Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

OBJECTIVES: To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). METHODS: This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. RESULTS: A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). CONCLUSIONS: Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

[Clinical research on immune checkpoint and head and neck squamous cell carcinoma].

T cell immune checkpoint pathways contribute to tumor immune escape. Many studies have shown that immune checkpoint is demonstrably correlated with tumor grade or prognosis in several types of malignancies and immune checkpoint has become a new biological index for tumor detection and prognosis. Immune checkpoint inhibitors have shown promising tumor outcomes in clinical trials for some advanced solid tumors and it will become a new target for cancer immunotherapy. In this review we will explore the correlation between expressions of immune checkpoint-associated genes and proteins in immune microenviroment and prognosis of head and neck squamous cell carcinoma, and specifically will discuss how this pathway can be manipulated with immune therapeutic drugs.

Aggressive fibromatosis of the larynx: case report and brief review.

Aggressive fibromatosis is a rare, benign, fibroblastic neoplasm, characterized by local invasion and a relatively high rate of recurrence. Here a case of laryngeal aggressive fibromatosis in a 47-year old man is reported. The patient presented with worsening dyspnoea and hoarseness and was hospitalized for treatment with partial laryngectomy. Final pathological evaluation of the tumour confirmed a diagnosis of aggressive fibromatosis. The patient has remained disease-free without further treatment for 5 years. This study demonstrated that aggressive fibromatosis may occur around the larynx and can be managed by partial laryngectomy alone. It is, therefore, important to include this rare disease entity in the routine differential diagnosis of laryngeal masses.

Microbiological profile of a shipboard environment and the flora on contact lenses of seamen.

PURPOSE: The purpose of this study was to culture and identify the spectrum of organisms (and their sensitivities) that contaminate the extended wear contact lenses of seamen in their working environment. A secondary aim was to identify the most appropriate first-line antibiotic regimen to be used on seamen who sustain contact lens-related corneal keratitis on board ship. METHODS: Twenty pairs of contact lenses of 20 seamen in one group and 24 pairs in another group wearing contact lenses were collected at the end of 1 week of extended wear. Groups one and two differed only in the way lenses were stored prior to culturing. All contact lenses were then brought to the microbiological lab within 24 hours for culture and sensitivity testing. RESULTS: The most common contaminants on the contact lenses in this study were Staphylococcus epidermidis and Staphylococcus aureus, organisms resident on the normal eyelids. Enterobacterand Pseudomonas species, present in a shipboard environment, were also identified as contaminants on the contact lenses. The organisms cultured from the contact lenses correlated well with those of normal lid flora as well as from the ship environment and are probably derived from these sources. Storage in saline-containing preservatives yielded significantly less positive bacterial cultures from the contact lenses in our study. All bacterial isolates were sensitive to ciprofloxacin whereas several bacteria resistant to cefazolin and gentamicin were identified. CONCLUSION: The most common contaminants on the contact lenses in this study were Staphylococcus epidermidis and Staphylococcus aureus, organisms resident on the normal eyelids. Enterobacter and Pseudomonas species, which are normally present in a shipboard environment, were also identified as contaminants on the contact lenses. Ciprofloxacin is effective against all organisms identified as contaminants on the contact lenses in this study. Of all the antibiotics tested, it is probably the most suitable agent against contact lensrelated keratitis under such shipboard circumstances and is thus recommended in these situations.

Polymorphism of the angiotensin-converting enzyme gene in patients with cerebral infarction in Koreans.

The relationship between cerebrovascular disease and an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is still being debated. The frequency of the DD genotype of the ACE gene was significantly higher in subjects with than those without cerebral infarction in Japan. The aim of the present study was to assess the relationship between ACE gene polymorphism and the development of cerebral infarction in a population from Korea. We examined its possible role as a risk factor in patients with cerebral infarction. The association between ACE gene polymorphism and cerebral infarction was examined in 106 patients with cerebral infarction and 498 controls without cerebral infarction. Frequencies of the genotypes and alleles of the ACE gene were investigated. The ACE genotype was analyzed by the polymerase chain reaction (PCR). The frequency of D allele was 37.7% in patients and 39.1% in controls (chi2 = 0.128, p = 0.720). The frequencies of the genotypes of the ACE gene were II: 39.6%, ID: 45.3%, and DD: 15.1% in patients, and II: 37.1%, ID: 47.6%, and DD: 15.3% in controls (chi2 = 0.127, p = 0.721). There was no significant difference in the frequency of the DD genotype of the ACE gene, and we did not find any association between ACE polymorphism and cerebral infarction. These results indicate that ACE polymorphism is not a risk factor for the development of cerebral infarction in a Korean population.

