scholarly journals THE THERAPEUTIC VALUE OF INTRAMUSCULAR DOSAGE OF TYPE I PNEUMOCOCCUS ANTISERA

1932 ◽  
Vol 55 (6) ◽  
pp. 925-937 ◽  
Author(s):  
Theodore J. Curphey ◽  
Herman B. Baruch
Keyword(s):  
Clinical Trial ◽  
Blood Stream ◽  
Bactericidal Effect ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Human Beings ◽  
Lobar Pneumonia ◽  
Therapeutic Value

1. Intramuscular dosage of antipneumococcus sera in a standard dermal pneumococcic infection in rabbits is as effective as intravenous dosage provided the degree of blood stream invasion be not unusually high. 2. The immediate bactericidal effect of doses of serum given intramuscularly is equal to that of the same doses given intravenously in the cases of mild and moderately severe bacteremias. 3. The intramuscular method of serum administration in human beings with lobar pneumonia deserves a carefully controlled clinical trial.

scholarly journals Effect of polymerized type I collagen in hyperinflammation of adult outpatients with symptomatic COVID-19: a double blind, randomised, placebo-controlled clinical trial.

2021 ◽  
Author(s):  
Silvia Mendez-Flores ◽  
Angel Alexis Priego-Ranero ◽  
Daniel Azamar-Llamas ◽  
Hector Olvera-Prado ◽  
Kenia Illian Rivas-Redondo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Oxygen Saturation ◽  
Primary Outcome ◽  
Type I Collagen ◽  
Ambient Air ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Double Blind ◽  
Duration Of Symptoms

BACKGROUND Currently, therapeutic options for ambulatory COVID-19 patients are limited. OBJECTIVE To evaluate the safety, efficacy and effect of the intramuscular administration of polymerized type I collagen (PTIC) on hyperinflammation, oxygen saturation and symptom improvement in adult outpatients with symptomatic COVID-19. DESIGN Double-blind, randomised, placebo-controlled clinical trial of PTIC vs placebo. SETTING Single Third-level hospital in Mexico City (Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran) PARTICIPANTS Eighty-nine adult participants with a confirmed COVID-19 diagnosis and symptom onset within the 7 days preceding recruitment were included from August 31, 2020 to November 7, 2020 and followed for 12 weeks. Final date of follow-up was February 4, 2021. INTERVENTIONS Patients were randomly assigned to receive either 1.5 ml of PTIC intramuscularly every 12 h for 3 days and then every 24 h for 4 days (n=45), or matching placebo (n=44). MAIN OUTCOMES AND MEASURES The primary outcome was a mean reduction of at least 50% in the level of IP-10 compared to baseline. The secondary outcomes were mean oxygen saturation >92% while breathing ambient air and duration of symptoms. RESULTS Of 89 patients who were randomised, 87 (97.8%) were included in an intention-to-treat analysis; 37 (41.6%) were male and mean age was 48.5+/-14.0 years. The IP-10 levels decreased 75% in the PTIC group and 40% in the placebo group vs baseline. The comparison between treatment vs placebo was also statistically significant (P=0.0047). The IL-8 (44%, P=0.045), M-CSF (25%, P=0.041) and IL-1Ra (36%, P=0.05) levels were also decreased in the PTIC group vs baseline. Mean oxygen saturation >92% was achieved by 40/44 (90%), 41/42 (98%) and 40/40 (100%) of participants that received PTIC at 8, 15 and 97 days of follow-up vs 29/43 (67%), 31/39 (80%) and 33/37 (89%) of patients treated with placebo (P=0.001). The unadjusted accelerated failure time model showed that patients treated with PTIC achieved the primary outcome 2.70-fold faster (P<0.0001) than placebo. In terms of risk, the group of patients treated with PTIC had a 63% lower risk of having a mean oxygen saturation <92% vs placebo (P<0.0001). Symptom duration in patients treated with PTIC was reduced by 6.1+/-3.2 days vs placebo. No differences in adverse effects were observed between the groups at 8, 15 and 97 days of follow-up. CONCLUSIONS In this study, treatment with PTIC down-regulated IP-10, IL-8, M-CSF and IL-Ra levels, which could explain the PTIC effect on the higher proportion of patients with mean oxygen saturation readings > 92% and a shorter duration of symptoms as compared to patients treated with placebo. Although results are encouraging, larger randomised trials are needed.

