Pilot study of women's perspectives when abnormal uterine bleeding occurs during perimenopause.

OBJECTIVE: We gained insights into women's experiences and knowledge about the occurrence of vaginal bleeding during perimenopause requiring evaluation. METHODS: Qualitative inquiry was chosen to explore topics in greater depth to understand individuals' experiences. Interviews with individuals were chosen due to the sensitive nature of gynecologic symptoms and management. Interviews were completed following gynecologic care to explore individuals' experiences with the evaluation and management of vaginal bleeding during perimenopause. RESULTS: Twelve individuals were interviewed between December 2019 and March 2020. Patient uncertainty about the medical significance of developing vaginal bleeding during perimenopause was associated with self-appraisal and gathering information from multiple sources. This experience of seeking evaluation and treatment resulted in varying degrees of trust concerning information received within or outside the clinic. Regarding new technologies that could replace the current invasive tests performed for diagnosis (i.e. ultrasound, hysteroscopy and biopsy), most women preferred the smartphone app and tampon home collection option. CONCLUSIONS: The experience of irregular or heavy vaginal bleeding during perimenopause is fraught with ambiguity, feelings of uncertainty about how to make sense of symptoms and inevitably begins with a period of self-appraisal.

Brincidofovir treatment of acyclovir-resistant disseminated varicella zoster virus infection in an immunocompromised host.

Brincidofovir (BCV) is a broad-spectrum antiviral agent active in vitro against double-stranded DNA viruses including herpesviruses, adenoviruses, polyomaviruses, and poxviruses. We report successful BCV use in management of disseminated acyclovir- and cidofovir-resistant varicella zoster virus in an immunocompromised hematopoietic stem cell transplant patient with chronic graft-versus-host disease who was intolerant to foscarnet.

Comparison of RNA isolation methods from insect larvae.

Isolating RNA from insects is becoming increasingly important in molecular entomology. Four methods including three commercial kits RNeasy Mini Kit (Qiagen), SV Total RNA isolation system (Promega), TRIzol reagent (Invitrogen), and a cetyl trimethylammonium bromide (CTAB)-based method were compared regarding their ability to isolate RNA from whole-body larvae of Thaumatotibia leucotreta (Meyrick), Thanatophilus micans (F.), Plutella xylostella (L.), and Tenebrio molitor (L.). A difference was observed among the four methods regarding RNA quality but not quantity. However, RNA quality and quantity obtained was not dependent on the insect species. The CTAB-based method produced low-quality RNA and the Trizol reagent produced partially degraded RNA, whereas the RNeasy Mini Kit and SV Total RNA isolation system produced RNA of consistently high quality. However, after reverse transcription to cDNA, RNA produced using all four extraction methods could be used to successfully amplify a 708 bp fragment of the cytochrome oxidase I gene. Of the four methods, the SV Total RNA isolation system showed the least amount of DNA contamination with the highest RNA integrity number and is thus recommended for stringent applications where high-quality RNA is required. This is the first comparison of RNA isolation methods among different insect species and the first to compare RNA isolation methods in insects in the last 20 years.

Advantages of using development models of the carrion beetles Thanatophilus micans (Fabricius) and T. mutilatus (Castelneau) (Coleoptera: Silphidae) for estimating minimum post mortem intervals, verified with case data.

Some beetles are as useful as blow flies for estimating the minimum post mortem interval (PMImin) or time since death. Examples include Thanatophilus micans (Fabricius) and Thanatophilus mutilatus (Castelneau), two geographically and ecologically overlapping African beetles. Molecular means of identifying these species, descriptions of their natural history, thermal summation models for the development of each species, and a case in which T. micans was recovered are presented. These beetles colonise bodies soon after death, their development spans more time than that of flies, and they may be little affected by maggot-generated heat. From an experimental perspective, they can be reared individually, which allows the identification of sick individuals and has analytical advantages relative to fly larvae that must be reared in groups. Estimating minimum post mortem intervals for both species using the case data strongly suggests that developmental models parameterised for one species should not be used to make forensic estimates for closely related species for which no specific model is available and emphasises the need for correct identifications.

