Rennes (KaRen) biomarker prospective substudy, global LA strain (GL-LS) along with other echocardiographic as well as haemodynamic parameters and ST2 levels were measured. ST2 levels were inversely associated with LA-GS (r = -0.30, P = 0.009), but not with LA size, LV geometry, systolic or diastolic LV function (P > 0.05 for all). Furthermore, symptom severity correlated with ST2 and LA-GS, but not with LV structural or functional indices. Finally, during a median 18-month follow-up, LA-GS independently predicted the composite endpoint of HF hospitalization and all-cause mortality, even after adjustment for potential clinical and cardiac mechanical confounders, including LV global longitudinal strain and filling pressures (odds ratio: 4.15; confidence interval: 1.2-14, P = 0.023). CONCLUSIONS: Reduced LA-GS but not LV functional systolic and diastolic parameters were associated with the pro-fibrotic ST2 marker, HF symptoms and outcome in HFpEF.

Two-photon microscopy with a frequency-doubled fully fusion-spliced fiber laser at 1840 nm.

We introduce a fiber-based laser system providing 130 fs pulses with 3.5 nJ energy at 920 nm at a 43 MHz repetition rate and illustrate the potential of the source for two-photon excited fluorescence microscopy of living mouse brain. The laser source is based on frequency-doubling high-energy solitons generated and frequency-shifted to 1840 nm in large mode area fibers. This simple laser system could unleash the potential of two-photon microscopy techniques in the biology laboratory where green fluorescent proteins with two-photon absorption spectrum peaking around 920 nm are routinely used.

Chronic phalaris toxicity in macropods is widespread and peaks in July in Victoria, Australia.

Phalaris aquatica is pasture species introduced into Australia during early European settlement. Consumption of the plant can cause the neurological condition chronic phalaris toxicity (CPT) in sheep and cattle. In recent years, there has been an increase in reports of CPT in macropods, which has raised concerns regarding its impacts on their welfare. Currently, little is known about the distribution or seasonal patterns of this disease in wildlife, information pivotal in assessing its potential risks. Between 2021 and 2022, we conducted a survey targeting government bodies, veterinary businesses and wildlife organisations to investigate the locations and time of occurrence of CPT in macropods in the state of Victoria, Australia. We received 13 survey responses, 12 verbal reports, a full record of investigated cases from a university veterinary school and cases from a wildlife rescue organisation. Over the period of 11 years, Victoria had 918 cases of CPT recorded in macropods from 36 local government areas, with cases concentrated centrally just north of the state capital of Melbourne and July (midwinter) being the month with the highest case count (n = 220). There was a significant positive correlation between case count and both the abundance of kangaroos (Macropus giganteus and Macropus fuliginosus) (P < 0.01) and the abundance of P. aquatica (P = 0.009), and a significant negative correlation between annual case count and average rainfall of March (P = 0.016) and April (P = 0.02). Understanding these relationships will assist land and wildlife managers in predicting the risk and magnitude of disease outbreaks of CPT each in Victoria.

Sitagliptin improves beta-cell function in patients with acute coronary syndromes and newly diagnosed glucose abnormalities--the BEGAMI study.

