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International Journal of Molecular... Jul 2022Dendritic cells (DC) and leukaemia derived DC (DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from...
Dendritic cells (DC) and leukaemia derived DC (DC) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated from mononuclear cells in vitro following standard DC/DC-generating protocols. With respect to future clinical applications though, DC/DC-generating protocols specifically designed for application in a whole-blood-(WB)-environment must be established. Therefore, we developed ten new DC/DC-generating protocols (kits; Kit-A/-C/-D/-E/-F/-G/-H/-I/-K/-M) for the generation of DC/DC from leukaemic WB, containing calcium-ionophore, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), tumour-necrosis-factor-alpha, prostaglandin-E (PGE), prostaglandin-E (PGE) and/or picibanil (OK-432). All protocols were evaluated regarding their performance in generating DC/DC using refined classification and/or ranking systems; DC/DC were evaluated regarding their performance in stimulating anti-leukaemic activity using a cytotoxicity fluorolysis assay. Overall, we found the new kits capable to generate (mature) DC/DC from leukaemic WB. Through refined classification and ranking systems, we were able to select Kit-I (GM-CSF + OK-432), -K (GM-CSF + PGE) and -M (GM-CSF + PGE) as the most efficient kits in generating (mature) DC/DC, which are further competent to stimulate immunoreactive cells to show an improved anti-leukaemic cytotoxicity as well. This great performance of Kit-I, -K and -M in mediating DC/DC-based anti-leukaemic immunity in a WB-environment in vitro constitutes an important and directive step for translating DC/DC-based immunotherapy of AML into clinical application.
Topics: Dendritic Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukemia, Myeloid, Acute; Picibanil; Prostaglandins; Prostaglandins E
PubMed: 35955486
DOI: 10.3390/ijms23158333 -
Respiratory Investigation Sep 2018Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax...
BACKGROUND
Pneumothorax occasionally develops in patients with interstitial pneumonia (IP) and is often intractable. As there exists no well-established treatment for pneumothorax with IP, we evaluated the efficacy and safety of pleurodesis with OK-432, a lyophilized preparation of Streptococcus pyogenes Su strain that has been inactivated by benzylpenicillin.
METHODS
We retrospectively evaluated the efficacy and safety of pleurodesis using OK-432 in 39 patients treated for IP-related pneumothorax between January 2006 and May 2017. Five to 10 Klinische Einheit (KE) of OK-432 was injected through the chest tube of each patient. Pleurodesis was considered successful if 1) the chest tube was removed without air leaks and 2) there was no recurrence of pneumothorax within 4 weeks after tube removal, and no additional treatment was required.
RESULTS
OK-432 pleurodesis was performed 46 times in 39 patients. The median number of OK-432 intrapleural injections received was 1 (range, 1-6), and median dose was 10 KE (range, 5-55 KE). The success rate was 63% (29/46) and recurrence rate was 17.4% (8/46). Grade 5 adverse events were observed in eight patients, including two patients who developed acute exacerbation of IP. Patients in whom the first OK-432 pleurodesis was successful had a significantly longer median survival time than patients in whom it was unsuccessful (322 days vs. 70 days, p = 0.036).
CONCLUSIONS
Our results show that OK-432 pleurodesis is an effective treatment for pneumothorax associated with IP; however, clinicians should be aware of the possibility of adverse events, especially in patients who are critically ill.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Picibanil; Pleurodesis; Pneumothorax; Retrospective Studies; Time Factors; Treatment Outcome; Young Adult
PubMed: 29903606
DOI: 10.1016/j.resinv.2018.05.003 -
Acta Oto-laryngologica May 2021Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ranula is a rare benign cystic lesion in the floor of the mouth, which can herniate through the mylohyoid muscle and become a plunging ranula. Treatment for ranulas is currently surgical excision of the sublingual gland. Sclerotherapy with OK-432 is a well-established treatment of lymphatic malformations, but not yet thoroughly evaluated on ranulas. Objectives: To evaluate sclerotherapy of ranulas with OK-432 in a randomized double-blinded trial.
