Indicator Of Therapeutic Effect Research Articles

A New Specimen for Syphilis Diagnosis: Evidence by High Loads of Treponema pallidum DNA in Saliva.

BackgroundDNA from many pathogens can be detected in saliva. However, the presence and quantity of Treponema pallidum DNA in patients with syphilis in saliva is unknown.Methods234 patients with syphilis with different stages and 30 volunteers were enrolled. Paired saliva and plasma samples were collected from all participants. Consecutive saliva samples from 9 patients were collected every 4 hours following treatment. Treponema pallidum DNA in samples was determined by nested polymerase chain reaction (PCR) and droplet digital PCR targeting polA and Tpp47.Results Treponema pallidum DNA detection rates in saliva and plasma were 31.0% (9/29) and 51.7% (15/29) in primary syphilis (P = .11), 87.5% (63/72) and 61.1% (44/72) in secondary syphilis (P < .001), 25.6% (21/82) and 8.5% (7/82) in latent syphilis (P = .004), and 21.6% (11/51) and 5.9% (3/51) in symptomatic neurosyphilis (P = .021), respectively. Median (range) loads of Tpp47 and polA in saliva were 627 (0–101 200) and 726 (0–117 260) copies/mL, respectively, for patients with syphilis. In plasma, however, loads of Tpp47 and polA were low: medians (range) of 0 (0–149.6) and 0 (0–176) copies/mL, respectively. Loads of T. pallidum DNA in saliva during treatment fluctuated downward; the clearance time was positively correlated with the loads of T. pallidum DNA before treatment.ConclusionsCollection of saliva is noninvasive and convenient. The high loads of T. pallidum DNA in saliva and reduction after treatment indicated that saliva can be not only a diagnostic fluid for syphilis but also an indicator of therapeutic effectiveness.

Liver volume: a point of no return in liver transplantation?

In patients with cirrhosis, only a 75% liver volume (LV) is expected compared with age‑matched healthy individuals. Changes in LV might be an indicator of therapeutic effectiveness or disease progression. To establish whether LV is a prognostic factor in chronic liver disease irrespective of etiology and LV impacts the outcomes of liver transplant (LT). In total, 135 consecutive LT recipients were prospectively included in this study: 38 women and 97 men. The median (minimum-maximum) age was 51 (21-70) years; body mass index (BMI), 27.3 (17.3-39.2) kg/m2; Child-Pugh class (CPC), C; Model of End‑Stage Liver Disease (MELD), 16 (7-47) points; and the third lumbar vertebra skeletal muscle index (L3SMI), 47.7 (19.7-73.4) cm2/m2. Liver volume and L3SMI were calculated based on computed tomography scans at listing for LT. The receiver operating characteristic (ROC) curve was analyzed to determine the accuracy of LV in mortality prediction after LT. Liver volume differed significantly among patients in terms of chronic liver disease etiology, with the lowest values noted in those with hepatitis C virus infection. Liver volume was neither a prognostic factor of disease progression and need for LT with respect to the CPC and MELD scores nor correlated with BMI and L3SMI (P >0.05). The area under the ROC curve of LV in mortality prediction was 0.573 (95% CI, 0.403-0.743). Liver volume smaller than the median tended to be positively associated with the risk of prolonged intensive care unit stay and death (P = 0.057 and P = 0.058, respectively). Low liver volume did not seem be a point of no return in LT candidates.

PD-014 Final survival results and onset of neutropenia as an indicator of therapeutic effect in phase 2 of TAS-102 vs placebo with metastatic colorectal cancer (J003-10040030)

PD-014 Final survival results and onset of neutropenia as an indicator of therapeutic effect in phase 2 of TAS-102 vs placebo with metastatic colorectal cancer (J003-10040030)

Abstract LB-165: Early detection of the therapeutic effect in tumors treated with a thermosensitive liposome (TSL) using noninvasive ultrasound and photoacoustic imaging