BACKGROUND: Newly detected impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM) are common in patients with acute coronary syndrome (ACS; i.e. unstable angina/myocardial infarction) and related to disturbed beta-cell function. The aim of this study is to test the hypothesis that treatment with a dipeptidyl peptidase-4 inhibitor initiated soon after a coronary event improves beta-cell function. METHODS: Acute coronary syndrome ACS patients with IGT or T2DM (n = 71), screened by oral glucose tolerance test (OGTT) 4-23 days (median 6 days) after hospital admission, were randomly assigned to sitagliptin 100 mg (n = 34) or placebo (n = 37) and treated for a duration of 12 weeks. All patients received lifestyle advice but no glucose-lowering agents other than the study drug. The study end-point was beta-cell function assessed using the insulinogenic index (IGI = ΔInsulin30 /ΔGlucose30 ), derived from an OGTT, and acute insulin response to glucose (AIRg) assessed by a frequently sampled intravenous glucose tolerance test. RESULTS: The IGI and AIRg did not differ at baseline between the sitagliptin and placebo groups (69.9 vs. 66.4 pmol mmol(-1) and 1394 vs. 1106 pmol L(-1) min(-1) respectively). After 12 weeks, the IGI was 85.0 in the sitagliptin and 58.1 pmol/mmol in the placebo group (P = 0.013) and AIRg was 1909 and 1043 pmol L(-1) min(-1) (P < 0.0001) in the sitagliptin and placebo groups respectively. Fasting glucose at baseline was 6.1 mmol L(-1) in sitagliptin-treated patients and 6.0 mmol L(-1) in those who received placebo compared with 5.8 and 5.9 mmol L(-1) respectively, after 12 weeks of treatment. Post load glucose metabolism improved in significantly more sitagliptin-treated patients compared with the placebo group (P = 0.003). Sitagliptin was well tolerated. CONCLUSION: Sitagliptin improved beta-cell function and glucose perturbations in patients with ACS and newly diagnosed glucose disturbances.

Relationship between iron deficiency and expression of genes involved in iron metabolism in human myocardium and skeletal muscle.

BACKGROUND: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake. METHODS: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing. RESULTS: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF physiology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin<100 µg/L). Analysing the correlation between various iron parameters, S-Ferritin levels showed the strongest correlation with TfR1 expression. There was no correlation with NT-proBNP levels and no difference in TfR1 expression between different HF phenotypes. CONCLUSIONS: In patients undergoing elective CABG we found an association between ID and increased TfR1 expression in myocardium regardless of LV function, indicating physiologically upregulated TfR1 expression in the presence of ID to restore intracellular iron needs. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT03671122.

Investigation of breed differences in plasma adrenocorticotropic hormone concentrations among healthy horses and ponies.

Plasma adrenocorticotropic hormone (ACTH) concentration is commonly measured to diagnose pituitary pars intermedia dysfunction (PPID). Several intrinsic and extrinsic factors affect ACTH concentrations, including breed. The objective of this study was to prospectively compare plasma ACTH concentrations among different breeds of mature horses and ponies. Three breed groups comprised Thoroughbred horses (n = 127), Shetland ponies (n = 131) and ponies of non-Shetland breeds (n = 141). Enrolled animals did not show any signs of illness, lameness or clinical signs consistent with PPID. Blood samples were collected 6 months apart, around the autumn equinox and spring equinox, and plasma concentrations of ACTH were measured by chemiluminescent immunoassay. Pairwise breed comparisons within each season were performed on log transformed data using the Tukey test. Estimated mean differences in ACTH concentrations were expressed as fold difference with 95 % confidence intervals (CI). Reference intervals for each breed group per season were calculated using non-parametric methods. In autumn, higher ACTH concentrations were found among non-Shetland pony breeds compared with Thoroughbreds (1.55 fold higher; 95 % CI, 1.35-1.77; P < 0.001), and in Shetland ponies compared with Thoroughbreds (2.67 fold higher; 95 % CI, 2.33-3.08; P < 0.001) and non-Shetland pony breeds (1.73 fold higher; 95 % CI, 1.51-1.98; P < 0.001). In spring, no differences were identified among breed groups (all P > 0.05). Reference intervals were similar among breed groups in spring, but upper limits for ACTH concentrations were markedly different between Thoroughbred horses and pony breeds in autumn. These findings emphasise that breed should be accounted for when determining and interpreting reference intervals for ACTH concentrations among healthy horses and ponies in autumn.

A survey of veterinarians' practices, recommendations and perceptions associated with the prevention of tetanus in horses in Australia.

