Ethanol endometrioma sclerotherapy: safety through 8 years of experience.

STUDY QUESTION: What are the complications of transvaginal ethanol sclerotherapy for the treatment of endometriomas? SUMMARY ANSWER: Sclerotherapy is a reliable, minimally invasive method applicable in outpatient procedures but with specific and potential life-threatening complications that need to be identified and prevented. WHAT IS KNOWN ALREADY: There are currently few data on the use of transvaginal ethanol sclerotherapy, and we mainly note septic complications. STUDY DESIGN, SIZE, DURATION: A retrospective observational cohort study was carried out. The study was conducted at an academic hospital and included 126 women aged 31.9 ± 5.5 years (mean ± SD), between November 2013 and June 2021. We analyzed a total of 157 ethanol sclerotherapy treatment (EST), treated by 131 EST procedures, in 126 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included women with an indication for transvaginal ethanol sclerotherapy. Indications were women with at least one endometrioma over 10 mm, isolated or associated with other endometriosis locations, requiring treatment for pain or infertility before assisted reproductive treatment. We followed a standardized transvaginal ethanol sclerotherapy procedure consisting of an ultrasound-guided transvaginal puncture of one or more endometriomas under general anesthesia. The cyst content was completely removed and flushed with saline solution. Ethanol (96%) was injected at 60% of the initial volume of the endometrioma, remained in the cyst for 10 min and was then completely removed. Ethanol loss was defined as a loss of 5 ml or more than 10% of the initial volume of the injected ethanol. Failure was defined by the contraindication of endometrioma puncture because of interposition of the digestive tract, ethanol loss in the previous endometrioma treated (in case of multiple ESTs), failure to aspirate the endometriotic fluid, contraindication to start ethanol injection owing to saline solution leakage, or contraindication to continue ethanol injection owing to suspicions of ethanol leakage at sonography. Intraoperative complications were defined by ethanol loss, positive blood alcohol level, and ethanol intoxication. Postoperative complications were defined by fever, biological inflammatory syndrome, and ovarian abscess. Complications were classified according to the Clavien and Dindo surgical classification, which is a system for classifying postoperative complications in five grades of increasing severity. MAIN RESULTS AND THE ROLE OF CHANCE: We reported a total of 17/157 (10.8%) transvaginal ethanol sclerotherapy failures during 14/131 (10.7%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. In the same sets of data, complication was reported for 15/157 (9.5%) transvaginal ethanol sclerotherapy in 13/131 (9.9%) transvaginal ethanol sclerotherapy procedures in 13/126 (10.3%) women. Nine of 126 women (7.1%) had a grade I complication, one (0.8%) had a grade II complication (medical treatment for suspicion of pelvic infection), two (1.6%) had a grade III complication (ovarian abscess) and one (0.8%) had a grade IV complication (ethanol intoxication). We did not observe any grade V complications. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study and pain assessment not considered. The benefit-risk balance of endometrioma transvaginal ethanol sclerotherapy was not evaluated. WIDER IMPLICATIONS OF THE FINDINGS: Our study is the first to evaluate the complications of transvaginal ethanol sclerotherapy with such a large cohort of women in a standardized protocol. Transvaginal ethanol sclerotherapy seems to be an effective alternative to laparoscopic surgery in the management of endometriomas and limits the alteration of ovarian reserve. Transvaginal ethanol sclerotherapy is a reliable, minimally invasive method applicable on an outpatient basis. The majority of complications are Clavien-Dindo ≤IV, for which preventative measures, or at least early diagnosis and treatment, can be easily performed. The risk of ethanol intoxication is rare, but it is a life-threatening risk that must be avoided by appropriate implementation and promotion of the sclerotherapy procedures. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: Aix Marseille University's ethics committee registration number 2021-06-03-01.

Detection of free-living amoebae in domestic cats with and without naturally-acquired keratitis.

