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BMJ Case Reports Jun 2024A white Caucasian woman in her 30s presented with an indurated lesion on her right upper arm. Panniculitis was clinically suspected. Antinuclear antibody testing was...
A white Caucasian woman in her 30s presented with an indurated lesion on her right upper arm. Panniculitis was clinically suspected. Antinuclear antibody testing was positive but incisional biopsy showed subcutaneous panniculitis-like T-cell lymphoma (SPTCL), although with some unusual features more in keeping with lupus. Initial treatment was with oral prednisolone and radiotherapy but with only partial response. A second biopsy was taken from an area of presumed residual disease. This displayed histological features that were much more typical of lupus erythematosus profundus (LEP) but with tiny foci suggesting concomitant microscopic areas of SPTCL. Immunofluorescence for IgM was positive. This case highlights the rare occurrence of a patient with overlapping clinical and pathological features of SCPTL and LEP. It emphasises the need for close clinicopathological correlation in the workup of patients with suspected panniculitis and the importance of careful pathological examination for features of both diseases.
Topics: Humans; Female; Panniculitis; Panniculitis, Lupus Erythematosus; Lymphoma, T-Cell; Adult; Diagnosis, Differential; Biopsy; Prednisolone
PubMed: 38925673
DOI: 10.1136/bcr-2023-255592 -
Reproduction in Domestic Animals =... Jun 2024Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The...
Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.
Topics: Animals; Female; Ki-67 Antigen; Dogs; Apoptosis; Mammary Glands, Animal; Caspase 3; Cell Proliferation; Estrous Cycle; Progesterone; Estradiol; Epithelial Cells
PubMed: 38924202
DOI: 10.1111/rda.14655 -
American Journal of Reproductive... Jun 2024
Authors' reply: Commentary on "Intrauterine perfusion of dexamethasone improves pregnancy outcomes in recurrent reproductive failure patients with elevated uterine natural killer cells. A retrospective cohort study".
Topics: Humans; Female; Pregnancy; Dexamethasone; Killer Cells, Natural; Uterus; Pregnancy Outcome; Retrospective Studies; Perfusion; Abortion, Habitual
PubMed: 38923191
DOI: 10.1111/aji.13866 -
Reproduction in Domestic Animals =... Jun 2024Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high...
Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high dropout rate of reared bulls is a problem for AI centres. Potential hormonal indicators of bull sexual maturation (cortisol, dehydroepiandrosterone (DHEA), testosterone, oestradiol, insulin-like growth factor 1 (IGF-1)) were observed and evaluated in relation to the performance parameters to perhaps identify candidate biomarkers allowing an early selection of bulls as suitable sires. Blood samples from 102 German Holstein calves at 4 ± 1, 8 ± 1 and 12 ± 2 months of age from six AI centres were analysed using validated immunoassays for cortisol, DHEA, testosterone, oestradiol and IGF-1. Semen analyses included native and thawed diluted semen. Bulls were classified at the first semen collection into groups with good versus poor performance (GP vs. LP). After 2 years, the subsequent differentiation was done in high (HPP), medium (MPP) and low performance persistency (LPP). Age at first semen collection was an important factor for sperm quality. Cortisol concentrations decreased with age, but the cortisol/DHEA ratio decreased with age only in GP bulls (p < .05). Oestradiol and testosterone concentrations both correlated with libido behaviour (p < .05). Testosterone and IGF-1 concentrations were higher at the time of first semen collection in GP bulls and increased with age (p < .05). In conclusion, testosterone and IGF-1 concentrations at first semen collection are associated with performance at first semen collection and future performance persistency, and might be useful early biomarkers for consistent sperm producing bulls on AI centres.
Topics: Animals; Male; Cattle; Insemination, Artificial; Biomarkers; Semen Analysis; Estradiol; Testosterone; Insulin-Like Growth Factor I; Hydrocortisone; Sexual Maturation; Semen; Dehydroepiandrosterone
PubMed: 38923114
DOI: 10.1111/rda.14646 -
Reproduction in Domestic Animals =... Jun 2024The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the...