Effect of histamine on nasal epithelial permeability to horseradish peroxidase in allergic guinea pigs.

The effect of histamine and antigen on the permeability of nasal mucosa to macromolecules in allergic guinea pigs was investigated with a histochemical technique using horseradish peroxidase (HRP). We found that the ratio of intercellular spaces penetrated by HRP to the total number of intercellular spaces of the nasal epithelium in nonallergic groups was increased by histamine challenge dose-dependently. The HRP reaction products in the intercellular spaces in allergic groups were significantly increased by challenge with histamine at 5.4 x 10(-4) mol/L and 5.4 x 10(-2) mol/L, in contrast to nonallergic groups. We conclude that histamine increases nasal mucosal permeability, and this effect is most likely mediated by a functional change in the epithelial tight junctions.

Rheological properties of middle ear mucus in relation to goblet cell population in cat.

Seventeen mucoid middle ear effusions were collected from the tympanic cavity of 15 cats 1 or 2 weeks after tubal obstruction. Middle ear mucosa was also taken both from the tympanic cavity and bulla, and the number of goblet cells was counted. Both elasticity (G') viscosity (eta') of the mucoid effusion were determined with an oscillating sphere magnetic rheometer and compared with goblet cell count. There was a significant correlation between G' and goblet cell population in the tympanic cavity. A similar significant correlation was observed between eta' and goblet cells. The G' and eta' values of the mucoid mucus were much higher than the optimal viscoelasticity for mucociliary transport. Results indicate that the mucus obtained in this study mainly originated from the goblet cells, and that its viscoelasticity was beyond ideal values for mucociliary transport.

Rheological and biochemical properties of middle ear effusions from experimental otitis media in cats.

Both rheological and biochemical analyses were performed on middle ear effusions (MEEs) from cats with experimental otitis media with effusions (OME) induced by obstruction of the Eustachian tube. This study was undertaken in order to clarify the factors determining rheological properties (elasticity and viscosity) of MEEs. The viscoelasticity of the effusions had a positive significant correlation to fucose/total protein concentration (TPC), and a negative correlation to cathepsin B level/TPC. No correlation was observed between albumin level/TPC and viscoelasticity. These results indicate that in cats the rheological properties of MEEs depend on the level of secretory glycoproteins in MEEs and on the severity of inflammation in the early stage after tubal obstruction.

Effects of endotoxin and neutrophil lysate on experimental otitis media with effusion in cats.

Middle ear effusion (MEE) from otitis media with effusion (OME) contains large amounts of chemical mediators and substances from bacteria, which may act on the mucosa itself and cause further changes in the inflamed mucosa and MEE. To clarify the effects of such substances in MEE, we instilled endotoxin (LPS) or allogeneic neutrophil lysate (NL) into the middle ear cavity of OME induced by Eustachian tube obstruction (ETO). ETO + LPS and ETO + NL groups showed retention of a large amount of MEE as a characteristic difference between ETO alone group and these groups. The instillation of LPS into the middle ear cavity of the ETO model significantly increased the number of total cells and the ratio of the concentrations of albumin to total protein in MEEs. The instillation of NL significantly increased the number of goblet cells in the middle ear. These facts indicate that the pathology of OME may change in response to various factors added to MEE. Hence, we propose that a vicious circle of self-mediated inflammation is a possible causative factor for chronic OME.

The relationship between proteases activity and glycoprotein levels in middle ear effusions from experimental otitis media in cats.

The relationship between lysosomal proteases activity (elastase and cathepsin B) and levels of mucous glycoproteins in middle ear effusions (MEEs) was studied using a cat model of otitis media with effusion (OME) induced by Eustachian tube obstruction (ETO). The ratio of cathepsin B activity to total protein concentration (TPC) in MEE was 25.6 +/- 19.4 RFU/g x dl-1 at 1 week after ETO, and increased with the duration of OME. The ratio of elastase activity to TPC had a significant correlation to total leukocyte count. The ratio of fucose levels to TPC, which is one of the parameters reflecting levels of mucous glycoprotein, at 1 week after ETO was significantly higher than that at both 2 and 4 weeks after ETO. The percentage of glycoprotein levels absorbed to wheat germ lectin was highest at 1 week after ETO, and decreased with the duration of OME. In conclusion, mucous glycoproteins in cat occupy a larger portion of glycoproteins in MEE at the early stage of OME, and elastase and other lysosomal proteases may play a role in both stimulation of mucin release from goblet cells and mucin degradation. The balance of these processes seems to be a key factor determining mucin levels in MEEs.