Potential bias in the bank: what distinguishes refusers, nonresponders and participants in a clinic-based biobank?

BACKGROUND: Biobanks are an important resource for genetic and epidemiologic research, but bias may be introduced if those who accept the recruitment invitation differ systematically from those who do not in terms of attributes important to health-related investigations. To understand potential bias in a clinic-based biobank of biological samples, including genetic data linked to electronic health record information, we compared patient characteristics and self-reported information among participants, nonresponders and refusers. We also compared reasons for nonparticipation between refusers and nonresponders to elucidate potential pathways to reduce nonparticipation and any uncovered bias. METHODS: We mailed recruitment packets to 1,600 adult patients with upcoming appointments at Mayo Clinic (Rochester, Minn., USA) and recorded their participation status. Administrative data were used to compare characteristics across groups. We used phone interviews with 26 nonresponders and 26 refusers to collect self-reported information, including reasons for nonparticipation. Participants were asked to complete a mailed questionnaire. RESULTS: We achieved 26.2% participation (n=419) with 12.1% refusing (n=193) and 61.8% nonresponse (n=988). In multivariate analyses, sex, age, region of residence, and race/ethnicity were significantly associated with participation. The groups differed in information-seeking behaviors and research experience. Refusers more often cited privacy concerns, while nonresponders more often identified time constraints as the reason for nonparticipation. CONCLUSION: For genomic medicine to advance, large, representative biobanks are required. Significant associations between patient characteristics and nonresponse, as well as systematic differences between refusers and nonresponders, could introduce bias. Oversampling or recruitment changes, including heightened attention to privacy protection and participation burden, may be necessary to increase participation among less-represented groups.

Recurrent ascites and pleural effusions after surgery for early-stage endometrial adenocarcinoma.

A case of massive postoperative ascites in a woman treated for endometrial cancer is reported. A workup for typical causes of ascites yielded negative results, prompting a more detailed analysis of the patient's condition. Hypothyroidism was discovered. After correction of the hypothyroidism, the ascites slowly resolved. Since myxedema is an uncommon cause of ascites, this is usually a diagnosis of exclusion. However, hypothyroidism must be ruled out to prevent unnecessary and possibly inappropriate treatments for ascites.

New cyclooxygenase-2/5-lipoxygenase inhibitors. 3. 7-tert-butyl-2, 3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations at the 5 position.

We report an expansion of the scope of our initial discovery that 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) are antiinflammatory and analgesic agents. Several other functional groups have been introduced at the 5 position: amides, amidines, ureas, guanidines, amines, heterocycles, heteroaromatics, and heteroaryl ethenyl substituents in the 5 position all provide active compounds. These compounds are dual cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitors. They inhibit both COX-1 and COX-2 with up to 33-fold selectivity for COX-2.

MR features of developing periventricular white matter in preterm infants: evidence of glial cell migration.

PURPOSE: MR imaging of the brain is increasingly used in the investigation of the newborn, but little information is available on the normal appearance of the developing brain. We scanned a series of newborn infants in an attempt to define the normal appearance of developing periventricular white matter and to assess how pathologic conditions may modify this appearance. METHODS: Sixty-eight newborn infants, median postmenstrual age (PMA) 34 weeks (range, 24 to 42 weeks), were subdivided into two groups: group A (n = 33), which included those with normal clinical and sonographic examinations, and group B (n = 35), which contained those with evidence of neuroabnormality detected prior to the MR study, either clinically or by cerebral sonography. Images were acquired in two planes on a 1.5-T imager using turbo spin-echo pulse sequences. RESULTS: Symmetric periventricular bands of reduced signal intensity were noted in the frontal periventricular white matter on T2-weighted images in 98% of group A infants and in 97% of group B infants. The number of bands was inversely related to PMA. The reduction in number of bands with increasing PMA was delayed in group B infants. CONCLUSION: The uniform appearance of periventricular bands in a population of healthy infants and their relationship to the infants' maturity is consistent with the results of previous histologic studies. These studies demonstrate the presence of migrating glial cells within the periventricular white matter of infants beyond 20 weeks' gestation, when neuronal migration to the cortex is complete. We postulate that the bands seen on T2-weighted images represent groups of migrating glial cells, providing a further marker of cerebral maturation.