Efficacy of maintenance therapy with zoledronic acid in patients with localized Ewing sarcoma: Report from the international Ewing 2008 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11523-11523
Author(s):  
Uta Dirksen ◽  
Raphael Koch ◽  
Vivek Bhadri ◽  
Bénédicte Brichard ◽  
Trude Butterfass-Bahloul ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Zoledronic Acid ◽  
Maintenance Therapy ◽  
Primary Endpoint ◽  
Ewing Sarcoma ◽  
Adaptive Design ◽  
Phase Iii ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Standard Risk

11523 Background: Ewing 2008R1 (EudraCT2008-003658-13, Sponsor UKM) was conducted in 12 countries. It evaluated the effect of zolendronic acid (ZOL) maintenance therapy on event-free (EFS, primary endpoint) and overall survival (OS) from randomization in standard risk Ewing Sarcoma (EwS). Methods: Phase III, open label, prospective, multi-center, randomized controlled clinical trial. Eligible patients (pts) had localized EwS with either good histological response to induction chemotherapy and/or small tumors ( < 200ml). Pts received 6 cycles VIDE induction and 8 VAI (male) or 8 VAC consolidation (female) and were randomized to receive either 9 cycles of maintenance ZOL or no further treatment (control;ctrl). ZOL cycles started parallel to the 6th consolidation cycle. Randomization was stratified by tumor site (pelvis/no pelvis). Two-sided adaptive inverse-normal 4-stage design, changed after the 1st interim analysis via Müller-Schäfer method. Initial sample size 448 pts, type I error rate 5%, power 80%. Results: 284 pts were randomized between 2009 and 2018 (142 ZOL / 142 ctrl). With a median follow-up of 3.9 years, the primary endpoint EFS was not significantly different between the ZOL and ctrl group in the adaptive design (HR 0.74, 95% CI 0.43-1.28, intention to treat). 3-year (3y) EFS rates were 84.0% (95% CI 77.7-90.8%) for ZOL vs 81.7% (95% CI 75.2-88.8%) for ctrl. Results were similar in the per protocol collective. Cause-specific HR for local recurrence in ZOL was csHR 0.30 (95% CI 0.08 -1.09; p = 0.07), for metastatic progress/new metastases csHR 1.0 (CI 0.5-2.2), for combined relapse/progress csHR 0.3 (95% CI 0.1-1.7), for second malignancies csHR 4.0 (95% CI 0.45-36.1) compared to ctrl. The 3y OS was 92.8% (95% CI 88.4-97.5%) for ZOL and 94.6% (95% CI 90.9-98.6%) for ctrl. For ZOL the 5y OS was 87.3% (95% CI 80.7-94.5%) and 89% (95% CI 83.7-95.9%) for ctrl. Noticeable more renal, neurological and gut toxicities were observed for ZOL (p < 0.05), with severe renal toxicities occurring more often in the ZOL arm (p = 0.003). Conclusions: In patients with standard risk localized Ewing Sarcoma there is no benefit from maintenance treatment with zoledronic acid, but significant side effects were observed. Clinical trial information: NCT00987636 .

scholarly journals STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA

1941 ◽  
Vol 73 (2) ◽  
pp. 201-222 ◽  
Author(s):  
W. Barry Wood
Keyword(s):  
Main Bronchus ◽  
Left Lung ◽  
Blood Stream ◽  
Pulmonary Lesion ◽  
Type I ◽  
Polymorphonuclear Leucocytes ◽  
Lobar Pneumonia ◽  
White Rats ◽  
Edema Fluid ◽  
Phagocytic Reaction

