Diagnosis, treatment, and temporary remission of disseminated paecilomycosis in a vizsla

1996 ◽  
Vol 32 (6) ◽  
pp. 509-514 ◽  
Author(s):  
PA March ◽  
K Knowles ◽  
CL Dillavou ◽  
R Jakowski ◽  
G Freden
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Marked Improvement ◽  
Clinical Signs ◽  
Central Nervous System Involvement ◽  
Disease Course ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity ◽  
Multisystemic Disease

A case of disseminated paecilomycosis in a three-year-old vizsla is described. Clinical signs of lethargy, weight loss, lymphadenopathy, diarrhea, and vestibulocochlear deficits were exhibited. Dense colonization of bone marrow by the fungus was found early in the disease course. Serial culture of bone-marrow aspirates and in vitro sensitivity testing helped monitor disease progression and guide antifungal therapy. Clinical and laboratory parameters demonstrated marked improvement for a period of 12 weeks. Multisystemic disease with central nervous system involvement was found at necropsy.

Testing in Vitro Sensitivity of Minimal Residual Disease in Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2543-2543
Author(s):  
Line Groth-Pedersen ◽  
Rebecca Valentin ◽  
Kjeld Schmiegelow
Keyword(s):  
Bone Marrow ◽  
Cell Death ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Cell Populations ◽  
Sensitivity Testing ◽  
Cell Death Assay ◽  
In Vitro Sensitivity

Abstract Abstract 2543 Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease in children and adolescents. Although improved risk grouping, anti-cancer treatment, and supportive care have resulted in survival rates above 80 %, 15–20 % of patients experience a relapse, which is associated with an inferior prognosis. Relapse is caused by persistence of minimal residual disease (MRD) primarily in the bone marrow during chemotherapy, and methods for identification of drugs that are capable of eliminating the MRD cell population is necessary, but not currently available. In vitro sensitivity testing has been carried out at the time of diagnosis and shows predictive value of treatment outcome and correlation to MRD levels. However, the in vitro sensitivity profiles have not been applicable for treatment stratification, since the vast majority of leukemic cells present at diagnosis are rather chemosensitive, as opposed to the MRD population. Thus, the more sensitive clones mask the more resistant ones. We hypothesized that in vitro sensitivity testing of the more resistant MRD cells remaining in bone marrow after the induction therapy could help to stratify patients to individualized chemotherapy. The greatest challenge in carrying out in vitro sensitivity testing on MRD cell populations is the low number of leukemic cells available, i.e. 0.1–5%. Traditionally, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flourometric microculture cytotoxicity assays have been used for in vitro sensitivity testing. They, however, need several million cells for in vitro sensitivity testing of 3 drugs. We aimed at developing a cell death assay applicable on small ALL cell populations. We show that a flow cytometry based assay using annexin V (reflecting exposure of phophatidylserine on the outer cell membrane during early apoptosis) and 7-Aminoactinomycin D (reflecting cell membrane rupture during late apoptosis) staining is a reliable method for evaluating early and late stages of cell death in small ALL cell populations. Both in ALL cell lines REH (B-cell precursor (BCP) ALL, t(12;21), Jurkat (t-ALL), RS4;11 (BCP ALL, t(4;11)) and Nalm-6 (BCP ALL, t(5;12)) and in primary ALL cell samples the results are highly reproducible and show the same relative sensitivity profile as when a large number of cells are used. This cell death assay only demands a total of 20.000 cells to determine the in vitro sensitivity for 3 drugs run in triplicates at 4 concentrations. This assay is thus applicable for sorted MRD populations accounting for 0.1% of the mononuclear cells in the bone marrow. Disclosures: No relevant conflicts of interest to declare.