New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent.

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were prepared and evaluated as potential nonsteroidal antiinflammatory and analgesic agents. Interest in this class of compounds arose when a DHDMBF was found to be an active metabolite of the di-tert-butylphenol antiinflammatory agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs have good in vivo antiinflammatory and analgesic activity after oral administration. These compounds inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) in vitro. The cyclooxygenase inhibition was found to be selective for the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX inhibition may be responsible for the gastrointestinal safety of compounds such as 30.

Polymyalgia rheumatica is associated with both HLA-DRB1*0401 and DRB1*0404.

The frequency of HLA-DRB1 alleles was determined in 68 Caucasoid patients with polymyalgia rheumatica (PMR) and 140 controls using polymerase chain reaction (PCR) sequence-specific oligonucleotide typing. In keeping with previous studies, an increased frequency of DRB1*04 was observed in patients [55.9% vs 35.0%, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3-4.4]. HLA-DRB1*0101 frequency was also increased in patients, although less confidence could be placed on this association (19.1% vs 14.3%, OR 1.4, 95% CI 0.6-3.3). HLA-DRB1*04 subtyping indicated that the frequencies of both DRB1*0401 (38.2% vs 22.1%, OR 2.2, 95% CI 1.0-4.3) and DRB1*0404 (16.2% vs 5.0%, OR 3.7, 95% CI 1.2-11.1) were specifically raised. An increased frequency of the RA shared epitope (QKRAA/QRRAA) was also observed in this group (75.0% vs 44.2%, OR 3.8, 95% CI 1.9-7.6). When the analysis was restricted to only DRB1*04-negative patients and controls, the frequencies of DRB1*0301, *11 and *08 were marginally raised. However, no obvious relationship appeared to exist between PMR susceptibility and DRB1 alleles carrying the DYF conserved epitope in the second hypervariable region. Autoantibodies to thyroid antigens were present in 23% of patients. An increased frequency of DRB1*0301 was observed in patients with thyroid microsomal antibodies compared to those without (54.5% vs 24.6%, OR 3.7, 95% CI 0.8-17.0). This increase was not observed in patients with thyroglobulin autoantibodies. These data indicate that both DRB1*0401 and *0404 are associated with PMR, and that this may extend to include DRB1*0101. The immunogenetic profile of susceptibility markers in this condition appears to be similar to that in rheumatoid arthritis.

Milk tolerance in adults with ulcerative colitis.

OBJECTIVES: There has been concern in the literature and among physicians and patients that milk intolerance may contribute to disease activity in ulcerative colitis. We sought to define whether patients with ulcerative colitis have problems with milk tolerance. METHODS: 1) A questionnaire was administered to a group of gastroenterologists. 2) Consecutive unselected ulcerative colitis patients were administered a questionnaire regarding issues concerning their ingestion and tolerance of milk products. 3) Patients, and age- and ethnically matched controls, underwent lactose hydrogen breath testing at a 50-g dose, and if intolerant, returned for testing at a 12.5-g dose. RESULTS: Eighty percent of responding physicians stated that they recommend avoidance of milk products at some time to their patients. Thirteen of 29 (44%) ulcerative colitis patients were lactose intolerant compared with five of 14 (36%) controls (p = 0.57). Of 11 subjects returning for the 12.5-g test dose, only three (28%) were intolerant. Of 10 ulcerative colitis patients tested during a flare, only two (20%) were intolerant. Nineteen of 28 (66%) patients reduced or eliminated milk products from their diet, but only 10 (45%) of these patients were lactose intolerant. The discordance rate for predicting lactose tolerance status among patients was 35%. By logistic regression analysis, age (p = 0.04) and ethnicity (p = 0.006) were the only variables that were predictive of an abnormal lactose hydrogen breath test. CONCLUSIONS: There are common misperceptions among physicians and patients about lactose intolerance in ulcerative colitis. Lactose intolerance in patients with ulcerative colitis is dependent on their age and ethnicity and not any particular aspects of their disease. The proscription of milk products during flares of disease by many physicians is not supported by this study.