A uniformly fatal lobar pneumonia was produced in white rats by inoculation of the left main bronchus with virulent Type I pneumococci suspended in mucin. All of the animals succumbed in less than 5 days, half of them dying within 48 hours. In only 5 of 40 rats was the lesion confined to the left lung, and all but one developed pleurisy, pericarditis, or both. All had bacteriemia at the time of death. The pathogenesis of the pulmonary lesion was studied by examining the lungs of 35 rats killed at various intervals following inoculation. The pneumonic process spread rapidly until most of the left lung was involved in 36 hours. Frequent blood cultures showed invasion of the blood stream in a few rats at 6 hours and in over 90 per cent at the end of the first day. The first signs of pleurisy usually appeared at 18 hours. Microscopic examination of the actively spreading lesion revealed three characteristic zones: (1) an outer "edema zone" in which the alveoli contained many pneumococci floating freely in edema fluid, (2) a middle zone where both leucocytes and organisms were present, many of the latter being phagocytized, and (3) an inner zone of advanced consolidation in which the alveoli contained many leucocytes but no organisms and where there were already local areas of early resolution. Study of numerous lesions, at intervals of from 12 to 36 hours after inoculation, indicated that the pneumococci spread into normal alveoli principally by way of the infected edema fluid in the outer zone. Pneumococcus-laden edema fluid in large bronchi and in alveoli beneath the pleura suggested the mode of spread of the infection to other lobes and possibly to the pleural cavity. No adequate explanation could be found for the presence of active phagocytosis in the lungs of animals with bacteriemia and presumably without circulating antibodies, but this conspicuous phagocytic reaction was obviously responsible for the clearing of the central part of the spreading lesion. The action of type specific antibody upon the pulmonary lesion of experimental lobar pneumonia was studied in rats similarly infected but treated with antipneumococcal serum. When injected intravenously in a single dose within 18 hours after inoculation the antiserum was found to protect all of the rats against the otherwise fatal pneumonia. It stopped the spread of the pneumonic lesion, cleared the blood stream of organisms, and prevented the extension of early pleurisy. The antibody caused agglutination and capsular swelling of the pneumococci in the lung, particularly in the edema zone at the margin of the lesion where they were most numerous. Apparently immobilized by agglutination the organisms were overtaken by leucocytes and destroyed by phagocytosis. The phagocytic reaction was greatly accelerated by the specific opsonins of the antiserum, and the pneumococci were destroyed by polymorphonuclear leucocytes before many macrophages appeared in the alveolar exudate. Within a week after treatment resolution of the pulmonary lesion was well in progress. Both horse and rabbit antibody were shown to penetrate the lung, and immune bodies were demonstrated in the alveoli within 10 minutes after the start of treatment. The relation of the observed phenomena to the curative action of anti-pneumococcal serum has been briefly discussed, and it is pointed out that the principal effect of antiserum is to cause immobilization of the pneumococci in the advancing edema zone. Experiments to be reported in a later publication have shown that sulfapyridine exerts a similar effect through a different mechanism.

scholarly journals Preventive effect of oral magnesium in postmastectomy pain: protocol for a randomised, double-blind, controlled clinical trial

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e017986 ◽  
Author(s):  
Véronique Morel ◽  
Dominique Joly ◽  
Christine Villatte ◽  
Bruno Pereira ◽  
Gisèle Pickering
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Clinical Trial ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Preventive Effect ◽  
Double Blind ◽  
Link Type ◽  
Oral Magnesium

IntroductionBreast cancer affects 1 in 10 women worldwide, and mastectomy is a cause of chronic pain with neuropathic characteristics.N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine, memantine, dextromethorphan or magnesium are used to treat refractory pain by blocking NMDAR. Oral memantine has been shown to prevent postmastectomy pain and cognitive impact and to maintain quality of life. Likewise, the present study is intended to assess the preventive effect of oral magnesium, administered ahead of mastectomy, on the development of neuropathic pain. As a physiological blocker of NMDAR, magnesium could be an interesting candidate to prevent postoperative pain and associated comorbidities, including cognitive and emotional disorders, multiple analgesic consumption and impaired quality of life.Methods and analysisA randomised double-blind controlled clinical trial (NCT03063931) will include 100 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Magnesium (100 mg/day; n=50) or placebo (n=50) will be administered for 6 weeks, starting 2 weeks before surgery. Intensity of pain, cognitive and emotional function and quality of life will be assessed by questionnaires. The primary endpoint is pain intensity on a 0–10 numerical rating scale at 1 month postmastectomy. Data analysis will use mixed models; all tests will be two-tailed, with type-I error set at α=0.05.Ethics and disseminationThe study protocol and informed consent form were approved in December 2016 by the French Research Ethics Committee (South East VI Committee). Results will be communicated in various congresses and published in international publications.Trial registration numberNCT03063931.

scholarly journals THE RELATION OF NATURAL HUMORAL ANTIPNEUMOCOCCAL IMMUNITY TO THE INCEPTION OF LOBAR PNEUMONIA

1930 ◽  
Vol 52 (3) ◽  
pp. 421-433 ◽  
Author(s):  
O. H. Robertson ◽  
Edward E. Terrell ◽  
James B. Graeser ◽  
M. Agnes Cornwell
Keyword(s):  
Defense Mechanism ◽  
Blood Stream ◽  
Human Beings ◽  
Lobar Pneumonia ◽  
Normal Individuals ◽  
Individual Human