Abstract The ability to assess treatment response on a case-by-case basis in a non-invasive and longitudinal manner has the potential to maximize treatment success. In this work temperature sensitive liposomes (TSLs) have been combined with non-invasive high frequency ultrasound (US) and photoacoustic (PA) imaging to assess structural (cell death) and functional (oxygenation) aspects of tumor response, indicative of therapeutic effect, within a few hours post-treatment in a preclinical model. A TSL is a drug delivery vehicle designed to release its payload at mild-hyperthermic temperatures (39-42°C). The TSL passes through the systemic circulation (37°C), until it reaches a tumor undergoing localized heating (42°C), where it releases its contents rapidly, creating a high local concentration of drug within the tumor vasculature. This leads to high tumoral drug uptake and a number of functional changes within the tumor, resulting in a therapeutic response. Conventional assessment of treatment success is measured by the change in tumor volume over time, but this may not be noticeable until several days post-treatment and no further insight into the biology of the tumor response kinetics is provided. By using US and PA imaging in a non-invasive co-registered manner, structural and functional imaging surrogates of tumor response can be visualized in 3D. These images allow the observation of changes in the first few hours post-treatment and provide both an early indication of overall therapeutic effect and insight into the kinetics of the drug-tumor interaction. Here we have used a simple 2 component TSL called HaT (Heat activated cytoToxic, DPPC/Brij78, 96:4 mol%), designed to deliver doxorubicin (DOX), which has been shown to rapidly release drug at mild-hyperthermic temperatures (100% in &amp;lt;40 s), but has good drug stability at 37°C [Tagami et al. J. Control. Release 2011, 152, 303]. A murine breast cancer model (EMT-6) implanted in the footpad of mice was imaged using the VisualSonics Vevo LAZR system at time points before and after treatment with TSL and localized heating. Co-registered, 3D US and PA images were acquired using a 40 MHz centre frequency transducer. Tumor boundaries were outlined in the US images and used to construct oxygen saturation (sO2) maps of the tumor from the PA data acquired at 750/850 nm to target the endogenous absorption of oxy/deoxy-hemoglobin. Significant changes in sO2 data (p&amp;lt;0.05) were measured within the tumor over the time course studied (0, 1, 2, 5, 24, 48, 168 h), with the greatest variation between HaT-DOX and control groups being observed between 0 and 5 h. The ability to longitudinally monitor the sO2 allows for rapid feedback on functional changes within an individual tumor on much shorter time scales (&amp;lt;5 h) than conventional tumor volume measurements. Mice tumors that received HaT-DOX treatments resulted in a &amp;gt;30% decrease in sO2 within the first 5 h post-treatment and showed &amp;gt;50% tumor regression after 14 days. Furthermore, the extent of tumor regression was observed to be proportional the magnitude of this early decrease in sO2. The observed longitudinal variations in sO2 represent the unique ability of US/PA imaging to monitor structural and functional changes within tumor vasculature and can be used as a rapid, non-invasive early indicator of HaT-DOX treatment efficacy. Citation Format: Jonathan P. May, Eno Hysi, Lauren Wirtzfeld, Elijus Undzys, Michael C. Kolios, Shyh-Dar Li. Early detection of the therapeutic effect in tumors treated with a thermosensitive liposome (TSL) using noninvasive ultrasound and photoacoustic imaging. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-165. doi:10.1158/1538-7445.AM2014-LB-165

G-CSF-producing esophageal cancer with induction of intense bone marrow FDG uptake

We report the first case of esophageal squamous cell carcinoma (SCC) producing granulocyte colony-stimulating factor (G-CSF) with induction of high uptake of (18)F-fluorodeoxyglucose (FDG) throughout the bone marrow. A close relationship between tumor status and serum G-CSF concentration was also seen. A 65-year-old man was admitted to our hospital because of esophageal SCC with leukocytosis and pyrexia. His leukocyte count and serum G-CSF concentration were 15900/μl and 140 pg/ml, respectively. Positron emission tomography/computed tomography (PET/CT) showed focal intense bone marrow (18)F-FDG uptake. Hypermetabolic activity in the bone marrow was suspected to be an effect of G-CSF. Under the diagnosis of G-CSF-producing esophageal SCC, the patient underwent minimally invasive esophagectomy in the prone position with 2-field lymph node dissection. After removal of the tumor, the leukocyte count and serum G-CSF concentration rapidly normalized. Immunohistochemically, G-CSF expression was found in the cytoplasm of tumor cells. High uptake of (18)F-FDG throughout the bone marrow decreased. The patient left the hospital on postoperative day 10 without any complications. Changes in bone marrow PET/CT findings and serum G-CSF concentration should be helpful in the definitive diagnosis of G-CSF-producing esophageal SCC and serve as an indicator of therapeutic effect.

EXPERIENCE WITH RITUXIMAB IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Objective: to analyze the efficacy of rituximab (RTM) in patients with active ankylosing spondylitis (AS) resistant to conventional therapy. Subjects and methods. The trial enrolled 10 male patients with the reliable and valid diagnosis of AS who received therapy with RTM used in cases of steadily high AS activity, resistance to standard therapy, and contraindications to the use of tumor necrosis factor-α inhibitors. The number of patients meeting the Assessment of Spondyloarthritis International Society (ASAS) criteria for 20% improvements 24 weeks after treatment initiation was the main indicator of therapeutic effectiveness. Results. After 24-week therapy, 7 and 4 of the 10 patients showed 20 and 40% improvements, respectively; and 2 patients had partial remission according to the ASAS criteria. During the treatment, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) significantly decreased (p = 0.046), the Bath Ankylosing Spondylitis Functional Index (BASFI) remained substantially unchanged. Treatment response did not depend on the development of an early (at 2 weeks) complete depletion of CD20 lymphocytes. No significant effect could be achieved in patients with high baseline BASDAI and BASFI scores. Conclusion. RTM used patients with AS can ensure clinical improvement and even remission in a number of cases; however, it is unpromising in cases of high disease activity and severe functional failure.

