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Cureus Jun 2022Sarcoidosis is a multisystem inflammatory chronic disorder that can virtually affect any organ system in the body. Most commonly affected organs are the intrathoracic...
Sarcoidosis is a multisystem inflammatory chronic disorder that can virtually affect any organ system in the body. Most commonly affected organs are the intrathoracic structures with 90% of the reported cases involving the lungs. Esophageal involvement in sarcoidosis is extremely rare. Involvement of the esophagus and kidney along with hematological involvement is extremely uncommon in the same patient. Here, we present a case of a 58-year-old gentleman with a similar rare presentation. The patient presented with shortness of breath, productive cough, fatigue, and difficulty in swallowing, along with a weight loss of 20-30 pounds over three months. Laboratory workup was significant for leukopenia (2900 K/UL), serum creatinine level of 2.7 mg/dL (baseline: 1.2-1.7), and raised angiotensin-converting enzyme level at 187 nmol/ml/min. Chest X-ray showed bilateral widespread fine reticulonodular opacities, chest CT showed extensive bilateral reticulonodular opacities throughout the lung parenchyma, and fine-needle aspiration cytology of the right lung showed noncaseating granulomas. No fungal or acid-fast organisms were identified, and no evidence of malignancy was seen. Special stains for fungal (Grocott's methenamine silver and periodic acid-Schiff) and acid-fast organisms (acid-fast bacilli (AFB) and fluorescent AFB) were negative. Esophagogastroduodenoscopy (EGD) with gastric biopsy showed acute and chronic inflammation and no intestinal metaplasia, dysplasia, or malignancy was identified. Bronchoalveolar lavage was done, which showed macrophages (74%), neutrophils (6%), eosinophils (3%), and lymphocytes (17%), and was negative for malignant cells. QuantiFERON and AFB sputum/ polymerase chain reaction were negative. The patient was initially started on intravenous fluids and calcitonin, which significantly improved renal function and the calcium status of the body. Then prednisone 40 mg daily was started, which improved swallowing and breathing. After a week, prednisone was changed to 20 mg daily and was continued at the time of discharge.
PubMed: 35785011
DOI: 10.7759/cureus.25600 -
Annals of Palliative Medicine May 2020Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. Cryptococcus is the opportunistic...
BACKGROUND
Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. Cryptococcus is the opportunistic pathogen. Immune damage and chronic consumptive diseases are the high risk. The prevalence of cryptococcus infection is 5% to 10% in individuals with weakened immune function. In recent years, with the application of glucocorticoids, antitumor drugs, and broad-spectrum antibiotics, the prevalence of cryptococcal infection has increased yearly. Cryptococcus infection can also occur in normal people without underlying diseases. One in every 100,000 individuals with normal immune function is also affected, but these cases are often misdiagnosed due to inadequate understanding and low awareness of PC in individuals with normal immune function. In this study, we investigated the clinical characteristics of PC in patients with normal immune function to improve the diagnosis and treatment of these cases.
METHODS
We retrospectively analyzed the clinical, imaging and pathological data of 16 patients with pulmonary cryptococcosis treated at Beijing Shijitan Hospital between 2010 and 2017.
RESULTS
Of the 16 patients with disseminated cryptococcosis, 6 were men, and 10 were women; their ages were 35 to 76 years (median: 53 years). Initial symptoms were cough, sputum, chest pain, and fever. Thirteen patients had a history of chronic disease or tumor, including diabetes and bronchial asthma (n=2), simple hypertension (n=2), chronic bronchitis (n=2), diabetes and hypertension (n=5), previous tuberculosis (n=1), and previous lung cancer surgery (n=1). Chest computed tomography (CT) in these 16 patients showed single or multiple nodules and masses (n=14), lobar consolidation (n=1), and diffuse mixed lesions (n =1). Lung biopsy showed granulomatous lesions in these 16 patients. Cryptococcus neoformans was identified with Grocott's methenamine silver and Grocott's methenamine silver (GMS) stains. Fourteen patients received fluconazole alone; two patients with intracranial infection received fluconazole combined with amphotericin B. Five patients improved significantly, and nine patients improved with significant lesion absorption.