A study of the pneumococcidal-promoting action of the serum of lobar pneumonia patients, secured from 4 to 48 hours after the onset of the disease, has revealed the fact that in the majority of instances the serum possessed the power to promote killing of the homologous pneumococcus, isolated in different instances from the lung, blood, and sputum. While in some instances this action was slight, in others it was present to as great a degree as in normal individuals and persisted as long as 48 hours or more after the beginning of the disease. The variations observed from case to case were not related to the extent of the pneumonic lesion or to the virulence of the several pneumococcus strains but appeared to depend on differences in individual human beings in respect to the natural antipneumococcus properties of their blood and their reaction to the invading microorganism. A constant relationship was found to exist between the concentration of immune properties in the serum and blood invasion. In the presence of a well marked pneumococcidal-promoting power pneumococci were not found in the blood stream, and only when this property was greatly diminished or lost did blood invasion occur. The findings which are supported by certain previous experimental observations, indicate that lobar pneumonia can occur in the presence of a normal circulating antipneumococcus defense mechanism. From this it is inferred that before pneumococcus growth can be initiated there must be present in the lung local changes of such nature as to provide conditions for the multiplication of pneumococci protected from the pneumococcidal action of the blood. Suppositions as to the nature of these changes and the establishment of the pneumonic lesion are discussed.

Efficacy of add-on treosulfan and melphalan high-dose therapy in patients with high-risk metastatic Ewing sarcoma: Report from the International Ewing 2008R3 trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11501-11501
Author(s):  
Uta Dirksen ◽  
Vivek Bhadri ◽  
Bénédicte Brichard ◽  
Trude Butterfass-Bahloul ◽  
Sona Cyprova ◽  
...  
Keyword(s):  
Clinical Trial ◽  
High Risk ◽  
Primary Endpoint ◽  
Ewing Sarcoma ◽  
Adaptive Design ◽  
Phase Iii ◽  
Controlled Clinical Trial ◽  
High Dose ◽  
Type I ◽  
Hematopoietic Stem

11501 Background: Ewing 2008R3 (EudraCT2008-003658-13) was conducted in 12 countries. It evaluated the effect of treosulfan and melphalan high dose chemotherapy followed by re-infusion of autologous hematopoietic stem cells (HDTreoMel) on event-free (EFS, primary endpoint) and overall survival (OS) in high-risk Ewing Sarcoma (EwS). Methods: Phase III, open label, prospective, multi-center, randomized controlled clinical trial. Eligible patients (pts) had disseminated EwS with metastases to bone and/or other sites, excluding pts with only pleuropulmonary metastases. Pts received 6 cycles of VIDE induction and 8 cycles of VAC consolidation therapy. Patients were randomized to receive additional HDTreoMel chemotherapy or no further treatment (control), They were further stratified by number of bone metastases (1, 2-5, > 5). One-sided adaptive inverse-normal 4-stage design, changed after the 1st interim analysis via Müller-Schäfer method. Initial sample size 185 pts, type I error rate 2.5%, power 80%. Results: 109 pts were randomized between 2009 and 2018: 55 were randomized to HDTreoMel. With a median follow-up of 3.3 years, the primary endpoint EFS was not significantly different between HDTreoMel and control in the adaptive design (HR 0.85, 95% CI 0.55-1.32, intention-to-treat). 3-year (3y) EFS was 20.9 % (95% CI 11.5-37.9%) in HDTreoMel and 19.2 % (95% CI 10.8-34.4%) in control pts. Results were similar in the per protocol collective. Subgroup analyses showed that independent of treatment, male patients had a worse outcome than female patients: 3y EFS 13.3% (95% CI 5.7-31.1%) vs 25.2% (95% CI 15.5-40.8%); p = 0.07. Patients aged < 14 had a better outcome when treated in the HDTreoMel group: 3y EFS 39.3% (95% CI 20.4-75.8%) vs 9% (95% CI 2.4-34%); p = 0.016; HR 0.40 (0.19-0.87). These effects were similar in the per protocol collective. Severe toxicities of hematology, gut, general condition and infection were more pronounced in the HDTreoMel group (p < 0.05). Conclusions: In patients with very high risk EwS, additional HDTreoMel was of no benefit for the entire cohort of patients. HDTreoMel may be of benefit for children age < 14. This observation is supported by comparable results from a non-randomized trial EE99 R3 (Ladenstein et al. JCO, 2010). Clinical trial information: NCT00987636 .

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