Mechanisms of Musculoskeletal Frailty in People Living with HIV.

People over age 50 living with HIV experience frailty including functional declines and illnesses usually attributed to aging, more frequently and ten years earlier than people without HIV. As the number of people living with HIV over age 50 is expected to triple by the year 2040, those experiencing early frailty will continue to grow. This review synthesizes the known correlates and contributors to musculoskeletal frailty in people living with HIV. A conceptual model of musculoskeletal frailty in HIV that outlines chronic inflammation, altered energy metabolism, immune activation, and endocrine alterations as mechanisms associated with frailty development is presented. Additionally, the potential ability of aerobic exercise to modify the risk of frailty is highlighted as an important intervention.

Bortezomib treatment produces nocifensive behavior and changes in the expression of TRPV1, CGRP, and substance P in the rat DRG, spinal cord, and sciatic nerve.

To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration of bortezomib and a well-established "chronic" schedule in a rat model of bortezomib-induced PN. The TRPV1 channel and sensory neuropeptides CGRP and substance P (SP) were studied in L4-L5 dorsal root ganglia (DRGs), spinal cord, and sciatic nerve. Behavioral measures, performed at the end of the chronic bortezomib treatment, confirmed a reduction of mechanical nociceptive threshold, whereas no difference occurred in thermal withdrawal latency. Western blot analysis showed a relative increase of TRPV1 in DRG and spinal cord after both acute and chronic bortezomib administration. Reverse transcriptase-polymerase chain reaction revealed a decrease of TRPV1 and CGRP mRNA relative levels after chronic treatment. Immunohistochemistry showed that in the DRGs, TRPV1-, CGRP-, and SP-immunoreactive neurons were mostly small- and medium-sized and the proportion of TRPV1- and CGRP-labeled neurons increased after treatment. A bortezomib-induced increase in density of TRPV1- and CGRP-immunoreactive innervation in the dorsal horn was also observed. Our findings show that bortezomib-treatment selectively affects subsets of DRG neurons likely involved in the processing of nociceptive stimuli and that neurochemical changes may contribute to development and persistence of pain in bortezomib-induced PN.

Photodynamic therapy of multiple actinic keratoses: reduced pain through use of visible light plus water-filtered infrared A compared with light from light-emitting diodes.

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is an effective treatment for multiple actinic keratoses (AKs). Pain, however, is a major side-effect. OBJECTIVES: To compare pain intensity, efficacy, safety and cosmetic outcome of MAL PDT with two different light sources in an investigator-initiated, randomized, double-blind study. METHODS: Eighty patients with multiple AKs grade I-II were assigned to two groups: group 1, MAL PDT with visible light and water-filtered infrared A (VIS+wIRA); group 2, MAL PDT with light from light-emitting diodes (LEDs), with a further division into two subgroups: A, no spray cooling; B, spray cooling on demand. MAL was applied 3 h before light treatment. Pain was assessed before, during and after PDT. Efficacy, side-effects, cosmetic outcome and patient satisfaction were documented after 2 weeks and 3, 6 and 12 months. Where necessary, treatment was repeated after 3 months. RESULTS: Seventy-six of the 80 patients receiving MAL PDT completed the study. Patient assessment showed high efficacy, very good cosmetic outcome and high patient satisfaction. The efficacy of treatment was better in the group of patients without spray cooling (P=0·00022 at 3 months, P=0·0068 at 6 months) and showed no significant differences between VIS+wIRA and LED. VIS+wIRA was significantly less painful than LED: the median of maximum pain was lower in the VIS+wIRA group than in the LED group for PDT without spray cooling. Pain duration and severity assessed retrospectively were less with VIS+wIRA than with LED, irrespective of cooling. CONCLUSIONS: All treatments showed high efficacy with good cosmetic outcome and high patient satisfaction. Efficacy of treatment was better without spray cooling. VIS+wIRA PDT was less painful than LED PDT for PDT without spray cooling.

Amoxicillin-induced exanthema in young adults with infectious mononucleosis: demonstration of drug-specific lymphocyte reactivity.

BACKGROUND: Teenagers and young adults frequently develop maculopapular exanthema following amoxicillin intake within infectious mononucleosis. The underlying pathomechanisms are still largely unknown. OBJECTIVES: To investigate whether amoxicillin-induced exanthema in florid infectious mononucleosis is a disease-associated phenomenon or results from specific sensitization to the drug. METHODS: Four patients with amoxicillin-induced exanthema within infectious mononucleosis were analysed in vivo by prick, intradermal and patch tests and in vitro by means of the lymphocyte transformation test (LTT) employing amoxicillin, ampicillin, benzylpenicillin and phenoxymethylpenicillin. RESULTS: Drug-specific sensitization to amoxicillin in the LTT was observed in three patients, two of whom showed a side-chain-specific sensitization to amoxicillin and ampicillin. The in vitro results were confirmed in vivo by skin tests. CONCLUSIONS: These data suggest that real sensitization to amoxicillin and ampicillin may occur within infectious mononucleosis and may be detected in vivo and in vitro by means of skin tests and the LTT.