Delivery of an anticancer drug and a chemosensitizer to murine breast sarcoma by intratumoral injection of sulfopropyl dextran microspheres.

Intratumoral injection of controlled-release microsphere formulations of anticancer compounds has the potential to selectively increase tumour exposure to drugs. This work aimed to evaluate the therapeutic effect and toxicity of microsphere formulations containing the anticancer drug, doxorubicin, in a murine tumour model. The effect of co-administration of verapamil, a P-glycoprotein modulator or chemosensitizer, was investigated. Initial in-vitro studies confirmed the ability of verapamil to enhance the accumulation of both doxorubicin and [(99mTc)]sestamibi, also a P-glycoprotein substrate, in EMT6 murine breast sarcoma cells and a doxorubicin-selected multidrug-resistant variant, EMT6/AR1.0. Ex-vivo studies using confocal microscopy demonstrated release of doxorubicin from microspheres and diffusion of the drug through tissue. For in-vivo studies, EMT6 and EMT6/AR1.0 cells were grown in BALB/c mice. Following intratumoral injection of doxorubicin-loaded microspheres, alone or in combination with verapamil-loaded microspheres, the tumour diameter was measured serially as an indication of therapeutic effect, while the weight, appearance, and behaviour of the mice were monitored as an indication of general toxicity. Intratumoral injections of doxorubicin-loaded microspheres were tolerated much better than systemic administration of equivalent drug concentrations. There was a modest (up to 34%) delay of tumour growth compared with groups receiving no treatment or blank microspheres. Co-injection of verapamil microspheres with doxorubicin microspheres produced a moderate increase in toxicity but no further delay in tumour growth. Controlled-release microsphere formulations of anticancer agents administered intratumorally were an efficient way to deliver high drug doses to the tumour with little systemic toxicity.

In vivo efficacy and toxicity of intratumorally delivered mitomycin C and its combination with doxorubicin using microsphere formulations

The efficacy and toxicity of intratumorally (i.t.) administered anticancer drugs mitomycin C (MMC) and doxorubicin (Dox) incorporated in polymeric microspheres were investigated. Biodegradable sulfopropyl dextran microspheres and their oxidized products were used to load Dox and MMC, respectively. EMT6 mouse mammary cancer cells were injected into the hind leg of BALB/c mice. MMC microspheres, alone or combined with Dox microspheres, were injected i.t. once tumors had reached around 0.3 g. The tumor-plus-leg diameter was measured daily and the delay in time for the tumor to grow to 1.13 g relative to control (TGD) was employed as an indication of therapeutic effect. General toxicity was determined by monitoring weight, appearance and behavior of the mice. Morphology and histology of tumor and heart tissues were also examined. An average 79% TGD was observed after i.t. injection of MMC microspheres. The i.t. co-administration of MMC and Dox microspheres resulted in a 185% TGD. The i.t. injections of the microsphere formulations did not result in visible signs of toxicity in animals. In contrast, systemic (i.e. i.p.) injections of MMC solutions caused considerable general toxicity. This study suggests that i.t. delivery of anticancer drugs by polymeric microspheres is an effective way of improving the therapeutic index for cancer chemotherapy of selected solid tumors under special conditions.

Achalasia: the usefulness of manometry for evaluation of treatment.

Although manometry is used with increasing frequency to evaluate the effectiveness of different treatments for achalasia, the criteria for a successful manometric response have not been well defined. Manometric responses were collected before and after 43 treatments in 35 patients with achalasia in order to determine manometric changes after different clinical outcomes: 15 unsuccessful outcomes and 28 successful outcomes were reported. In the latter, resting pressure of the lower esophageal sphincter decreased to 12.8 mm Hg, whereas in unsuccessful outcomes this was significantly higher (28.2 mm Hg). A decrease of lower esophageal sphincter pressure below 17 mm Hg or more than 40% of the pretreatment level was associated with successful outcomes. Our data suggest that manometry is a good indicator of therapeutic effectiveness and we propose that it be used systematically for objective evaluation of achalasia treatment.