MATERIALS AND METHODS
20 patients with plunging or intraoral ranula were randomized to two double-blinded injections with OK-432 or saline. Effect on the ranula and evaluation of symptoms and QOL were investigated.
RESULTS
Treatment response differed significantly between OK-432 and placebo, = .041(student's T-test). All patients with intraoral ranulas had a complete response, but only 1/4 of the patients with plunging ranula. The inflammatory reaction after injection with OK-432 caused a mild to moderate impact on QOL. No serious complications were observed.
CONCLUSION
This study suggests that sclerotherapy with OK-432 in ranula is a very effective treatment for intraoral ranulas, but possibly less useful in plunging ranulas.
SIGNIFICANCE
This is a limited study, but we believe that sclerotherapy with OK-432 should be recommended as primary treatment at least for intraoral ranulas.
Topics: Adolescent; Adult; Antineoplastic Agents; Child; Double-Blind Method; Female; Humans; Injections, Intralesional; Male; Middle Aged; Picibanil; Prospective Studies; Ranula; Sclerotherapy; Young Adult
PubMed: 33775200
DOI: 10.1080/00016489.2021.1889660 -
Cureus Sep 2022Orbital and periorbital venolymphatic malformations (VLMs) are benign congenital vascular lesions and constitute 1%-3% of all orbital masses. Widespread facial venous...
Orbital and periorbital venolymphatic malformations (VLMs) are benign congenital vascular lesions and constitute 1%-3% of all orbital masses. Widespread facial venous malformations have a high incidence of associated intracranial developmental venous anomalies (DVAs). In such cases, there can be a sudden increase in proptosis following upper respiratory infection or minor trauma. Numerous percutaneous intralesional sclerosing agents like sodium tetradecyl sulfate (STS), bleomycin, doxycycline, ethanol, and OK-432 (Picibanil) have been used for treating VLMs. We hereby report a rare case of retro-orbital VLM treated successfully with STS injection and an isolated dural arterio-venous (AV) fistula in the same patient.
PubMed: 36259024
DOI: 10.7759/cureus.29173 -
Pediatric Surgery International Dec 2022Primary spontaneous pneumothorax (PSP) commonly occurs in lean, tall, male children and adolescents. To reduce recurrence rates of PSP, chemical pleurodesis could be... (Observational Study)
Observational Study
BACKGROUND
Primary spontaneous pneumothorax (PSP) commonly occurs in lean, tall, male children and adolescents. To reduce recurrence rates of PSP, chemical pleurodesis could be helpful for patients undergoing video-assisted thoracoscopic surgery (VATS) wedge bullectomy. The efficacy and safety of intraoperative OK-432 (Picibanil) pleurodesis on preventing the recurrence of PSP in pediatric patients remain unclear.
METHODS
It is a retrospective observational study in a single center, between 2014 and 2020, enrolled 48 (8 females) pediatric PSP patients with persistent air leakage at the mean age of 16.3 ± 1.1 years to receive VATS wedge bullectomy and pleural abrasion. Twenty patients received additional intraoperative OK-432 pleurodesis. The clinical characteristics of patients, surgical outcomes, and recurrence rates were analyzed.
RESULTS
The OK-432 group had longer operation time (118.6 ± 35.6 vs. 96.5 ± 23.3 min; p < 0.05) and higher proportion of postoperative fever (75.0% vs. 28.5%; p = 0.015) than the standard group. No serious adverse events were noted and other surgical outcomes in the two groups were comparable. After a mean follow-up period of 18.1 ± 19.1 months, the OK-432 group had a lower recurrence rate compared with the standard group (5% vs. 28.6%; p < 0.05, odds ratio 0.13, 95% confidence interval: 0.01-1.15), but it had no significant difference in statistics on the Kaplan-Meier curves (log-rank p = 0.105).
CONCLUSION
It was the first study that focused on the addition of intraoperative OK-432 pleurodesis for PSP with persistent air leakage in children and adolescents receiving VATS. It demonstrated the efficacy with a low recurrence rate and short-term safety as a single-center experience.