OBJECTIVE: Identify veterinarians' practices, recommendations and perceptions when preventing tetanus in horses in Australia. METHODS: Graduated members of Equine Veterinarians Australia participated in an online survey about the prevention of tetanus in horses in Australia. RESULTS: Of 77 respondents (response rate ~ 8%), 50 (65%) reported that they had attended collectively 145-152 cases of tetanus in horses in Australia (1.1 cases of tetanus observed/10 veterinarian-years since qualification). The estimated case fatality rate (CFR) was at least 79%. Puncture wounds were most frequently suspected as the entry point (32%; n = 47). Five respondents (7%) reported cases of localised tetanus. Three respondents reported generalised tetanus within 2 weeks of tetanus antitoxin (TAT) administration. Respondents did not report any cases of tetanus in horses which had been vaccinated according to manufacturer's recommendations. All respondents recommended vaccination, but over 50% (N = 45) stated 'lack of veterinary recommendation' as often or sometimes a reason why clients did not vaccinate horses. Opinions varied on the use of TAT for peri-exposure prophylaxis; 67% of respondents dosed TAT independent of body weight, with the rest dosing according to body weight. Cases of Theiler's disease related to the use of TAT were not reported in Australia by respondents. DISCUSSION: The caseload of equine tetanus appears relatively low among equine veterinarians in Australia. Consistent with the literature, estimated CFR was high. Respondents' recommendations and perceptions about tetanus vaccination were generally consistent but varied regarding TAT usage. Evidence for TAT usage is limited and we recommend studies of TAT efficacy in horses.

The human metapneumovirus: a case series and review of the literature.

Human metapneumovirus (hMPV) is an emerging human pulmonary pathogen that is genetically related to respiratory syncytial virus. It has been increasingly associated with respiratory illnesses over the last few decades. Immunocompromised patients are particularly susceptible with resultant morbidity and mortality. We describe our experience with 9 immunocompromised patients diagnosed with pneumonia secondary to hMPV, 2 of whom were successfully treated with aerosolized and oral ribavirin along with intravenous immunoglobulin (IVIG). We suggest that hMPV should be considered in the differential diagnosis of immunocompromised patients with acute respiratory illness. Ribavirin (oral and aerosolized) with IVIG is potentially an effective treatment option for those with severe disease.

Chlamydia psittaci: a suspected cause of reproductive loss in three Victorian horses.

Chlamydia psittaci was detected by PCR in the lung and equine foetal membranes of two aborted equine foetuses and one weak foal from two different studs in Victoria, Australia. The abortions occurred in September 2019 in two mares sharing a paddock northeast of Melbourne. The weak foal was born in October 2019 in a similar geographical region and died soon after birth despite receiving veterinary care. The detection of C. psittaci DNA in the lung and equine foetal membranes of the aborted or weak foals and the absence of any other factors that are commonly associated with abortion or neonatal death suggest that this pathogen may be the cause of the reproductive loss. The detection of C. psittaci in these cases is consistent with the recent detection of C. psittaci in association with equine abortion in New South Wales. These cases in Victoria show that C. psittaci, and the zoonotic risk it poses, should be considered in association with equine reproductive loss in other areas of Australia.

Serological responses of Australian horses using a commercial duplex indirect ELISA following vaccination against strangles.

OBJECTIVE: To determine the nature of serological responses in Australian horses using a commercial duplex indirect ELISA (iELISA) following vaccination against strangles. DESIGN: A group (n = 19) of client-owned horses from five properties were recruited to receive a primary course of a Streptococcus equi subsp. equi (S. equi) extract vaccine. Serological responses were determined by duplex iELISA incorporating S. equi-specific fragments of two cell wall proteins, SEQ2190 and SeM (antigens (Ag) A and C, respectively). METHODS: The horses were administered a primary strangles vaccination course. Blood was collected immediately prior to each of the three vaccinations at 2-week intervals and additionally at 28 and 56 days following the 3rd vaccination (V3). RESULTS: Significant increases in mean antibody levels of horses following vaccination were limited only to AgC, which was significantly increased at T2/V3, 14 days following V2 (ratio of geometric means = 3.7; 95% confidence interval (CI): 1.6, 8.4; P = 0.003). There was no increase in mean antibody to Ag A (ratio of geometric means = 1.4; 95% CI: 0.6, 3.2; P = 0.39). Four horses (22%) exceeded the test cut-off for AgC following vaccination. CONCLUSION: Vaccination of Australian horses is unlikely to interfere greatly with detection of strangles using the duplex iELISA. No responses would be anticipated to AgA following vaccination with Equivac© S/Equivac© 2in1 and only a minority are likely to respond to AgC. We conclude that the results of this study validate the usefulness of the duplex iELISA to assist control measures for strangles outbreaks in Australian horse populations.