Pathogenic free-living amoebae, most notably Acanthamoeba spp., are important pathogens of the human cornea. The importance of infection with free-living amoebae in cats with keratitis is currently unclear. The aim of this study was to determine the frequency of amoeba detection in corneas of cats with naturally-acquired keratitis and in the ocular surface microflora of cats without ocular disease. Clinical ophthalmic and in vivo corneal confocal microscopic examinations were performed on 60 cats with keratitis. Corneal scrapings were analyzed by amoeba culture; cytological evaluation; and Acanthamoeba, Hartmannella, and Vahlkampfia PCR assays. Following ophthalmic examination, conjunctival specimens collected from 60 cats without clinically apparent ocular disease were analyzed similarly. In one cat with ulcerative keratitis, amoeba cysts and trophozoites were detected by in vivo corneal confocal microscopy; an Acanthamoeba sp. was isolated from corneal specimens and detected by Acanthamoeba PCR assay; and suppurative corneal inflammation was present cytologically. An Acanthamoeba sp. was isolated from conjunctival specimens from one cat without clinically apparent ocular disease, but with suppurative inflammation demonstrated cytologically. Both Acanthamoeba isolates belonged to the T4 genotype. Naegleria-like amoebae were isolated in samples from two cats with keratitis and seven cats without clinical ocular disease, but amoebae were not detected by the other assays in these samples. Amoeba detection by culture was significantly (P = 0.01) associated with cytologically diagnosed corneoconjunctival inflammation. This study identified naturally-acquired Acanthamoeba keratitis in cats. Detection of Naegleria-like amoebae in samples from cats with and without keratitis is of uncertain pathological significance.

Cryptosporidium parvum: determination of ID50 and the dose-response relationship in experimentally challenged dairy calves.

The objectives were to determine the median infective dose (ID50) of Cryptosporidium parvum and to describe the dose-response relationship including associated clinical illness in experimentally challenged dairy calves. Within the first 24h of life, 27 test calves were experimentally challenged with C. parvum oocysts and 3 control calves were sham dosed. Test calves received 1 of 8 possible doses (25, 50, 100, 500, 1 × 10(3), 1 × 10(4), 1 × 10(5), and 1 × 10(6) oocysts). All 27 test calves developed diarrhea. Fecal oocyst shedding occurred in 25 (92.6%) test calves and in 0 control calves. The 2 non-shedding test calves both received 25 oocysts. There was an inverse relationship between dose and time to onset of fecal oocyst shedding (P=0.005). There was no relationship found between dose and duration (P=0.2) or cessation (P=0.3) of fecal oocyst shedding. In addition, there was not a significant relationship between log-dose and the log-peak oocysts (P=0.2) or log-total oocysts (P=0.5) counted/g of feces across the dose groups. There was a positive dose-response relationship between log-dose and diarrhea (P=0.01). However, when controlling for other factors, such as onset and cessation of fecal oocyst shedding, dose was not a significant predictor of diarrhea (P=0.5). Onset and cessation of fecal oocyst shedding were found to be the best predictors of diarrhea (P=0.0006 and P=0.04, respectively). The ID50 for fecal oocyst shedding was 5.8 oocysts, for diarrhea was 9.7 oocysts, and for fecal oocyst shedding with diarrhea was 16.6 oocysts. Given that the ID50 of C. parvum is far less than would be excreted into the environment by a naturally infected calf, prevention and control of cryptosporidiosis is a formidable challenge.

Comparison of 4 Giardia diagnostic tests in diagnosis of naturally acquired canine chronic subclinical giardiasis.

BACKGROUND: The performance of Giardia diagnostic tests that detect either cysts or fecal antigens has not been thoroughly examined. HYPOTHESIS/OBJECTIVES: We examined the concordance and agreement among 4 Giardia diagnostic tests (2 cyst and 2 coproantigen detection methods) in a colony of dogs chronically and subclinically infected with Giardia. ANIMALS: Twenty dogs with chronic, subclinical Giardia infection. METHODS: Giardia diagnostic tests were performed repeatedly on each dog over 120 days. Fecal cyst detection methods (ZnSO4 flotation and fluorescent antibody [FAB] coproscopy) were performed 3 times per week. Coproantigen methods (Giardia SNAP test and quantitative ELISA) were performed weekly. Results were analyzed and compared among methods. RESULTS: When compared with FAB coproscopy, all of the in-house diagnostic tests had excellent positive predictive values (PPVs, 95-99%) at the study prevalence (89%). At lower prevalence rates, ZnSO4, SNAP, and ELISA tests all had good negative predictive values (NPVs), but poor PPVs. There was poor to good agreement among tests by kappa analysis. CONCLUSION AND CLINICAL RELEVANCE: Our findings show that most commonly used in-house Giardia diagnostic tests have poor agreement with the gold standard method (FAB coproscopy). The in-house tests have good NPVs, but poor PPVs, at prevalence rates common in most clinical settings.