A quantitative study of the ciliary area of experimental otitis media with effusion in cats.

A quantitative electron microscopic study was performed to determine the extent of the ciliary surface area of the middle ear epithelium in cats. In normal cats, 97.8% of the middle ear mucosa in the hypotympanum and 45.9% in the upper part of the bulla were covered by cilia. Eustachian tube obstruction (ETO) significantly reduced the ciliary area to 73.1% in the hypotympanum and to 16.2% in the upper part of bulla at 1 week after ETO. Instillation of Escherichia coli lipopolysaccharide (LPS) or cat polymorphonuclear leukocyte (PMN) lysate into the middle ear cavity followed by ETO did not reduce the ciliary area, compared with ETO induced alone. Our results indicate that ETO reduces the ciliary area of the middle ear mucosa and that LPS or neutrophils do not enhance reduction of the ciliary area compared to ETO induced alone in this experimental condition.

ELISA to determine immunoreactive Pseudomonas aeruginosa elastase in chronic suppurative otitis media.

A sensitive sandwich ELISA has been developed to measure the levels of Pseudomonas aeruginosa elastase (PE) in ear discharges from chronic suppurative otitis media (CSOM) patients. Preincubation of the sample with EDTA-2Na before ELISA was employed to inhibit PE activity which hydrolyzes the anti-PE IgG antibody into a smaller molecular form. The PE levels of 10 middle ear effusions (MEE) from chronic otitis media with effusion were also measured. In CSOM, 9 of 10 samples had significant PE levels, ranging from 6.8 to 62.1 micrograms/ml, which were significantly higher than those in MEE (p less than 0.01), the majority of which was below the detection limit. Two samples of CSOM with the P. aeruginosa infection showed high PE levels. This sandwich ELISA for the measurement of PE is a very sensitive method requiring only a small sample amount.

Quantitative histochemical study of secretory cells after short term tubal obstruction in the cat.

Quantitative histochemistry of goblet cells producing different types of glycoproteins was examined in cat middle ears with and without Euatachian tube obstruction (ETO). The goblet cell population significantly increased at 1 week after ETO and showed a tendency to decrease down to the normal level at 4 weeks after ETO. In the normal ears, approximately 85% of glycoprotein in the secretory cells were sulphated and 15% were neutral. ETO significantly increased goblet cell population containing sulphated glycoprotein at the expense of neutral glycoprotein. The results indicate that goblet cells can easily and within a short period be modified both in number and in intracellular glycoproteins by a tubal obstruction.

Neutrophil elastase and its complex with alpha 1-antitrypsin in soluble and insoluble fractions of nasal secretions of chronic sinusitis.

Immunoreactive neutrophil elastase (NE) and its complex with alpha 1-antitrypsin (AT) was measured by double antibody enzyme linked immunosorbent assay (ELISA) in nasal secretions of chronic sinusitis (CS). Nasal secretions were separated into two fractions: PBS-soluble and insoluble fractions. Elastolytic activity was also examined. Mean value of total NE level was 31.0 micrograms/ml in the soluble fraction, which was significantly lower than that in the insoluble fraction (71.9 micrograms/ml, p less than 0.01). On the other hand, the percentage of complexed NE in total NE in the soluble fraction (33.7%) was significantly higher than that in the insoluble fraction (12.1%, p less than 0.01). Elastolytic activity in the soluble fraction (23.4 RFU) was significantly lower than that in the insoluble fraction (170.5 RFU, p less than 0.01). NE with elastolytic activity exists in nasal secretions of CS, and active-free NE in the insoluble fraction could be a major source of enhancement and continuation of mucosal inflammation.

[Lectin histochemistry of primary and metastatic tumor cells of laryngeal cancer].