Functional precision medicine in colorectal cancer based on patient-derived tumoroids and in-vitro sensitivity drug testing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15567-e15567
Author(s):  
Lars Henrik Jensen ◽  
Anders Kristian Moeller Jakobsen ◽  
Birgitte Mayland Havelund ◽  
Cecilie Abildgaard ◽  
Chris Vagn-Hansen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Primary Endpoint ◽  
Drug Testing ◽  
Progression Free Survival ◽  
Patient Specific ◽  
Precision Oncology ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity

e15567 Background: Precision oncology based on in-vitro, functional assays has potential advantages compared to the much more common molecular approach, but the clinical benefit is unknown. We here report the results from the largest prospective interventional clinical trial testing the clinical outcome in colorectal cancer patients treated with drugs showing cytotoxic effect in matched patient-derived tumoroids. Methods: This single-center, phase II trial included patients with metastatic colorectal cancer previously exposed to all standard therapies. Specimens from one to three 18-16 G core needle biopsies were manually dissected, enzymatically treated, cultivated, and incubated to form 3D spherical microtumors, i.e. tumoroids. In the assay for in-vitro sensitivity testing, the tumoroids were challenged with single drugs and combinations thereof to determine patient-specific responses. Using tumoroid screening technology (IndiTreat, 2cureX, Copenhagen, Denmark), results were generated by comparing the sensitivity of the individual patient’s tumoroids with a reference panel from other patients. The testing included standard cytostatics and drugs with proven effect in previous early-phase clinical trials, a total of 15 drugs. The primary endpoint was the fraction of patients with progression-free survival (PFS) at two months. Based on placebo arms in randomized last-line trials, a minimal relevant difference of 20% (20% to 40%) was stated. Using Simon's two-stage design, a sample size of 45 patients was calculated with at least 14 PFS at two months (significance 5%, power 90%). Results: Ninety patients were enrolled from 9/2017 to 9/2020. Biopsies from 82 patients were obtained and sent for tumoroid formation of which 44 (54%, 95% CI 42-65) were successful and at least one treatment was suggested. Thirty-four patients initiated treatment according to the response obtained in the drug assays within a median of 51 days from inclusion (IQR 39-63). The primary endpoint, PFS at two months, was met in 17 of 34 patients (50%, 95%CI 32-68). There were no radiological responses. Median PFS was 81 days (95% CI 51-112) and median OS was 189 days (95% CI 103-277). Conclusions: Precision oncology using a functional approach with patient-derived tumoroids and in-vitro drug sensitivity testing seems feasible. The approach is limited by the fraction of patients with successful tumoroid development. The primary endpoint was met, as half of the patients were without progression at two months. Further clinical studies are justified. Clinical trial information: NCT03251612.

scholarly journals Relationship between Acute Suppurative Otitis Media and Chronic Secretory Otitis Media: Role of Antibiotics

1984 ◽  
Vol 77 (9) ◽  
pp. 754-757 ◽  
Author(s):  
Robert Mills ◽  
Ann Uttley ◽  
Michelle McIntyre
Keyword(s):  
Otitis Media ◽  
Middle Ear ◽  
Acute Otitis Media ◽  
Secretory Otitis Media ◽  
Sensitivity Testing ◽  
Suppurative Otitis Media ◽  
In Vitro Sensitivity ◽  
Resistance To Penicillin

A total of 204 chronic middle ear effusions from 122 children have been studied. Bacteria were isolated from 30 effusions. The commonest species found were Strep. pneumoniae and H. influenzae. These are also the commonest organisms causing acute otitis media (AOM). A similar pattern of serotypes was also demonstrated. In vitro sensitivity testing showed that most of the organisms isolated were sensitive to most commonly-used antibiotics. The main exception was resistance to penicillin amongst strains of H. influenzae and Staph. aureus. It is suggested that some cases of chronic secretory otitis media (SOM) may arise as a result of incomplete resolution of AOM and that the use of penicillin to treat AOM may be one factor in this process.