LEVEL OF EVIDENCE
Retrospective review, therapeutic study, Level III.
Topics: Female; Humans; Male; Adolescent; Child; Pleurodesis; Pneumothorax; Picibanil; Treatment Outcome; Recurrence; Thoracic Surgery, Video-Assisted; Retrospective Studies
PubMed: 36575307
DOI: 10.1007/s00383-022-05347-0 -
International Journal of Molecular... Sep 2019Dendritic cells (DCs) and leukemia-derived DC (DC) are potent stimulators of various immunoreactive cells and they play a pivotal role in the (re-) activation of the...
Dendritic cells (DCs) and leukemia-derived DC (DC) are potent stimulators of various immunoreactive cells and they play a pivotal role in the (re-) activation of the immune system. As a potential treatment tool for patients with acute myeloid leukemia, we developed and analyzed two new PGE-containing protocols (Pici-, Kit M) to generate DC/DC ex vivo from leukemic peripheral blood mononuclear cells (PBMCs) or directly from leukemic whole blood (WB) to simulate physiological conditions. Pici- generated significantly higher amounts of DCs from leukemic and healthy PBMCs when compared to control and comparable amounts as the already established protocol Pici-. The proportions of sufficient DC-generation were even higher after DC/DC-generation with Pici-. With Kits, it was possible to generate DCs and DC directly from leukemic and healthy WB without induction of blast proliferation. The average amounts of generated DCs and DC-subgroups were comparable with all Kits. The PGE containing Kit M generated significantly higher amounts of mature DCs when compared to the PGE-containing Kit K and increased the anti-leukemic-activity. In summary PGE-containing protocols were suitable for generating DC/DC from PBMCs as well as from WB, which reliably (re-) activated immunoreactive cells, improved the overall ex vivo anti-leukemic activity, and influenced cytokine-release-profiles.
Topics: Adult; Aged; Alprostadil; Biomarkers; Cell Differentiation; Cytokines; Dendritic Cells; Female; Flow Cytometry; Humans; Immunomodulation; Immunophenotyping; Leukemia, Myeloid, Acute; Leukocytes, Mononuclear; Male; Middle Aged; Picibanil; Young Adult
PubMed: 31533251
DOI: 10.3390/ijms20184590 -
Journal of Cerebral Blood Flow and... Jun 2024Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies...
Perinatal infection or inflammation are associated with adverse neurodevelopmental effects and cardiovascular impairments in preterm infants. Most preclinical studies have examined the effects of gram-negative bacterial inflammation on the developing brain, although gram-positive bacterial infections are a major contributor to adverse outcomes. Killed Su-strain group 3 A streptococcus pyogenes (Picibanil, OK-432) is being used for pleurodesis in fetal hydrothorax/chylothorax. We therefore examined the neural and cardiovascular effects of clinically relevant intra-plural infusions of Picibanil. Chronically instrumented preterm (0.7 gestation) fetal sheep received an intra-pleural injection of low-dose (0.1 mg, n = 8) or high-dose (1 mg, n = 8) Picibanil or saline-vehicle (n = 8). Fetal brains were collected for histology one-week after injection. Picibanil exposure was associated with sustained diffuse white matter inflammation and loss of immature and mature oligodendrocytes and subcortical neurons, and associated loss of EEG power. These neural effects were not dose-dependent. Picibanil was also associated with acute changes in heart rate and attenuation of the maturational increase in mean arterial pressure. Even a single exposure to a low-dose gram-positive bacterial-mediated inflammation during the antenatal period is associated with prolonged changes in vascular and neural function.
Topics: Animals; Sheep; Female; Inflammation; Pregnancy; Brain; Streptococcus pyogenes; Fetus; Heart Rate; Neurons; Electroencephalography
PubMed: 37824725
DOI: 10.1177/0271678X231197380 -
Oral Surgery, Oral Medicine, Oral... Apr 2015The study sought to determine the optimal surgical treatment of a simple ranula and analyzed the clinical characteristics and treatment outcomes of a simple ranula in...