CONCLUSIONS
The clinical manifestations of PC are nonspecific in patients with normal immune function. Lung biopsy and cryptococcus antigen tests of cerebrospinal fluid are valuable diagnostic aids. Fluconazole is an effective treatment for disseminated cryptococcal infection.
Topics: Adult; Aged; Cryptococcosis; Cryptococcus neoformans; Female; Humans; Immunity; Lung Diseases, Fungal; Male; Middle Aged; Retrospective Studies
PubMed: 32434369
DOI: 10.21037/apm-20-897 -
Journal of Medicinal Chemistry Dec 2021Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved...
Commonly used non-antibiotic drugs have been associated with changes in gut microbiome composition, paving the way for the possibility of repurposing FDA-approved molecules as next-generation microbiome therapeutics. Herein, we developed and validated an high-throughput screening platform─the mini gut model─to underpin human gut microbiome response to molecular modulators. Ten FDA-approved compounds, selected based on maximum structural diversity of molecular fingerprints, were screened against the gut microbiome of five healthy subjects to characterize the ability of human-targeted drugs to modulate the human gut microbiome network. Three compounds, THIP hydrochloride, methenamine, and mesna, have shown promise as novel gut microbiome therapeutics in light of their capability of promoting health-associated features of the gut microbiome. Our findings provide a resource for future research on drug-microbiome interactions and lay the foundation for a new era of more precise gut microbiome modulation through drug repurposing, aimed at targeting specific dysbiotic events.
Topics: Drug Repositioning; Gastrointestinal Microbiome; Gene Expression Profiling; High-Throughput Screening Assays; Humans; Validation Studies as Topic
PubMed: 34846885
DOI: 10.1021/acs.jmedchem.1c01333 -
The British Journal of General Practice... Jul 2021Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Urinary tract infections (UTIs) are often treated with antibiotics and are a source of antibiotic overuse.
AIM
To systematically review randomised controlled trials (RCTs) of adult women in the community with a history of recurrent UTIs and who use methenamine hippurate prophylactically.
DESIGN AND SETTING
Systematic review of women in the UK, Australia, Norway, and US (aged ≥18 years) with recurrent UTIs receiving methenamine hippurate against placebo or no treatment, and antibiotics.
METHOD
The authors searched three databases, clinical trial registries, and performed forward-backward citation analysis on references of included studies.
RESULTS
Six studies involving 557 participants were included (447 were analysed). Of the six studies, five were published and one was an unpublished trial record with results, three compared methenamine hippurate against placebo or control, and three compared methenamine hippurate with antibiotics. For the number of patients who remained asymptomatic, methenamine hippurate showed a non-statistically significant trend of benefit versus antibiotics over 12 months (risk ratio [RR] 0.65, 95% confidence interval [CI] = 0.40 to 1.07, 49%), versus control over 6 or 12 months (RR 0.56, 95% CI = 0.13 to 2.35, 93%), and a non-statistically significant trend versus any antibiotic for abacteruria (RR 0.80, 95% CI = 0.62 to 1.03, 23%). A similar non-statistically significant trend of benefits for methenamine hippurate for the number of UTI or bacteriuric episodes was found, and a non-statistically significant difference in the number of patients experiencing adverse events between methenamine hippurate and any comparator, with a trend towards benefit for the methenamine hippurate, was identified. Antibiotic use and resistance were not consistently reported.
CONCLUSION
There is insufficient evidence to be certain of the benefits of methenamine hippurate to prevent UTI. Further research is needed to test the drug's effectiveness in preventing UTIs and as an alternative for antibiotic treatment for UTI.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Female; Hippurates; Humans; Methenamine; Pharmaceutical Preparations; Urinary Tract Infections
PubMed: 34001538
DOI: 10.3399/BJGP.2020.0833 -
Journal of Laboratory Physicians Jun 2023Histoplasmosis is an infectious disease caused by the dimorphic fungus . Histoplasmosis is considered to be endemic to India, especially the Gangetic belt....