The cervix is an important organ that has to dilate sufficiently at delivery to allow the foetus to transition to extrauterine life. Insufficient dilatation of the cervix (IDC) is a frequent cause of dystocia in cattle. The mechanisms underlying cervical opening and the pathogenesis of IDC are still widely unclear. Systematic studies on the relationship between IDC and steroid hormones have been limited and have yielded inconsistent findings. This study aimed to measure oestrogen and progesterone (P4) concentrations in intrapartum cows presented with dystocia due to IDC and in a comparison (C) group of cows with eutocic delivery. Before any obstetrical procedures, and right after the initial evaluation, blood samples were taken from IDC and C animals. Concentrations of P4, oestradiol-17β (E2), free total oestrogens (FTE) and conjugated total oestrogens (CTE) were measured by established radioimmunoassays. Concentrations of P4 (p = .538), FTE (p = .065) and CTE (p = .605) were not statistically different between C and IDC groups. However, E2 levels in group C were significantly lower when compared to those in the IDC group (p = .013), which is inconsistent with the function of oestrogens in cervical dilatation. The correlation analysis demonstrated significant positive correlations between the pairs P4 versus FTE, P4 versus E2 and FTE versus E2 in group C and between the pair FTE versus E2 in group IDC. In conclusion, the results suggest that local activities of steroids relevant to the aetiology of IDC are not reflected by concentrations in the systemic circulation or that other factors are clearly more important.
Topics: Animals; Female; Cattle; Progesterone; Pregnancy; Cervix Uteri; Estrogens; Dystocia; Estradiol; Cattle Diseases
PubMed: 38923054
DOI: 10.1111/rda.14656 -
Annals of the Academy of Medicine,... Nov 2023AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical... (Review)
Review
AL amyloidosis is the most common form of systemic amyloidosis. However, the non-specific nature of presenting symptoms requires the need for a heightened clinical suspicion to detect unexplained manifestations in the appropriate clinical setting. Early detection and treatment are crucial as the degree of cardiac involvement emerges as a primary prognostic predictor of survival in a patient with AL amyloidosis. Following the diagnosis of AL amyloidosis with appropriate tissue biopsies, prompt treatment with a bortezomib, cyclophosphamide and dexamethasone-based first-line induction with or without daratumumab should be initiated. The goal of treatment is to achieve the best haematologic response possible, ideally with involved free light chain <20 mg/L, as it offers the best chance of organ function improvement. Treatment should be changed if patients do not achieve a partial response within 2 cycles of treatment or very good partial response after 4 cycles or after autologous stem cell transplant, as achievement of profound and prolonged clonal responses translates to better organ response and long-term outcomes. Early involvement of multidisciplinary subspecialists such as renal physicians, cardiologists, neurologists, and gastroenterologists for optimal maintenance and support of involved organs is recommended for optimal management of patients with AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Dexamethasone; Singapore; Bortezomib; Cyclophosphamide; Antineoplastic Combined Chemotherapy Protocols; Consensus; Antibodies, Monoclonal; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation
PubMed: 38920149
DOI: 10.47102/annals-acadmedsg.2023101 -
Military Medicine Jun 2024The U.S. Marine Corps (USMC) recruit training is a 13-week preparatory period for military service men and women. Differences in absolute performance capabilities...
INTRODUCTION
The U.S. Marine Corps (USMC) recruit training is a 13-week preparatory period for military service men and women. Differences in absolute performance capabilities between sexes may impact physical and physiological responses to the demands of recruit training. The purpose of this study was to monitor U.S. Marine Corps recruits throughout recruit training to comparatively assess workload, sleep, stress, and performance responses in men and women.
MATERIALS AND METHODS
A total of 281 recruits (men = 182 and women = 99; age = 19 ± 2 years) were monitored and tested. Workload, sleep, and stress assessments occurred at week 2, week 7/8, and week 11 of training. Workload (energy expenditure per kg body mass [EEREL], distance [DIS], steps) and sleep (continuity and duration) were tracked over 72-hour periods using wearable accelerometry and heart rate technology. Stress responses were determined through salivary cortisol analyses. Performance testing, consisting of countermovement vertical jump (CMJ) and isometric mid-thigh pull (IMTP) performance relative to body mass, occurred at weeks 2 and 11. Linear mixed models were used to test for sex, time, and sex-by-time interactions (α < .05).