Influence of Enterococcus faecium SF68 probiotic on giardiasis in dogs.

BACKGROUND: Giardiasis is a common, potentially zoonotic disease, and dogs often harbor and shed cysts without showing clinical signs. Treatment with the probiotic Enterococcus faecium SF68 has been shown to stimulate mucosal and systemic immunity in a variety of animal models and in young dogs, and to reduce giardial cyst and antigen shedding in rodents. HYPOTHESIS: Adult dogs with chronic naturally acquired giardiasis will have decreased giardial fecal cyst and antigen shedding and increased innate and adaptive immunity after 6 weeks probiotic treatment with E. faecium SF68. ANIMALS: Twenty adult dogs. METHODS: After a 6-week dietary equilibration period, dogs were randomized to receive E. faecium SF68 or placebo for 6 weeks, and then crossed over to the alternate treatment. We measured cyst shedding, fecal giardial antigen, fecal immunoglobulin A (IgA) concentration, and circulating leukocyte phagocytic activity at multiple timepoints to determine the effect of E. faecium SF68 on giardiasis and immune responses in these dogs. RESULTS: No differences were observed between placebo or E. faecium SF68 treatment for giardial cyst shedding, fecal antigen shedding, fecal IgA concentration, or leukocyte phagocytic activity. CONCLUSIONS: Short-term treatment with E. faecium SF68 of dogs with chronic naturally acquired subclinical giardiasis fails to affect giardial cyst shedding or antigen content and does not alter innate or adaptive immune responses.

Fluctuations of serum IgA and its subclasses in allergic bronchopulmonary aspergillosis.

Exacerbations of allergic bronchopulmonary aspergillosis (ABPA) are characterized by chest roentgenographic infiltrates, peripheral blood eosinophilia, and elevation of total serum IgE. Also elevated are serum immunoglobulin antibodies directed against Aspergillus fumigatus, IgE-Af, serum IgG-Af, and serum IgA-Af. We measured serum IgA-Af, IgA1-Af, and IgA2-Af by ELISA to determine whether elevations of IgA-Af occurred before or during an exacerbation (like IgG-Af) or after (like IgE-Af). Ten exacerbations of ABPA were studied in seven patients with an average of 10 serial sera per patient analyzed. We used an indirect amplified ELISA with Af initially sensitizing microtiter wells. A "serologic" rise of immunoglobulin Af was identified when optical densities were twice the baseline sera. Serum IgA-Af was elevated over baseline before (n = 5) and during (n = 1) the time of an exacerbation. Serum IgA1-Af was elevated over baseline before (n = 5) or at the time (n = 5) of an exacerbation in all 10 cases. Serum IgA2-Af was elevated before (n = 2) and during (n = 5) exacerbations. Analogous to total serum IgE and IgG-Af, these experiments demonstrate substantial elevations of serum IgA-Af, IgA2-Af, and particularly, IgA1-Af before or during exacerbations characterized by roentgenographic infiltrates. The data are consistent with a contributory role of IgA-Af in the pathogenesis of ABPA.

The effects of age on isotypic antibody responses to Aspergillus fumigatus: implications regarding in vitro measurements.