Fluorescence decay kinetics of the tryptophyl residues of myoglobin: effect of heme ligation and evidence for discrete lifetime components.

The fluorescence decay kinetics of the tryptophyl residues of sperm whale and yellowfin tuna myoglobin have been determined by using time-correlated single photon counting, with picosecond resolution. Purification by HPLC techniques resulted in the isolation of samples that exclusively displayed picosecond decay kinetics. Lifetimes of 24.4 ps for Trp14 and 122.0 ps for Trp7 were found for oxy sperm whale myoglobin (pH 7), which agree with theoretical predictions [Hochstrasser, R. M., & Negus, D. K. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 4399-4403]. The effects of ligand binding and pH on the decay kinetics were investigated, and the results were shown to be consistent with the known crystal structures. Data for the met form of sperm whale myoglobin were analyzed both in terms of a sum of discrete exponential components and as a continuous gamma distribution of exponential decays. The results were not found to support the existence of multiple, structurally distinct conformation states in myoglobin.

Resolution of heterogeneous fluorescence into component decay-associated excitation spectra. Application to subtilisins.

Direct and indirect methods are described to combine steady-state and picosecond time-resolved fluorescence decay data to generate decay-associated excitation spectra. The heterogeneous fluorescence from a fluorophore mixture that models protein fluorescence was resolved into individual component excitation spectra. The two methods were also used to determine the excitation spectra associated with each of the decay time components for the proteins subtilisin Carlsberg and BPN'. On the basis of associated spectra, the decay components of both proteins were assigned to individual (or groups of) emitting species. The two approaches used to generate the decay-associated excitation spectra are compared and their general application to protein fluorescence studies is discussed.

Characterisation of acute myocardial infarction by gated magnetic resonance imaging.

In studies with gated nuclear magnetic resonance imaging, patients with recent transmural myocardial infarction showed significantly longer spin-lattice relaxation times (T1) in the infarct area than did healthy volunteers or patients with non-ischaemic or chronic ischaemic heart disease. 10 of the 13 patients had a T1 longer than that found in any healthy subject or in any patient with other heart disease. Changes in T1 should prove useful in the assessment of interventions designed to limit infarct size.

Whole-body retention, excretion and metabolism of [74As]arsenic acid in the hamster.

In order to assess the whole-body retention, excretion and metabolism of inorganic arsenic, male and female hamsters were given either a single oral or i.v. dose of 74As (congruent to 33' microCi/hamster; 0.01 micrograms arsenic/hamster) as arsenic acid. 74As radioactivity was measured in the whole body, urine and feces for up to 35 days. 24-h samples of urine were analyzed for arsenic metabolites. For the i.v. dosed hamsters, the half-period of elimination for the first component (65% of the dose) was 0.40 days; the second component (35% of the dose) had a half-period of 4.5 days. For the orally dosed hamsters, the half-period of elimination for the first component (98% of the dose) was 0.29 days; the second component (2% of the dose) had a half-period of 3.8 days. Differences in the percent of dose excreted between oral and i.v. dosed hamsters appeared to be due to the increased fecal excretion of arsenic (70%) in the orally dosed hamsters as compared to the i.v.v dosed hamsters (6%). No statistically significant differences between the i.v. and oral treatments were found in the half-periods of elimination for either of the 2 components. Analysis of the urine for metabolites revealed arsenic was present as dimethylarsinic acid and inorganic arsenic.