Effects of Epinephrine and Ritodrine in Dogs With Acute Hyperkalemia

As plasma potassium concentrations, whether normal or elevated, can be reduced by intravenous administration of either epinephrine or ritodrine, the effects of these drugs were examined during acute hyperkalemia. Six anesthetized dogs were studied every 2 wk, on 18 separate occasions. Hyperkalemia was induced by intravenous infusion of potassium chloride, resulting in plasma potassium concentrations of 9.6 +/- 0.3 mEq/L (mean +/- SEM), bradycardia, and idioventricular rhythm. Dogs were then given slow intravenous injections every 30 min of either saline (controls), epinephrine, or ritodrine. Epinephrine doses were 0.01, 0.1, 1.0, 10, or 100 micrograms/kg; ritodrine doses were 0.1, 1.0, 10, 100, or 1000 micrograms/kg. At the highest does, both epinephrine and ritodrine caused clinically important decreases in plasma potassium, reducing concentrations to below 7.0 mEq/L. Ritodrine had a significantly greater effect than epinephrine. Side effects included hypertension and dysrhythmias with epinephrine, serious hypotension with ritodrine, and tachycardia with both drugs. For both drugs, the doses that caused a decrease in plasma potassium also caused an increase in heart rate and there was a correlation between plasma potassium levels and heart rate. Epinephrine and ritodrine may be useful in treating acute hyperkalemia, but cardiovascular side effects may occur. Increased heart rate could be used as an indicator of therapeutic effect and the magnitude of the increase in heart rate may be helpful in predicting the level of response.

Positron emission tomographic evaluation of radiochemotherapeutic effect on regional cerebral hemocirculation and metabolism in patients with gliomas.

Hemocirculatory and metabolic changes in tumor regions and the remote brain structure were analyzed using oxygen-15 and fluorine-18 positron emission tomography (PET) in eight patients with gliomas after radiation and chemotherapy of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and N-(2-tetrahydrofuryl)-5-fluorouracil (FT-207). In the tumor regions after the radiochemotherapy, regional cerebral blood flow (rCBF) and cerebral blood volume (rCBV) varied widely and there was a tendency for oxygen consumption (rCMRO2) to fall. The change in glucose consumption (rCMRG1) was especially noteworthy with regard to clinical correlations. Six patients with decreased rCMRG1 values had 16% to 29% regressions in tumor size measured by X-ray computerized tomography (CT), and showed some period of clinical relief. In contrast, one patient with an increased rCMRG1 value had some progression of tumor growth, and there were no clinical amelioration. The hemocirculation and metabolism of the contralateral gray matter seem to fluctuate by various factors as intracranial pressure and the effectiveness of the therapy. In gliomas therapy, tumor rCMRG1 values can be a good indicator of therapeutic effectiveness.

Increase in serum osteocalcin concentration is a slow indicator of therapeutic effect in children treated for somatotropin deficiency.

Increase in serum osteocalcin concentration is a slow indicator of therapeutic effect in children treated for somatotropin deficiency.

Serum procollagen-III as indicator of therapeutic effect in children treated for somatotropin deficiency.

Journal Article Serum procollagen-III as indicator of therapeutic effect in children treated for somatotropin deficiency. Get access G Lindstedt, G Lindstedt Search for other works by this author on: Oxford Academic Google Scholar L Weijkum, L Weijkum Search for other works by this author on: Oxford Academic Google Scholar P A Lundberg, P A Lundberg Search for other works by this author on: Oxford Academic Google Scholar K Albertsson-Wikland K Albertsson-Wikland Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 30, Issue 11, 1 November 1984, Pages 1879–1880, https://doi.org/10.1093/clinchem/30.11.1879 Published: 01 November 1984

A note on the use of the phallometric method of measuring mild sexual arousal in the male

The phallometric test involves the measurement of minimal penis volume changes in subjects exposed to certain stimulus-configurations. At present this procedure seems to be the most valid method of measuring degree of mild sexual arousal in the male. However, many subjects are able intentionally to influence the outcome of the test to some degree by inhibiting psychophysiological reactions. Therefore, unintentional distortions of test results are to be expected also; for instance, inhibiting reactions to objects which are not socially approved as being proper objects of erotic interest. These possible influences on the test results have to be taken into account when applying the phallometric method as an indicator of therapeutic effect. The observance of certain conditions in applying the test and the use of sophisticated research design are necessary to avoid pitfalls of interpretation.

Relative effectiveness of certain drugs against shock produced in mice from tourniquet and burn trauma.

The therapeutic effectiveness of chlorpromazine, dibenamine, l-norepinephrine, 1-ethylsulfonyl-4-ethyl-piperazine hydrochloride, serotonin, ascorbic acid, human plasma cholinesterase and a bacterial polysaccharide (Piromen), has been studied in experimental tourniquet and burn shock in mice. Employing survival as an indication of therapeutic effect, simultaneous comparisons were made of the survival of groups of animals receiving these agents in saline and control groups receiving saline alone. Chlorpromazine pretreatment (8–20 mg/kg) produced reproducible positive effects on survival whether given alone or in conjunction with saline replacement therapy. Dibenamine pretreatment (5–25 mg/kg) produced positive effects on survival but this response was not always reproducible. No beneficial effect was demonstrable following administration of the remainder of these agents when compared to control groups given saline alone.