The demonstration of elevated serum immunoglobulin E (IgE), immunoglobulin G (IgG), and immunoglobulin A (IgA) antibodies to Aspergillus fumigatus (Af) is a valuable aid in the serodiagnosis of allergic bronchopulmonary aspergillosis (ABPA). It is important to recognize cases of ABPA, because repeated untreated episodes of pulmonary infiltrates can result in bronchiectasis and even fatal fibrotic lung disease. Serum samples from patients with ABPA have increased isotypic antibodies to Af when compared with patients with asthma and immediate cutaneous reactivity but in whom ABPA has been excluded. There is little information regarding age-related changes of isotypic antibodies to a specific allergen or in comparison of such changes with age-related changes in total class-specific antibody. We determined IgE-Af, IgG-Af, and IgA-Af and total IgE, IgG, and IgA concentrations in serum samples from children with asthma (ages less than 1 through 5 years, 6 through 10 years, and 11 through 15 years) and compared the results with those in children with APBA and adults with asthma. The use of an indirect amplified ELISA with Af adsorbed to microtiter wells demonstrated that serum samples from children with ABPA have elevated IgE-Af, IgG-Af, and IgA-Af concentrations compared with those in serum samples from children with asthma. The assays were sensitive and highly specific in discriminating ABPA from asthma in children. Isotypic antibodies to Af in children do not demonstrate age-related increases as occur for total serum IgE, IgG, and IgA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of cross-reactivity between IgE to salmon and protamine sulfate.

Immediate type-generalized reactions to protamine sulfate are uncommon but may be fatal. The mechanisms of severe or fatal reactions are unknown in most cases. One theory is that contaminating fish (salmon) proteins present in protamine solutions induce anaphylaxis in salmon-sensitive subjects. A second hypothesis is that protamine interacts with anti-salmon IgE to cause anaphylaxis. We assessed these hypotheses by establishing an indirect amplified enzyme-linked immunosorbent assay (ELISA) for IgE to salmon. Sera obtained from two subjects anaphylactically sensitive to salmon demonstrated high binding to salmon that was not inhibited by preincubation of sera with 500 or 1000 micrograms of protamine or Aspergillus fumigatus. Serum from a patient who experienced anaphylactic shock from protamine was indistinguishable from control sera in the ELISA for IgE to salmon. Anti-protamine IgE could not be demonstrated in separate experiments. The assays prove that 1) serum IgE to salmon is not inhibited by protamine and 2) serum from a patient experiencing a severe reaction to protamine did not contain IgE to salmon or protamine. The experiments do not support the notion that there is cross-reactivity between IgE to salmon and protamine sulfate in the cases evaluated.

Prospective immunologic and clinical study of a population exposed to hexamethylene diisocyanate.

We have prospectively evaluated 150 workers exposed to hexamethylene diisocyanate (HDI) and its trimer (THDI) during an 18-month period. The evaluation consisted of periodic serum antibody studies and a questionnaire that was designed to attempt to identify symptoms compatible with work-related syndromes of allergic rhinitis, allergic conjunctivitis, hypersensitivity pneumonitis, asthma, or irritant reactions. The study population was divided into seven groups on the basis of job classification. The groups differed in exposure levels but were similar in terms of age, sex, smoking history, and duration of work with isocyanates. IgE and IgG against HDI and THDI conjugated to human serum albumin (HSA) (HDI-HSA and THDI-HSA) were determined by ELISA. There were no instances of immunologically induced disease among the 21% of workers in this sample with antibody; however, there is insufficient evidence at this time to make judgments about the relationship between antibody and clinical disease. The antibody was generally low-level IgG that may be a sensitive indicator to detect exposure to certain reactive chemicals. The level of antibody was not different among job classes or between smokers and nonsmokers. Moreover, there was no correlation between antibody level and exposure duration in these workers whose exposure levels are all well below National Institute for Occupational Safety and Health recommendations. Further evaluation will extend these observations.

Analysis of bronchoalveolar lavage in allergic bronchopulmonary aspergillosis: divergent responses of antigen-specific antibodies and total IgE.