Disease suspected to be caused by Ross River virus infection of horses.

Ross River Virus (RRV) was believed to be the cause of acute illness in four horses around the Bellarine peninsula in south-west Victoria, Australia. The horses presented with clinical signs including petechial haemorrhages, lymphadenopathy, distal limb swelling and reluctance to move. Fibrinogen was also elevated in three of the four horses. Whilst no virus was isolated, serological testing revealed elevated RRV IgM titres in all horses indicating acute infection. The outbreak occurred at a time when a known RRV vector, the mosquito Aedes camptorhynchus was recorded at very high levels in the region. This report is one of very few to attribute specific signs of disease to RRV in horses in conjunction with serological evidence of infection.

Towards two-photon excited endogenous fluorescence lifetime imaging microendoscopy.

In situ fluorescence lifetime imaging microscopy (FLIM) in an endoscopic configuration of the endogenous biomarker nicotinamide adenine dinucleotide (NADH) has a great potential for malignant tissue diagnosis. Moreover, two-photon nonlinear excitation provides intrinsic optical sectioning along with enhanced imaging depth. We demonstrate, for the first time to our knowledge, nonlinear endogenous FLIM in a fibered microscope with proximal detection, applied to NADH in cultured cells, as a first step to a nonlinear endomicroscope, using a double-clad microstructured fiber with convenient fiber length (> 3 m) and excitation pulse duration (≈50 fs). Fluorescence photons are collected by the fiber inner cladding and we show that its contribution to the impulse response function (IRF), which originates from its intermodal and chromatic dispersions, is small (< 600 ps) and stable for lengths up to 8 m and allows for short lifetime measurements. We use the phasor representation as a quick visualization tool adapted to the endoscopy speed requirements.

Familial hyperthyroidism due to inappropriate thyrotropin secretion successfully treated with triiodothyronine.

A family of three generations is described in which six females had hyperthyroidism secondary to chronic overstimulation of the thyroid by pituitary TSH. In the untreated state, their basal levels of T4 ranged between 14-22 microgram/dl, T3 levels ranged from 205-300 ng/dl, T3 resin uptake ranged from 43-61%, TSH ranged from 5-26 microU/ml, and PRL ranged from 33-75 ng/ml. Basal metabolic rate (BMR) was elevated in all patients (+32 to +100%). There was no evidence of pituitary tumor, In spite of elevated circulating thyroid hormones, TRH stimulated TSH and PRL to 25-57 microU/ml and 120-300 ng/ml, respectively. Serum TSH could be suppressed to normal after 1 week of T3 administration (25 microgram three times per day). Concomitantly, serum T3 and T4 levels fell, and the TSH response to TRH became normal. In contrast, T4 (200 microgram/day) administered for 1 and 4 weeks, respectively, to two patients did not suppress the pituitary-thyroidal axis. A long term therapeutic trial was performed in three patients with T3 and a single morning dose of 25-50 microgram. TSH gradually returned to normal, as did thyroid hormone levels and the BMR. The clinical manifestations of hyperthyroidism regressed, and complete remission was achieved after 2-3 months of T3 therapy, which persists to data as long as medication is continued. The inappropriate TSH secretion of our patients appears to be due to partial unresponsiveness of the thyrotroph to thyroid hormone. It is suggested that either the pituitary T4 monodeiodinase is deficient in our patients, resulting in low intracellular T3 levels, or the thyrotroph has reduced sensitivity to T3 and therefore can shut off TSH only when serum T3 is raised to high levels, albeit intermittently.