In order to clarify possible alterations of membrane-, and cytoplasma-glycoconjugates of laryngeal cancer cells in metastatic process, a histochemical study was performed on laryngeal squamous carcinoma, using seven lectins conjugated with horseradish peroxidase (HRP); PNA, UEA-I, WGA, RCA-I, DBA, SBA and MPA. The author studied 32 primary tumors and 32 corresponding metastatic tumors obtained from 32 patients and primary tumors from 8 patients without histological evidence of lymph node metastasis. None of the patients underwent irradiation or chemotherapy before operation. The specimens were provided for routine lectin histochemistry. The present study revealed some significant differences in lectin-binding as follows. Primary tumor vs. metastatic tumor: There was a significant difference in lectin-binding between primary and metastatic cancer cells. 29 (90.0%) of 32 primary tumors were positive for MPA-staining. On the other hand, 21 (65.6%) of 32 metastatic tumors were positive for MPA-staining. There was a statistically significant (p less than 0.05) difference between primary and metastatic tumors with regard to MPA-binding. Primary tumor cells tended to more bind with lectins than with metastatic tumor cells. Well-differentiated primary tumor vs. moderately differentiated primary tumor: There was a significant difference in lectin-binding between these two types of tumors. Of 15 well-differentiated primary tumors, 13 (86.7%) showed SBA binding. The percentage of SBA-binding was significantly higher in well-differentiated tumor than in moderately differentiated primary tumors (50%, 8/16). Keratinization vs. non-keratinization: There was a significant difference in lectin-binding between keratinized and non-keratinized tumor cells in both primary and metastatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adherence of Haemophilus influenzae to nasal, nasopharyngeal and buccal epithelial cells from patients with otitis media.

Since mucosal colonization may be an important determinant in the pathogenesis of otitis media with effusion (OME), we studied the adherence of Haemophilus influenzae (HI) to human nasal, nasopharyngeal, and buccal mucosal cells obtained from patients with OME. Non-typeable HI adhered in significantly greater numbers than type b HI. HI bacteria adhered to both nasal and nasopharyngeal mucosal cells in significantly greater numbers than to buccal ones. Non-typeable HI adhered to the epithelial cells from children with chronic sinusitis in more significant numbers than did those from children without chronic sinusitis. These results indicate that non-typeable HI adhere more readily to epithelial cells and that the nasal and nasopharyngeal mucosa may be an important route for HI infection in OME.

[Electron microscopic study of glycoconjugate in nasal mucosa of nasal allergy by lectin histochemistry].

Glycoconjugates in glandular and goblet cells of nasal mucosa were compared between normal and nasal allergy by using various horseradish peroxidase (HRP)-conjugated lectins; WGA, PNA, UEA-I and RCA-I. Specific sugar residues of glycoconjugates could be identified under electron microscope. Golgi's complex of the serous secretory cells in nasal allergic mucosa had positive staining in UEA-I. Goblet cells of nasal allergic mucosa were stained strongly in PNA, compared to normal mucosa, however, they were stained weakly in WGA. In conclusion, glycoconjugates in glandular and goblet cells seem to be changed in nasal allergy.

[Electron microscopic study of intercellular junction in nasal mucosa of nasal allergy by lectin histochemistry].

To explain of the mechanism of the enhanced nasal epithelial permeability to HRP in patients with nasal allergy, the inferior turbinate mucosa was removed from 6 normal adults and 7 adults with nasal allergy. Difference of the fine structure of the intercellular junction was compared between normal mucosa and mucosa of nasal allergy by electron microscope. Staining pattern of four kinds of HRP-conjugated lectin (HRP-WGA, PNA, UEA-I and RCA-I) was also studied by electron microscope. There was no significant difference in the intercellular space of the mucosa between the normal mucosa and mucosa of nasal allergy. In the epithelial cell membrane, pattern of HRP-lectin staining was almost similar in both groups. In normal nasal epithelium, the intercellular junction consisted of junctional complex; adherent junction, desmosome and gap junction. The intercellular space was approximately 150-250 A in width. The tight junction was located beneath the luminal surface of the epithelium, and belt-like continuation connecting the adjacent cells. It was concluded that enhanced permeability to HRP in nasal allergy was not morphologic changes of the intercellular junction and component and distribution of the glycoconjugates in epithelial cellular membrane, but this may be based on functional changes.

Anaplastic small cell carcinoma of the larynx.

Anaplastic small cell carcinoma of the larynx is an uncommon neuroendocrine tumor. We report a case of this neoplasm of a 53-year-old male. The patient showed persistent hyponatremia accompanied with continuous loss of sodium in the urine, which resulted from inappropriate secretion of antidiuretic hormone (ADH). It is postulated that hyponatremia in this case was due to production of ADH by the tumor cells.