Intramural vesicular fat--an uncommon CT finding

We present a case of a 75-year-old male who presented with lower back pain found to have an incidental finding of intramural vesicular fat on an unenhanced computed tomography of the pelvis. This relatively uncommon finding of a normal entity should not be mistaken for other causes of pathology within the urinary bladder.     

Treatment options for articular cartilage defects of the knee

The treatment of symptomatic articular cartilage defects of the knee has evolved tremendously in the past decade. Previously, there were limited treatment options available to patients who suffered from either partial-thickness or full-thickness cartilage lesions. Because articular cartilage has a limited capacity for healing, patients were often treated symptomatically until they became candidates for osteotomy or total joint replacement. Recently, both reparative and restorative procedures have been developed to address this significant source of morbidity in young active patients. Microfracture is a reparative technique that induces a healing response to occur in an area of articular cartilage damage. Osteochondral autografts and allografts in addition to autologous chondrocyte implantation are restorative techniques aimed at recreating a more normal articular surface. Both types of procedures have been developed to alleviate the symptoms associated with focal chondral defects, as well as limit their potential to progress to a diffuse degenerative arthritis. Treatment can vary depending on both cartilage defect and patient factors. This article summarizes the various treatment options that have recently become available.     

Neuroendocrine evidence that (S)-2-(chloro-5-fluoro-indol- l-yl)-1-methylethylamine fumarate (Ro 60-0175) is not a selective 5-hydroxytryptamine(2C) receptor agonist

The 5-hydroxytryptamine(2A) and (2C) (5-HT(2A) and 5-HT(2C)) receptors are so closely related that selective agonists have not been developed until recently with the advent of (S)-2-(chloro-5-fluoro-indol-l-yl)-1-methylethylamine fumarate (Ro 60-0175), a putatively selective 5-HT(2C) receptor agonist. In the present study, Ro 60-0175 was used to analyze the importance of 5-HT(2C) receptors in hormone secretion. Injection of Ro 60-0175 (5 mg/kg s.c.) produced a maximum increase in plasma levels of adrenocorticotrophic hormone, oxytocin, and prolactin at 15 min postinjection and a maximum increase in plasma corticosterone levels at 60 min postinjection. Ro 60-0175-mediated increases in plasma hormone levels were dose-dependent (corticosterone ED(50) = 2.43 mg/kg; oxytocin ED(50) = 4.19 mg/kg; and prolactin ED(50) = 4.03 mg/kg). To assess the role of 5-HT(2C) and 5-HT(2A) receptors in mediating the hormone responses to Ro 60-0175, rats were pretreated with the 5-HT(2C) antagonist 6-chloro-5-methyl-1-[2-(2-methylpyridyl-3-oxy)-pyrid-5-yl carbonyl] indoline (SB 242084) or 5-HT(2A) antagonists (+/-)-2,3-dimethoxyphenyl-1-[2-4-(piperidine)-methanol] (MDL 100,907) before injection of Ro 60-0175 (5 mg/kg s.c.). Neither SB 242084 (0.1, 0.5, 1, and 5 mg/kg i.p.) nor MDL 100,907 (1, 5, and 10 microg/kg s.c.) significantly inhibited the Ro 60-0175-induced increases in plasma hormone levels. The data suggest that Ro 60-0175 increases hormone secretion by mechanisms independent of the activation of 5-HT(2C) and/or 5-HT(2A) receptors and suggest that Ro 60-0175 is not a highly selective 5-HT(2C) receptor agonist.     

Reversibility of severe metabolic stress in stored platelets after in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival

BACKGROUND: Determining reversible aspects of the platelet storage lesion may result in improved function and survival of transfused platelets. STUDY DESIGN AND METHODS: Using a model of high-dose (apheresis-derived) platelet concentrates (PC), functional changes imposed by transient adverse metabolic conditions (pH < 6.0 for 1-2 hr) that could be reversed by autologous plasma rescue followed by standard platelet storage were investigated. Whole-blood-derived PCs were transfused into a small number of normal volunteers to determine platelet recovery and survival. RESULTS: Without rescue, high-dose PCs developed severe in vitro functional derangements at the time of the pH nadir including 1) loss of resting morphology; 2) complete abrogation of osmotic recovery and platelet aggregation and glycoprotein IIb/IIIa up-regulation to agonist; and 3) decreased alpha-granule release. By contrast, spontaneous and agonist-induced binding of annexin V were unaffected by adverse metabolic conditions. Plasma rescue to an optimal pH improved morphology scores, stabilized osmotic recovery, and completely restored platelet secretory responses, as measured by aggregation, glycoprotein IIb/IIIa up-regulation, and alpha-granule release. In a limited number of studies, plasma rescue was accompanied by preserved in vivo platelet recovery and survival after autologous transfusion after 5 days of storage. CONCLUSION: Transient derangement of platelet metabolism, which does not increase membrane phosphatidylserine exposure, causes in vitro functional abnormalities that are fully reversed or stabilized by metabolic rescue. Preliminary data suggest that such rescued platelets may have normal posttransfusion recovery and survival.     

