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The purpose of this study was to summarize the progress made using fast neutron irradiation in the treatment of prostate cancer at Wayne State University between 1991 and the year 2001. The results of three Phase II studies and one Phase III st udy involving nearly 700 patients is summarized in this paper. The Phase II studies weredose finding studies looking at doses of 15, 9, 10, and 11 nGy, respectively. The randomized protocol was a study of sequence looking at the results of treating patients with neutron first versus neutron radiation last. The results demonstrated that the best combination of tumor control probabilities and normal tissue complications was found in a mix of approximately 50% neutrons and 50% photons. Thus, the standard doses become 10 nGy and 40 Gy of photons. The randomized trial demonstrated that the sequence has significant importance and the disease-free survival was 93% for patients treated with neutrons first versus 73% for patients treated with neutrons last. There was no difference in the rate of acute or chronic complications. Finally, an analysis was performed demonstrating which patients may best benefit from the use of neutron irradiation. It was shown that patients with one, two, or three adverse risk factors had a significant improvement in disease-free survival when part of the treatment included neutron radiation versus standard photon radiation alone. Neutron radiation can be delivered safely with effort to see that it is superior to that which can be achieved by conformal photon irradiation by itself. Future work will be done to expand the role of neutron radiation in other clinical disease sites.

To circumvent the toxicity caused by systemic injection of cytokines, cytokine cDNA genes encoding the human interleukin IL-2 cDNA (Ad-IL-2) and murine interferon IFN- γ gene (Ad- IFN- γ ) were inserted into adenoviral vectors. These constructs were used for intratumoral gene therapy of murine renal adenocarcinoma Renca tumors. Treatment with three doses of Ad-IL-2 or Ad- IFN- γ , given a day apart, was more effective than single-dose gene therapy. We found that tumor irradiation enhanced the therapeutic efficacy of Ad-IL-2 and Ad-IFN- γ intratumoral gene therapy. Tumor irradiation, administered 1 day prior to three doses of Ad-IL-2 treatment, was more effective than radiation or Ad-IL-2 alone, resulting in tumor growth arrest in all mice, increased survival and a consistent increase in complete tumor regression response rate. Complete responders rejected Renca tumor challenge and demonstrated specific cytotoxic T-cell activity, indicative of specific tumor immunity. The effect of radiation combined with three doses of Ad-IFN- γ was less pronounced and did not lead to tumor immunity. Histological observations showed that irradiation of the tumor prior to gene therapy increased tumor destruction and inflammatory infiltrates in the tumor nodules. These findings demonstrate that tumor irradiation improves the efficacy of Ad-IL-2 gene therapy for induction of antitumor immune response.

The results of clinical trials in the treatment of adenocarcinoma of the prostate using, mixed beam neutron/photon therapy, neutrons alone and photon therapy in combination with hormone treatment are compared. These trials indicate that neutron therapy is superior to photon/hormone therapy in achieving local control. The costs of delivering these two different therapies in a large US academic radiation oncology center at Wayne State University (WSU) are compared. The cost of a full course of mixed beam therapy is $20,142 compared to $18,871 for the photon/hormone treatment. Although the WSU neutron facility is a state-of-the-art installation, it is also a prototype device; it is estimated that a modern neutron facility based on this design would operate more cost effectively reducing the cost of a course of mixed beam therapy to $18,532.

The conditions for safe and effective conformal neutron radiotherapy have been established at Wayne State University.The conditions for safe and effective conformal neutron radiotherapy have been established at Wayne State University.

The purpose of this study was to summarize the progress made using fast neutron irradiation in the treatment of prostate cancer at Wayne State University between 1991 and the year 2001. The results of three Phase II studies and one Phase III study involving nearly 700 patients is summarized in this paper. The Phase II studies were dose finding studies looking at doses of 15, 9, 10, and 11 nGy, respectively. The randomized protocol was a study of sequence looking at the results of treating patients with neutron first versus neutron radiation last. The results demonstrated that the best combination of tumor control probabilities and normal tissue complications was found in a mix of approximately 50% neutrons and 50% photons. Thus, the standard doses become 10 nGy and 40 Gy of photons. The randomized trial demonstrated that the sequence has significant importance and the disease-free survival was 93% for patients treated with neutrons first versus 73% for patients treated with neutrons last. There was no diff erence in the rate of acute or chronic complications. Finally, an analysis was performed demonstrating which patients may best benefit from the use of neutron irradiation. It was shown that patients with one, two, or three adverse risk factors had a significant improvement in disease-free survival when part of the treatment included neutron radiation versus standard photon radiation alone. Neutron radiation can be delivered safely with effort to see that it is superior to that which can be achieved by conformal photon irradiation by itself. Future work will be done to expand the role of neutron radiation in other clinical disease sites.