Bronchoalveolar lavage (BAL) was performed in eight patients with allergic bronchopulmonary aspergillosis (ABPA) at a time when chest roentgeongraphy did not reveal an infiltrate, and respiratory status was stable. BAL was tolerated well by all patients with only one patient experiencing mild wheezing. BAL fluid recovery averaged 40%, and total cells/lavage were 22.3 x 10(6) (range 3.5 to 49.5 x 10(6)). Cell viability, as determined by trypan blue exclusion, averaged 48% (range 34% to 60%). Mean values for cellular elements were macrophages, 62%; epithelial cells, 12%; lymphocytes, 16%; neutrophils (PMN), 4%; and eosinophils, 6%. Isotypic antibodies to Aspergillus fumigatus (Af) in BAL and serum were detected by an amplified indirect ELISA. Antibodies to Af in BAL expressed as optical density/albumin (milligrams per milliliter) were compared to BAL from six nonatopic patients. IgE-Af and IgA-Af in BAL were elevated in patients with ABPA compared with six nonatopic patients. The ratios of Ig-Af in BAL to peripheral blood in patients with ABPA were 48 (range 18 to 75) for IgE-Af, 96 (range 37 to 159) for IgA-Af, and 0.94 (range 0.24 to 1.40) for IgG-Af, suggesting local production of IgE-Af and IgA-Af in the bronchoalveolar compartment. Total serum IgE correlated directly with IgE-Af in BAL (rs = 0.67; p less than 0.02). However, the ratio of total BAL IgE/albumin divided by total serum IgE/albumin was 0.93 +/- 0.94, suggesting that the bronchoalveolar compartment is not the source of the significant elevations in total serum IgE in ABPA.

Immune responses to Aspergillus in cystic fibrosis.

Aspergillus fumigatus (Af) is well recognized in its ability to colonize the respiratory tract in cystic fibrosis (CF). Furthermore, a number of the immune responses of the patient with CF to this organism have been characterized, and the immune inflammatory response to Af may result in allergic bronchopulmonary aspergillosis (ABPA). This study evaluated a series of immunologic parameters in 75 patients with CF in order to characterize more fully the spectrum of immune responses of those patients to Af and to clarify the relationship of those responses to the clinical features of ABPA. The patients could be classified into four groups, depending on the clinical and immunologic findings. Eight (10.7%) of the 75 patients had clinical and laboratory evidence of ABPA, including immediate cutaneous reactivity to Af, eosinophilia, elevated total serum IgE, elevated serum IgE-Af or IgG-Af, and precipitating antibody to Af. Ten (13.3%) patients had these features, except that the total serum IgE level was within the normal range. Forty (53.5%) of the patients had no significant criteria for ABPA but had varying immunologic responses to Af, such as immediate cutaneous reactivity to Af in 25 patients and elevated serum IgE-Af and/or IgG-Af in 19 patients. Seventeen (22.7%) patients had no evidence of an immunologic response, as determined by skin testing and serologic assays. The study demonstrated that the response of patients with CF to Af ranges from clinically apparent ABPA to a possible variant of ABPA, to a nondiagnostic group of features consistent with sensitization to Af or to no characteristic immune response.

Allergic bronchopulmonary candidiasis: case report and suggested diagnostic criteria.

A patient with an illness consistent with allergic bronchopulmonary candidiasis is described. The patient had asthma, atelectatic pulmonary infiltrates on three occasions, immediate cutaneous reactivity as low as 10(-7) (wt/vol) to Candida albicans extract, and precipitating antibody to this organism. C. albicans was the only organism cultured from two bronchial lavage specimens. Total serum IgE was elevated to 5745 ng/ml and decreased rapidly with corticosteroid therapy. Serologic studies were not consistent with allergic bronchopulmonary aspergillosis. Serum IgE to C. albicans, measured by ELISA after adsorption of IgG from the serum samples by incubation with staphylococcal protein A, was found to be 575% to 650% above control values. The serum IgE antibody activity against Candida decreased with clinical improvement after corticosteroid therapy.

Prolonged evaluation of patients with corticosteroid-dependent asthma stage of allergic bronchopulmonary aspergillosis.

Eight cases with stage IV allergic bronchopulmonary aspergillosis (ABPA) (corticosteroid-dependent asthma stage) were observed for a total of 82 patient years with individual patients observed for 7 to 19 years (mean 10.2) years. One case is the first case of ABPA diagnosed in the United States in 1967. A second case has been observed through four stages of ABPA. None of these eight cases has demonstrated pulmonary deterioration by clinical, chest roentgenogram, or pulmonary function analysis. After diagnosis, the maintenance dose of prednisone in seven of eight cases was a low to moderate dose alternate-day prednisone. These results suggest that continuous observation and management of episodes of pulmonary consolidation or asthma exacerbations may prevent the progression of ABPA to stage V (fibrotic end stage). The total IgE may remain elevated in these patients, and therapy should not attempt to reduce total serum IgE to normal levels. After prolonged therapy with prednisone for asthma and control of ABPA, the IgE and IgG antibody indices against Aspergillus fumigatus may remain elevated or may be below the levels that are of diagnostic value.