Langerhans' cell histiocytosis (histiocytosis X): immunophenotype and growth fraction.

The immunophenotype and proliferation fraction have been investigated in 26 cases of Langerhans' cell histiocytosis (LCH). In all cases LCH cells were positive for S-100 protein, CD1a, or both. In most cases LCH cells expressed the macrophage-associated marker CD68 and in two cases they contained lysozyme. Expression of both cytoplasmic CD2 and CD3 was observed in cryostat sections. An unexpected finding was the presence of placental alkaline phosphatase in LCH cells. Langerhans' cells in normal skin were negative for both CD2 and CD3, but a proportion contained placental alkaline phosphatase. In four cases of Rosai-Dorfman disease the histiocytic cells, which share certain immunophenotypic properties with Langerhans' cells, also were positive for placental alkaline phosphatase. A significant proportion of LCH cells stained positively with the antibody to proliferating cell nuclear antigen and also with the proliferation marker Ki-S1. A good correlation between the percentage of Ki-67-positive and proliferating cell nuclear antigen- and Ki-S1-positive cells, respectively, was observed. Thus, in comparison with their putative precursors, LCH cells have an aberrant phenotype and are proliferating locally. This might suggest that LCH is a neoplastic rather than a reactive process.

The relationship between female sexual practices and the development of antisperm antibodies.

OBJECTIVE: To determine if female sexual practices are associated with the development of antisperm antibodies. DESIGN: Anonymous questionnaire. SETTING: Tertiary care; private practice. PATIENTS: Thirty-nine consecutive patients undergoing antisperm antibody testing; 32 responded. INTERVENTIONS: Cervical mucus and serum obtained at midcycle. MAIN OUTCOME: Female sexual practices were found not to be related to the development of antisperm antibodies. RESULTS: The percent (44.4) of women with antisperm antibodies who practice anal intercourse was not different from the percent (35.7) without these antibodies who engage in the same practice, and the percent (94.4) of women with antisperm antibodies who practice oral intercourse was not different from the percent (92.8) without these antibodies who engage in this practice. CONCLUSION: Female sexual practices do not appear to be related to the development of antisperm antibodies.

PIP: The role of antisperm antibodies in fertility is related but unknown. This study was designed to explore the relationship between anal and oral intercourse and the development of sperm antibodies in women. An anonymous self-administered questionnaire was given to 39 consecutive women tested for antisperm antibodies (Shulman method) postcoitally in an infertility practice, of whom 32 responded. 14 women had a negative test for sperm antibodies and 18 were positive with mucus and serum antibodies. The gelatin agglutination test is described and positivity was based on agglutination occurring at, at least, 1:4 dilution of inactivated serum with quantification for higher levels of sperm antibody formation. A negative response was no reaction at a 1:4 dilution. The tube-slide agglutination test was also performed to count the number of motile, free, and clumped cells: the % of activity was expressed as the number of clumped cells divided by the total number of cells. Cervical mucus aspirated on or near ovulation was sampled and tested using a modification of the tube-slide agglutination test. Since the nominal data were very small, the X-squared statistic was used to analyze the anal intercourse data. The hypothesis of differences was tested with a 2 x 2 contingency table. Since in the small sample of oral intercourse data the frequency cells were 5, Fisher's exact statistic was used; the 2 x 2 contingency table was constructed to test the hypothesis of differences. No significant association was found between oral or anal intercourse and the development of sperm antibodies in the female. It is pointed out that of all sexually active women exposed to spermatozoa vaginally, only 68% develop antibodies. This may occur because of a breakdown in the normal physical immunological barriers, or cervical or vaginal abrasion or cervicitis, or a defect in the immune system. Further study is ongoing in exploring the relationship between autoimmune responses and sperm antibodies. Although not statistically significant, the largest differences occurred between women practicing anal intercourse and ejaculating with and without antibodies. A larger sample of being constructed to determine whether sample size is a factor. Reduction of antigenic load is advised for infertile women.