Histoplasmosis is an infectious disease caused by the dimorphic fungus . Histoplasmosis is considered to be endemic to India, especially the Gangetic belt. Disseminated histoplasmosis may affect almost all systems. Disseminated histoplasmosis with asymptomatic adrenal involvement has been described in immunocompromised patients, whereas isolated adrenal involvement as the presenting manifestation in immunocompetent is uncommon. We aimed to determine the clinicopathological and radiological findings of adrenal histoplasmosis in immunocompetent patients attending a multispecialty diagnostic center referred from different clinics and hospitals. All tissue samples were initially examined microscopically by performing potassium hydroxide (KOH) wet mounts, followed by culture on two tubes of Sabouraud dextrose agar and phase conversion. Histopathological correlation was done using tissue stains, hematoxylin and eosin, periodic acid-Schiff, and Gomori methenamine silver. We evaluated 84 clinically suspected cases radiologically for adrenal mass. The pathological and microbiological work-up was done from these suspected cases. A total of 19 cases were evident from the tissue stain and fungal culture methods. The affected population were mostly above 45 years and male. Seven patients had bilateral adrenal involvement. All these patients received amphotericin B and/or itraconazole treatment, which led to symptomatic improvement in most cases. Diagnosis of invasive fungal infection requires a high index of suspicion, especially in immunocompetent patients presenting with nonspecific symptoms, clinical signs, and laboratory and radiological features that often resemble adrenal neoplasms. Clinical specimens, together with fungal culture, must be sent for cytopathology/histopathology for a definite diagnosis and appropriate management.
PubMed: 37323606
DOI: 10.1055/s-0042-1757587 -
BMC Nephrology Jun 2023Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis...
BACKGROUND
Light and heavy chain deposition disease (LHCDD) is a rare condition characterised by the deposition of immunoglobulin components in the kidneys. Similarly, Amyloidosis is also caused by the deposition of light chain and/or heavy chain components of immunoglobulins which are folded into amyloid fibrils characterised by Congophilic deposits that exhibit apple-green birefringence under polarised light. Only a handful of reports describing LHCDD with amyloid fibril deposition have been previously published, however, none have characterized the composition of the deposited immunoglobulin components via mass spectrometry.
CASE PRESENTATION
We report a case of a 79-year-old Japanese woman with nephrotic syndrome. Bone marrow aspiration revealed a slight proliferation of plasma cells (under 10%). Immunofluorescence assessment of renal biopsy showed amyloid-like deposits in the glomerulus that were positive for IgA and kappa. Further, the Congo red staining of the deposits was faintly positive, and only a slight birefringence was detected. Electron microscopy confirmed fine fibrillar structures and non-amyloid deposits. Finally, mass spectrometry revealed that the deposits were composed of abundant amounts of light chain with small amounts of heavy chain. Therefore, the patient was diagnosed with LHCDD and focal amyloid deposition. Chemotherapy was subsequently initiated, which resulted in haematological and renal response. Under polarised light, faint birefringence with Congo red staining and periodic acid-methenamine silver positivity indicated that the deposits were mostly non-amyloid fibrils with a small component of amyloid fibrils. Generally, the diagnosis of heavy- and light-chain amyloidosis is defined by greater heavy chain deposition compared to the light chain. However, in our case, contrary to the definition, the light-chain deposition was far greater than that of the heavy-chain.
CONCLUSIONS
This is the first case of LHCDD with focal amyloid deposition diagnosed by analysing the glomerular deposits by mass spectrometry.
Topics: Female; Humans; Aged; Congo Red; Amyloidosis; Immunoglobulins; Multiple Myeloma; Amyloid; Mass Spectrometry; Immunoglobulin Light Chains
PubMed: 37365566
DOI: 10.1186/s12882-023-03207-0 -
Indian Journal of Pathology &... Apr 2024Cryptococcosis usually occurs in immunocompromised patients and presents as meningitis and lung disease. Adrenal gland involvement may be observed, yet primary adrenal...