Selection of mutations that alter the osmotic control of transcription of the Salmonella typhimurium proU operon.

We isolated 60 independent mutations, designated osmX, in Salmonella typhimurium that result in constitutive expression of the normally osmoregulated proU operon. Each of the osmX mutations is closely linked to the proU locus and cis-dominant over the osmX+ allele in diploid strains. These results suggest that the mutations are probably in the 5' transcriptional control region of the proU operon. Our failure to obtain either recessive or unlinked mutations that altered the osmotic control of transcription of the proU operon suggests that transcriptional regulation of the gene is not under the negative control of a repressor protein that is dispensable for cell viability. We discuss possible models for the mechanism of osmotic regulation of transcription of the proU operon.

Stage V (fibrotic) allergic bronchopulmonary aspergillosis. A review of 17 cases followed from diagnosis.

A review of the records of 17 patients with stage V (fibrotic stage) allergic bronchopulmonary aspergillosis observed since initial diagnosis (mean observation period, 4.9 years) demonstrated that, of the 11 surviving patients, four have very severe respiratory impairment. The other seven patients have mild or moderate functional impairment, but most of these have not shown clinical deterioration during the observation period. The occurrence of new roentgenographic infiltrates after the time of diagnosis was observed in only one patient in this series. Serum IgE and IgG levels against Aspergillus fumigatus, when compared with those of a control pool of serum samples from asthmatic patients with immediate cutaneous reactivity to Aspergillus, were the most useful immunologic studies diagnostically. Lung biopsy specimens obtained in five patients were of relatively little diagnostic value. All patients have required long-term prednisone therapy for control of asthma. Those patients whose forced expiratory volume in 1 s (FEV1) remained less than or equal to 0.8 L after initial corticosteroid treatment demonstrated a poor prognosis. When only moderate lung damage has occurred at the time of diagnosis, a stable subsequent course may be expected even in patients with stage V disease.

Serum IgA antibodies to Aspergillus fumigatus in various stages of allergic bronchopulmonary aspergillosis.

With double antibody ELISA, serum IgA antibodies against Aspergillus fumigatus (Af) were measured from patients in stages I through V allergic bronchopulmonary aspergillosis (ABPA). All sera from patients with ABPA demonstrated considerably greater values for IgA-Af than sera from nonatopic subjects. When this sera was compared with sera from patients with asthma and immediate cutaneous reactivity to Aspergillus, the present studies documented markedly elevated serum IgA-Af in the acute, exacerbation, and fibrotic stages of ABPA. Some patients in remission or corticosteroid-dependent asthma stages also demonstrated increased values. Because the major stimulus to antibody production occurs in the lung in response to presence of Af hyphae, polymeric IgA antibodies could potentially contribute to immunologic lung damage in ABPA. Finally, large dose alternate day or daily prednisone that was administered to patients in the fibrotic stage of ABPA did not prevent the marked production of isotypic antibodies to Af.

Allergic bronchopulmonary aspergillosis. Natural history and classification of early disease by serologic and roentgenographic studies.

Eighty-four patients with allergic bronchopulmonary aspergillosis (ABPA) were evaluated for a total of 294 patient-years with a mean observation period of 3.7 years and classified by the stage of ABPA. The largest percentage of patients were in the stage IV (corticosteroid-dependent asthma stage) group. The next largest percentage were in the stage V (fibrotic, end-stage lung disease) group. Of the latter 24 patients, eight had died. In addition, we describe 13 patients with all serologic characteristics of ABPA but without central bronchiectasis. We propose that these patients have seropositive ABPA and represent the earliest cases of it that can be diagnosed in contrast with ABPA with central bronchiectasis in which lung damage is already present.