Hidradenitis suppurativa is a painful, chronic inflammatory skin disease. In two double-blind, placebo-controlled trials, treatment with adalimumab resulted in significantly increased rates of clinical response at week 12. Rates of serious adverse events were similar between groups. Hidradenitis suppurativa, also known as acne inversa, is a painful, chronic inflammatory skin disease 1 – 3 characterized by multifocal, recurrent nodules, abscesses, and fistulas, predominantly affecting the axillary, inguinal, breast-fold, and anogenital regions. 4 The prevalence of self-reported disease is 1% in Western Europe. 1 , 5 The average interval from the onset of symptoms to diagnosis is 7.2 years. 6 Women are affected 2 to 5 times as frequently as men, and the disease may be more common in blacks than in whites. 1 , 7 Disease severity ranges from mild (localized lesions) to severe (multiple areas of widely dispersed lesions, including interconnected sinus tracts and . . .

The “10% rule” of handedness asserts the dominant hand is 10% stronger than the non-dominant hand. Primarily derived from handgrip data, it is unclear if a generalized asymmetry exists across the upper limb. Understanding how strength asymmetry may be affected by handedness, sex, and exertion type has important implications for ergonomics design, sports performance, and clinical rehabilitation. The purpose of this study was to systematically synthesize currently available evidence examining upper limb strength asymmetry. 10,061 results were retrieved, and 174 studies remained after title/abstract screening. 87 studies were synthesized. Results are compiled by exertion type and manner of asymmetry comparison (i.e. right/left, dominant/non-dominant). Asymmetry ratios were calculated to examine the effects of handedness, exertion side, arm region, and sex. Strength differences were most frequently reported for grip exertions (n = 49). 25 studies reported other joint strength asymmetries. Overall, the right limb was 6.7% stronger than the left limb (n = 9342) and the dominant limb was 11.6% stronger than the non-dominant limb (n = 9327), though strength asymmetry varied across joints and movements (2.1% to 19.5%). This research demonstrates that the 10% rule is a good approximation for upper limb strength asymmetry. However, several factors, including joint, movement type, and sex, can affect this relationship.

Summary Patients with advanced solid malignancies were enrolled to an open-label, single-arm, dose-escalation study, in which CRLX101 was administered intravenously over 60 min among two dosing schedules, initially weekly at 6, 12, and 18 mg/m 2 and later bi-weekly at 12, 15, and 18 mg/m 2 . The maximum tolerated dose (MTD) was determined at 15 mg/m 2 bi-weekly, and an expansion phase 2a study was completed. Patient samples were obtained for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Response was evaluated per RECIST criteria v1.0 every 8 weeks. Sixty-two patients (31 male; median age 63 years, range 39–79) received treatment. Bi-weekly dosing was generally well tolerated with myelosuppression being the dose-limiting toxicity. Among all phase 1/2a patients receiving the MTD ( n  = 44), most common grade 3/4 adverse events were neutropenia and fatigue. Evidence of systemic plasma exposure to both the polymer-conjugated and unconjugated CPT was observed in all treated patients. Mean elimination unconjugated CPT T max values ranged from 17.7 to 24.5 h, and maximum plasma concentrations and areas under the curve were generally proportional to dose for both polymer-conjugated and unconjugated CPT. Best overall response was stable disease in 28 patients (64 %) treated at the MTD and 16 (73 %) of a subset of NSCLC patients. Median progression-free survival (PFS) for patients treated at the MTD was 3.7 months and for the subset of NSCLC patients was 4.4 months. These combined phase 1/2a data demonstrate encouraging safety, pharmacokinetic, and efficacy results. Multinational phase 2 clinical development of CRLX101 across multiple tumor types is ongoing.

Background Alcohol use is common among persons living with HIV (PLWH), who often experience chronic pain, yet its impact on pain and opioid misuse is not fully characterized. Methods We assessed associations between hazardous alcohol use and pain interference, defined as the self-reported impact of pain on daily living, pain severity, and risk for opioid misuse among PLWH who were on long-term opioid therapy (LTOT). A cohort was recruited as part of the “Targeting Effective Analgesia in Clinics for HIV” (TEACH) study, a randomized controlled trial to improve LTOT in HIV clinics. The Alcohol Use Disorders Test (AUDIT), Brief Pain Inventory (BPI) and the Current Opioid Misuse Measure (COMM) were administered at both baseline and 12-months. Linear mixed and generalized estimating equation models, incorporating data from both time points, evaluated associations between hazardous alcohol use (AUDIT ≥8) and: pain interference (0–10), pain severity (0–10), and opioid misuse risk (COMM ≥13), adjusting for age, gender, depressive symptoms, use of non-alcohol substances, time-point, and study-arm. Results The sample was comprised of 166 participants, of which 31 (19%) reported hazardous alcohol use. The majority were male (65%), black (72%), and the mean age was 54 (range: 29–77). Hazardous alcohol use was significantly associated with higher pain interference (adjusted mean difference [AMD]: 1.02; 95% CI: 0.08, 1.96) and higher odds of opioid misuse risk (AOR: 3.73, 95% CI: 1.88–7.39), but not pain severity (AMD: 0.47, 95% CI: − 0.35, 1.29). Conclusions Hazardous alcohol use was associated with greater functional impairment in daily living from their pain and higher odds for prescription opioid misuse in this study of PLWH on LTOT. Providers should be attentive to alcohol use among PLWH who are prescribed opioids given associations with pain and opioid misuse. Trial registration ClinicalTrials.gov NCT02564341 (Intervention, September 30, 2015) and NCT02525731 (Patient Cohort, August 17, 2015). Both prospectively registered.