Abdominal Cryptococcosis in Two Dogs: Diagnosis and Medical Management

2015 ◽  
Vol 51 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Lindsay Tangeman ◽  
Danielle Davignon ◽  
Reema Patel ◽  
Meryl Littman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
High Risk ◽  
Amphotericin B ◽  
Medical Management ◽  
Clinical Signs ◽  
Central Nervous System Involvement ◽  
Fecal Examination ◽  
Therapy Options ◽  
Cryptococcus Spp

Canine cryptococcosis cases are typically reported as neurologic, disseminated, or both. There have been few reports of other parenchymal organ involvement. Dogs infected with Cryptococcus spp. are likely to develop central nervous system involvement, and those that are severely affected are treated aggressively with surgery and/or amphotericin B. This report describes two cases of canine abdominal cryptococcosis: one boxer with primary alimentary cryptococcosis alone and one miniature schnauzer with pancreatic and disseminated cryptococcosis. The boxer is unique in that the dog suffered from primary alimentary cryptococcosis without dissemination, secondary anemia due to gastrointestinal losses, and is the second case to have Cryptococcus spp. identified on fecal examination as part of the diagnostic workup. Unlike previous reports, surgery was not performed in either case, and both dogs were treated with fluconazole alone. Currently, both dogs are free from clinical signs, and Cryptococcus spp. antigen titers are negative at 17 and 15 mo after initial presentation. These cases suggest fluconazole may be effective therapy alone for canine abdominal cryptococcosis, negating the need for high-risk therapy options such as surgery and/or amphotericin B in some cases.

scholarly journals Efficacy of Variable Tetraconazole Rates Against Cercospora beticola Isolates with Differing In Vitro Sensitivities to DMI Fungicides

Plant Disease ◽  
2012 ◽  
Vol 96 (12) ◽  
pp. 1749-1756 ◽  
Author(s):  
Melvin D. Bolton ◽  
Viviana Rivera-Varas ◽  
Luis E. del Río Mendoza ◽  
Mohamed F. R. Khan ◽  
Gary A. Secor
Keyword(s):  
Sugar Beet ◽  
Disease Severity ◽  
Cercospora Beticola ◽  
In Planta ◽  
Sensitivity Testing ◽  
In Vitro Sensitivity ◽  
Wide Range ◽  
Fungicide Efficacy ◽  
Dmi Fungicides

Cercospora leaf spot (CLS) of sugar beet is caused by the fungus Cercospora beticola. CLS management practices include the application of the sterol demethylation inhibitor (DMI) fungicides tetraconazole, difenoconazole, and prothioconazole. Evaluating resistance to DMIs is a major focus for CLS fungicide resistance management. Isolates were collected in 1997 and 1998 (baseline sensitivity to tetraconazole, prothioconazole, or difenoconazole) and 2007 through 2010 from the major sugar-beet-growing regions of Minnesota and North Dakota and assessed for in vitro sensitivity to two or three DMI fungicides. Most (47%) isolates collected in 1997–98 exhibited 50% effective concentration (EC50) values for tetraconazole of <0.01 μg ml–1, whereas no isolates could be found in this EC50 range in 2010. Since 2007, annual median and mean tetraconazole EC50 values have generally been increasing, and the frequency of isolates with EC50 values >0.11 μg ml–1 increased from 2008 to 2010. In contrast, the frequency of isolates with EC50 values for prothioconazole of >1.0 μg ml–1 has been decreasing since 2007. Annual median difenoconazole EC50 values appears to be stable, although annual mean EC50 values generally have been increasing for this fungicide. Although EC50 values are important for gauging fungicide sensitivity trends, a rigorous comparison of the relationship between in vitro EC50 values and loss of fungicide efficacy in planta has not been conducted for C. beticola. To explore this, 12 isolates exhibiting a wide range of tetraconazole EC50 values were inoculated to sugar beet but no tetraconazole was applied. No relationship was found between isolate EC50 value and disease severity. To assess whether EC50 values are related to fungicide efficacy in planta, sugar beet plants were sprayed with various dilutions of Eminent, the commercial formulation of tetraconazole, and subsequently inoculated with isolates that exhibited very low, medium, or high tetraconazole EC50 values. The high EC50 isolate caused significantly more disease than isolates with medium or very low EC50 values at the field application rate and most reduced rates. Because in vitro sensitivity testing is typically carried out with the active ingredient of the commercial fungicide, we investigated whether loss of disease control was the same for tetraconazole as for the commercial product Eminent. The high EC50 isolate caused more disease on plants treated with tetraconazole than Eminent but disease severity was not different between plants inoculated with the very low EC50 isolate.

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