Cryptococcosis usually occurs in immunocompromised patients and presents as meningitis and lung disease. Adrenal gland involvement may be observed, yet primary adrenal insufficiency by cryptococcal infection is infrequent. We present a case of a middle-aged immunocompetent man with primary adrenal insufficiency and bilateral adrenal lesions, splenomegaly, and miliary mottling in the lungs on imaging. No evidence of meningitis was witnessed. The clinico-radiological findings led toward the differential diagnosis of disseminated tuberculosis or fungal infection. Detection of cryptococcus organism was done on fine-needle aspiration cytology and biopsy on periodic acid-Schiff stain and Gomori`s methenamine silver stain. Thus, it is recommended to keep the possibility of cryptococcosis in mind while dealing with instances that have a tuberculosis-like clinico-radiological presentation. The detection of the causal organism on Fine needle aspiration (FNA)/biopsy examination may be useful in confirming the diagnosis and determining the appropriate medical treatment.
Topics: Humans; Male; Cryptococcosis; Biopsy, Fine-Needle; Adrenal Insufficiency; Middle Aged; Adrenal Glands; Cryptococcus; Diagnosis, Differential; Tomography, X-Ray Computed; Lung; Microscopy; Adrenal Gland Diseases; Immunocompetence; Histocytochemistry
PubMed: 38391340
DOI: 10.4103/ijpm.ijpm_185_22 -
Drugs - Real World Outcomes Dec 2022Inappropriate antimicrobial use can lead to adverse consequences, including antimicrobial resistance. The objective of our study was to describe patterns of prophylactic...
BACKGROUND AND OBJECTIVE
Inappropriate antimicrobial use can lead to adverse consequences, including antimicrobial resistance. The objective of our study was to describe patterns of prophylactic antimicrobial prescribing in Australian residential aged-care facilities and thereby provide insight into antimicrobial stewardship strategies that might be required.
METHODS
Annual point prevalence data submitted by participating residential aged-care facilities as part of the Aged Care National Antimicrobial Prescribing Survey between 2016 and 2020 were extracted. All antimicrobials except anti-virals were counted; methenamine hippurate was classified as an antibacterial agent.
RESULTS
The overall prevalence of residents prescribed one or more prophylactic antimicrobial on the survey day was 3.7% (n = 4643, 95% confidence interval 3.6-3.8). Of all prescribed antimicrobials (n = 15,831), 27.1% (n = 4871) were for prophylactic use. Of these prophylactic antimicrobials, 87.8% were anti-bacterials and 11.4% antifungals; most frequently, cefalexin (28.7%), methenamine hippurate (20.1%) and clotrimazole (8.8%). When compared with prescribing of all antimicrobial agents, prophylactic antimicrobials were less commonly prescribed for pro re nata administration (7.0% vs 20.3%) and more commonly prescribed greater than 6 months (52.9% vs 34.1%). The indication and review or stop date was less frequently documented (67.5% vs 73.8% and 20.9% vs 40.7%, respectively). The most common body system for which a prophylactic antimicrobial was prescribed was the urinary tract (54.3%). Of all urinary tract indications (n = 2575), about two thirds (n = 1681, 65.3%) were for cystitis and 10.6% were for asymptomatic bacteriuria.
CONCLUSIONS
Our results clearly identified immediate antimicrobial stewardship strategies that aim to improve prophylactic antimicrobial prescribing in Australian residential-aged care facilities are required.
PubMed: 35962922
DOI: 10.1007/s40801-022-00323-5 -
Journal of Animal Science and... Feb 2021Due to the high prevalence and complex etiology, bovine mastitis (BM) is one of the most important diseases to compromise dairy cow health and milk quality. The shift in...
BACKGROUND
Due to the high prevalence and complex etiology, bovine mastitis (BM) is one of the most important diseases to compromise dairy cow health and milk quality. The shift in milk compositions has been widely investigated during mastitis, but recent studies suggested that gastrointestinal microorganism also has a crucial effect on the inflammation of other peripheral tissues and organs, including the mammary gland. However, research focused on the variation of rumen inner-environment during mastitis is still limited. Therefore, the ruminal microbial profiles, metabolites, and milk compositions in cows with different udder health conditions were compared in the present study. Furthermore, the correlations between udder health status and ruminal conditions were investigated. Based on the somatic cell counts (SCC), California mastitis test (CMT) parameters and clinical symptoms of mastitis, 60 lactating Holstein dairy cows with similar body conditions (excepted for the udder health condition) were randomly divided into 3 groups (n = 20 per group) including the healthy (H) group, the subclinical mastitis (SM) group and the clinical mastitis (CM) group. Lactation performance and rumen fermentation parameters were recorded. And rumen microbiota and metabolites were also analyzed via 16S rRNA amplicon sequencing and untargeted metabolomics, respectively.