RESULTS
On average, recruits covered 13.0 ± 2.7 km/day, expended 3,762 ± 765 calories/day, and slept 6.2 ± 1.1 hours/night. Sex-by-time interactions were found for DIS, steps, sleep duration, cortisol, and CMJREL performance (P < .05). Planned contrasts revealed that men covered more DIS than women at week 7/8 (P < .001). Women experienced greater step counts compared to men at week 11 (P = .004). Women experienced no significant change in sleep duration (P > .05), whereas men increased sleep duration from week 2 to week 7/8 (P = .03). Women experienced greater sleep duration at week 2 (P = .03) and week 11 (P = .02) compared to men. Women exhibited higher cortisol levels than men at week 2 (P < .001) and week 11 (P < .001). Women experienced declines in cortisol at week 7 compared to week 2 (P < .001). Men experienced no changes in cortisol response at any timepoint (P > .05). Both sexes experienced declines in CMJREL from week 2 to week 11 (P > .001). Sex main effects were observed for EEREL, DIS, CMJREL, and IMTPREL (P < .05) with men experiencing greater overall workloads and producing greater strength and power metrics. Sex main effects were also found for sleep continuity and cortisol (P < .05), for which men experienced lower values compared to women. Time main effects were observed for EEREL, DIS, steps, cortisol, CMJREL, and IMTPREL (P < .05).
CONCLUSIONS
This study not only highlights the known sex differences between men and women but also sheds light on the different physical and physiological responses of each sex to military training. Interestingly, the greatest physical demands incurred earlier in the training cycle. Despite declining workloads, the stress response was maintained throughout the training, which may have implications for adaptation and performance. In addition, average sleep duration fell notably below recommendations for optimizing health and recovery. Effectively monitoring the demands and performance outcomes during recruit training is essential for determining individual fitness capabilities, as well as establishing the effectiveness of a training program. Individual performance assessments and adequately periodized workloads may help to optimize recruit training for both men and women.
Topics: Humans; Male; Female; Military Personnel; United States; Young Adult; Sex Factors; Adolescent; Hydrocortisone; Sleep; Accelerometry; Energy Metabolism; Workload; Adult
PubMed: 38920031
DOI: 10.1093/milmed/usae071 -
AAPS PharmSciTech Jun 2024The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances...
The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity.
Topics: Micelles; Dexamethasone; Chitosan; Gels; Drug Delivery Systems; Poloxamer; Drug Liberation; Surface-Active Agents; Chemistry, Pharmaceutical; Hydrogels; Anti-Inflammatory Agents; Nanoparticles; Drug Carriers; Rheology; Oral Ulcer; Administration, Oral; Lipids; Oleic Acid
PubMed: 38918282
DOI: 10.1208/s12249-024-02862-2 -
Transplant International : Official... 2024In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and... (Observational Study)
Observational Study
In this longitudinal observational study, we measured urinary glucose concentration, body composition and volume status (bioimpedance spectroscopy) and plasma renin and aldosterone concentrations in = 22 kidney transplant recipients (KTRs) initiating on SGLT2I at baseline (BL), and after 1 week and 1, 3, and 6 months. Estimated glomerular filtration rate (eGFR) decreased by -2 mL/min/1.73 m (IQR -10-0) after 1 week and remained stable thereafter. Urinary glucose concentration was 10 (3-24) g/g creatinine after 1 week and correlated with eGFR (r = 0.273; = 0.057). SGLT2I did not affect HbA1c, fasting blood glucose, body weight, fat or lean mass. SGLT2I decreased fluid overload dependent on baseline overhydration (OH, r = 0.54, = 0.0003) without occurrence of dehydration. Plasma aldosterone increased at day 7, while plasma renin did not change significantly. In conclusion, SGLT2I corrected fluid overload in patients with elevated overhydration at baseline, while in euvolemic KTRs fluid status remained stable without reduction of body water below the reference range, thus promoting the safety of SGLT2I therapy in patients following kidney transplantation. Glucosuria, together with effects of SGLT2I on blood glucose control and body weight, is attenuated in KTRs dependent on eGFR.
Topics: Humans; Kidney Transplantation; Male; Female; Middle Aged; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Glomerular Filtration Rate; Longitudinal Studies; Adult; Aldosterone; Aged; Renin; Water-Electrolyte Imbalance; Body Composition; Blood Glucose; Transplant Recipients
PubMed: 38915756
DOI: 10.3389/ti.2024.12879 -
Frontiers in Immunology 2024With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in...
With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.
Topics: Humans; Female; Aged; Adrenal Insufficiency; Immune Checkpoint Inhibitors; Addison Disease; Hydrocortisone
PubMed: 38915406
DOI: 10.3389/fimmu.2024.1371527