Annals of the New York Academy of Sciences
-
Ann. N. Y. Acad. Sci. · Jul 2013
ReviewDevelopment of ipilimumab: a novel immunotherapeutic approach for the treatment of advanced melanoma.
The immunotherapeutic agent ipilimumab has helped address a significant unmet need in the treatment of advanced melanoma. Ipilimumab is a fully human monoclonal antibody that targets cytotoxic T-lymphocyte antigen-4 (CTLA-4), thereby augmenting antitumor immune responses. After decades in which a number of clinical trials were conducted, ipilimumab was the first therapy to improve overall survival in a randomized, controlled phase III trial of patients with advanced melanoma. ⋯ These immune-related adverse events were mostly reversible when effective treatment guidelines were followed. Importantly, long-term follow-up of patients who received ipilimumab in a phase III trial showed that 24% survived at least two years, and in phase II studies, a proportion of patients survived at least five years. Evaluation of ipilimumab is ongoing in the adjuvant setting for melanoma, and for advanced disease in nonsmall cell lung, small cell lung, prostate, ovarian, and gastric cancers.
-
The human experience of pain is multidimensional and comprises sensory, affective, and cognitive dimensions. Preclinical assessment of pain has been largely focused on the sensory features that contribute to nociception. The affective (aversive) qualities of pain are clinically significant but have received relatively less mechanistic investigation in preclinical models. ⋯ An important advance of such operant behaviors is that these approaches may allow the detection and mechanistic investigation of spontaneous neuropathic or ongoing inflammatory/nociceptive (i.e., nonevoked) pain that is otherwise difficult to assess in nonverbal animals. Operant measures may allow the identification of mechanisms that contribute differentially to reflexive hypersensitivity or to pain affect and may inform the decision to progress novel mechanisms to clinical trials for pain therapy. Additionally, operant behaviors may allow investigation of the poorly understood mechanisms and neural circuits underlying motivational aspects of pain and the reward of pain relief.
-
Ann. N. Y. Acad. Sci. · Apr 2013
ReviewManaging obesity in primary care practice: a narrative review.
This narrative review examines randomized controlled trials of the management of obesity in primary care practice, in light of the Centers for Medicare and Medicaid Services' decision to support intensive behavioral weight loss counseling provided by physicians and related health professionals. Mean weight losses of 0.1-2.3 kg were observed with brief (10- to 15-min) behavioral counseling delivered by primary care providers (PCPs) at monthly to quarterly visits. Losses increased to 1.7-7.5 kg when brief PCP counseling was combined with weight loss medication. ⋯ Remotely delivered, intensive (>monthly contact) behavioral counseling, as offered by telephone, yielded losses of 0.4-5.1 kg over the same period. Further study is needed of the frequency and duration of visits required to produce clinically meaningful weight loss (>5%) in primary care patients. In addition, trials are needed that examine the cost-effectiveness of PCP-delivered counseling, compared with that potentially provided by registered dietitians or well-studied commercial programs.
-
Ann. N. Y. Acad. Sci. · Apr 2013
ReviewCardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials.
The relationship between glucose control and cardiovascular outcomes in type 2 diabetes has been a matter of controversy over the years. Although epidemiological evidence exists in favor of an adverse role of poor glucose control on cardiovascular events, intervention trials have been less conclusive. ⋯ The benefit of strict glucose control on cardiovascular outcomes and mortality may be indeed hampered by the extent and frequency of hypoglycemic events and could be enhanced if glucose-lowering medications, capable of exerting favorable effects on the cardiovascular system, were used. This review examines the relationship between intensive glucose control and cardiovascular outcomes in type 2 diabetes, addressing the need for individualization of glucose targets and careful consideration of the benefit/risk profile of antidiabetes medications.
-
Ann. N. Y. Acad. Sci. · Mar 2013
ReviewPre- and postsynaptic inhibitory control in the spinal cord dorsal horn.
Sensory information transmitted to the spinal cord dorsal horn is modulated by a complex network of excitatory and inhibitory interneurons. The two main inhibitory transmitters, GABA and glycine, control the flow of sensory information mainly by regulating the excitability of dorsal horn neurons. A presynaptic action of GABA has also been proposed as an important modulatory mechanism of transmitter release from sensory primary afferent terminals. By inhibiting the release of glutamate from primary afferent terminals, activation of presynaptic GABA receptors could play an important role in nociceptive and tactile sensory coding, while changes in their expression or function could be involved in pathological pain conditions, such as allodynia.