RESULTS
As the degree of mastitis increased, rumen lactic acid (LA) (P < 0.01), acetate, propionate, butyrate, valerate (P < 0.001), and total volatile fatty acids (TVFAs) (P < 0.01) concentrations were significantly decreased. In the rumen of CM cows, the significantly increased bacteria related to intestinal and oral inflammation, such as Lachnospiraceae (FDR-adjusted P = 0.039), Moraxella (FDR-adjusted P = 0.011) and Neisseriaceae (FDR-adjusted P = 0.036), etc., were accompanied by a significant increase in 12-oxo-20-dihydroxy-leukotriene B4 (FDR-adjusted P = 5.97 × 10) and 10beta-hydroxy-6beta-isobutyrylfuranoeremophilane (FDR-adjusted P = 3.88 × 10). Meanwhile, in the rumen of SM cows, the Ruminiclostridium_9 (FDR-adjusted P = 0.042) and Enterorhabdus (FDR-adjusted P = 0.043) were increased along with increasing methenamine (FDR-adjusted P = 6.95 × 10), 5-hydroxymethyl-2-furancarboxaldehyde (5-HMF) (FDR-adjusted P = 2.02 × 10) and 6-methoxymellein (FDR-adjusted P = 2.57 × 10). The short-chain fatty acids (SCFAs)-producing bacteria and probiotics in rumen, including Prevoterotoella_1 (FDR-adjusted P = 0.045) and Bifidobacterium (FDR-adjusted P = 0.035), etc., were significantly reduced, with decreasing 2-phenylbutyric acid (2-PBA) (FDR-adjusted P = 4.37 × 10).
CONCLUSION
The results indicated that there was a significant shift in the ruminal microflora and metabolites associated with inflammation and immune responses during CM. Moreover, in the rumen of cows affected by SM, the relative abundance of several opportunistic pathogens and the level of metabolites which could produce antibacterial compounds or had a competitive inhibitory effect were all increased.
PubMed: 33557959
DOI: 10.1186/s40104-020-00543-1 -
Veterinary World Mar 2020Kidney regeneration is required for dogs with end-stage renal failure. Decellularization is one of the bioengineering techniques, which involves the removal of all...
BACKGROUND AND AIM
Kidney regeneration is required for dogs with end-stage renal failure. Decellularization is one of the bioengineering techniques, which involves the removal of all tissue cells and cellular components and conservation of the extracellular matrix (ECM). Studies in rats have shown that decellularized kidney has regenerative potential; however, there are no reports on renal decellularization in dogs. Here, we showed the decellularization of the canine kidney.
MATERIALS AND METHODS
The renal artery of the cadaveric canine kidney was cannulated and the whole kidney was frozen at -80°C. After completely thawing, it was perfused with physiological saline and sodium dodecyl sulfate (0.5%, 6 h) through the cannulated renal artery to achieve decellularization. To assess the efficiency of the decellularization protocol, histological and immunohistochemical analysis of decellularized kidney was performed.
RESULTS
The results of hematoxylin and eosin (H and E) staining revealed that the decellularized canine kidney had no apparent cellular components. In addition, 4',6-diamidino-2-phenylindole (DAPI) staining showed no visible nuclear components within the whole decellularized kidney. Therefore, both H and E and DAPI staining showed decellularization of the canine kidney. Our decellularization protocol also preserved the basement membrane of glomerulus, shown by periodic acid methenamine silver, periodic acid-Schiff, fibronectin, and collagen type IV stain.
CONCLUSION
Our decellularization protocol could eliminate cellular components and remaining native ECM structures of canine kidney. These results could promote further research into canine kidney regeneration, which may be the first small step to regenerate the canine kidney waiting for renal transplantation.
PubMed: 32367949
DOI: 10.14202/vetworld.2020.452-457