OBJECTIVE
The study sought to determine the optimal surgical treatment of a simple ranula and analyzed the clinical characteristics and treatment outcomes of a simple ranula in our hospital.
METHODS
A retrospective review was performed to evaluate patients with a diagnosis of a simple ranula at Chonnam National University Hwasun Hospital from November 2007 to August 2013. Clinical data on simple ranulas that were reviewed included gender, age, symptoms, duration of symptoms, location and size of lesion, surgical procedures, complications, recurrence, and follow-up.
RESULTS
The 24 patients included in the study comprised 10 males and 14 females. Sixteen patients (66.7%) did not have a prior treatment history. Eight patients had undergone previous treatment, which included Picibanil injection sclerotherapy, incision and drainage, and micromarsupialization. The simple ranula recurred after excision of the ranula and the sublingual gland in only one (4.2%) of 24 cases. In eight patients who had undergone previous treatment, there was no recurrence after excision of the ranula and sublingual gland. There were no major complications and recurrences in the patients with recurrent simple ranulas.
CONCLUSIONS
Excision of the ranula and the sublingual gland via intraoral approach is the optimal treatment for a simple ranula, even in the case of a recurrent simple ranula.
Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Male; Middle Aged; Oral Surgical Procedures; Ranula; Retreatment; Retrospective Studies; Treatment Outcome
PubMed: 25758846
DOI: 10.1016/j.oooo.2015.01.007 -
The Journal of Laryngology and Otology Dec 2015This study aimed to assess the histopathological effect of OK-432 (Picibanil) on rabbit nasal turbinates. (Comparative Study)
Comparative Study
OBJECTIVE
This study aimed to assess the histopathological effect of OK-432 (Picibanil) on rabbit nasal turbinates.
METHODS
A total of 21 rabbits were divided into 3 treatment groups and various parts of both nasal turbinates were injected with 0.5 ml OK-432, 0.2 ml OK-432 or 0.6 ml saline (control). Bilateral nasal turbinates were later excised and studied under light microscopy to assess any histopathological changes.
RESULTS
Animals in the 0.2 ml and 0.5 ml OK-432 groups exhibited mild ciliary loss, goblet cell loss and epithelial damage, and a marked increase in inflammatory cell infiltration, submucosal vascularisation and fibrosis. There was a significant difference in histopathological changes between the two OK-432 treated groups. In addition, each OK-432 treated group had significantly more inflammatory cell infiltration, increased submucosal vascularisation and fibrosis compared with controls.
CONCLUSION
The marked fibrosis observed in OK-432-injected turbinates may be responsible for a reduction in turbinate size.
Topics: Animals; Biopsy, Needle; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Immunohistochemistry; Injections, Intralesional; Male; Nasal Obstruction; Picibanil; Rabbits; Random Allocation; Sensitivity and Specificity; Turbinates
PubMed: 26456255
DOI: 10.1017/S002221511500273X -
The Medical Journal of Malaysia Oct 2019Cervico facial cystic hygroma and tongue lymphagioma is rare representative of spectrum of lymphatic malformations. Conservative management with sclerosants alone has...
Cervico facial cystic hygroma and tongue lymphagioma is rare representative of spectrum of lymphatic malformations. Conservative management with sclerosants alone has proven to be successful. However, sudden enlargement of these cervico facial lymphangiomas leads to catastrophic airway obstruction leading to debility in feeding and speech. Therefore, surgery is indicated in such case to prevent such a catastrophic problem. We report here the case of a 3-yearold boy with cervico facial hygroma involving the tongue. We successfully treated him with a combination of surgery and OK432 injection.
Topics: Antineoplastic Agents; Child, Preschool; Decision Making; Diagnosis, Differential; Glossectomy; Head and Neck Neoplasms; Humans; Injections; Lymphangioma, Cystic; Magnetic Resonance Imaging; Male; Picibanil; Therapy, Computer-Assisted; Tracheostomy
PubMed: 31649229
DOI: No ID Found