Effectiveness of budesonide administered via dry-powder inhaler versus triamcinolone acetonide administered via pressurized metered-dose inhaler for adults with persistent asthma in managed care settings

BACKGROUND: Clinical studies have demonstrated the efficacy and relative safety of inhaled corticosteroids in the treatment of asthma. However, effectiveness and cost-effectiveness comparisons of available inhaled corticosteroids in real-life clinical settings are lacking. OBJECTIVE: This study compared the effectiveness and safety of budesonide administered via dry-powder inhaler versus that of triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adult patients with persistent asthma treated in a managed care setting. METHODS: This was a randomized, open-labe, 52-week study of adult patients (aged >or= 18 years) with persistent asthma enrolled in 25 US health plans. The primary study outcome was mean change from baseline to the end of treatment in symptom-free days. Secondary variables were changes from baseline in number of episode-free days, episode-free days at 52 weeks, forced expiratory volume in 1 second (FEV(1)), forced vital capacity, asthma symptom scores, breakthrough bronchdilator use, patient discontinuations, and health-related quality of life. Patients were issued diaries in which to record use of study medication and concomitant asthma medication use, as well as daytime and nighttime asthma symptom severity. Patients were assessed at weeks 4, 13, 26, 39, and 52. Safety was assessed based on adverse events and changes in laboratory tests, vital signs, and physical examinations. RESULTS: A total of 945 patients (344 men, 601 women; mean [SD] age, 46.8 [14] years) were enrolled; 631 received budesonide and 314 received triacinolane acetonide. Improvements in all effectiveness variables were observed with both treatments. The mean increase from baseline in the number of symptom-free days per month assessed at month 12 was 7.74 (95% CI, 6.81-8.66) for patients receiving budesonide and 3.78 (95% CI, 2.47-5.09) for patients receiving triamcinoline acetonide ( P<0.001). The estimated annual mean (SD) number symptom-free days for patients receiving budesonide was 141.1 (125.0) over the treatment phase, compared with 99.3 (112.1) for those receiving triamcinolone acetonide (P<0.001). Patients receiving budesonide demonstrated significant improvements (compared with those receiving triamcinolone acetonide) in overall quality of life, daytime and nighttime asthma symptom severity, breakthrough bronchodilator use, and FEV(1) (all P<0.001). Safety measures were similar between groups. CONCLUSION: In these managed care settings, budesonide inhalation powder administered via dry-powder inhaler was significantly more effective than triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adults with persistent asthma.     

Changes in serum lipoprotein profile during interferon therapy in chronic hepatitis C

OBJECTIVES: Therapy with a interferon is associated with a rise in serum triglyceride levels, although this effect has not been well studied with newer forms of interferon or interferon in combination with ribavirin. METHODS: Review of combined data obtained from several prospective, randomized controlled clinical trials conducted in the clinical studies unit of a tertiary care referral center among patients with chronic hepatitis C undergoing treatment with various forms of a interferon, with or without the addition of ribavirin. Serum levels of triglycerides and cholesterol were measured before and during therapy. Changes in these levels were correlated with baseline characteristics. RESULTS: At baseline, the mean serum triglyceride level among 152 patients studied was 130 mg/dL (range 32-620) and was elevated above normal in three patients (2%). During therapy, triglyceride levels rose significantly early on and began to decline spontaneously after 12 wk, returning to baseline after stopping treatment. Triglyceride levels rose above 500 mg/dL in 18 patients (12%) and above 1000 mg/dL in two patients (1.3%) although none experienced acute complications or clinical symptoms. Serum cholesterol levels did not change significantly during therapy (mean at baseline 172 vs 168 mg/dL at 24 wk). Factors correlated with the rise in triglycerides included baseline triglyceride levels, HCV genotype, and the type of interferon used. CONCLUSIONS: Serum triglyceride levels increase consistently in patients with chronic hepatitis C treated with all forms of a interferon, often to very high levels. These changes do not seem to be associated with clinical signs or complications and triglyceride levels decline while patients are still on therapy and return to normal after stopping.     

Modulation of atrial contraction by PKA and PKC during the compensated phase of eccentric cardiac hypertrophy

Abstract. Calcium homeostasis is intimately regulated by protein kinase phosphorylation cascades that are also involved in the induction and maintenance of cardiac hypertrophy. In addition, the development of cardiac hypertrophy has been associated with alteration in the activation of the adrenergic system. Therefore, we investigated the specific role of protein kinase A (PKA) and C (PKC) on cardiac muscle contractile activity in the presence and absence of adrenergic stimulation. Isolated left atrial preparations from sham– and volume overload–induced cardiac hypertrophied rats were superfused with Tyrode and electrically stimulated at 0.75 Hz. Contraction was assessed in the basal and pre–stimulated (norepinephrine, 10^–9M) states. Specific inhibitors, KT 5720 for PKA and Ro-32-0432 for PKC, were used. Peak tension development in left atria from sham–operated rats was more sensitive to PKC– than PKA–inhibition, whereas this differential sensitivity was abolished in the hypertrophied hearts. This difference was mainly due to an increase in the role of PKA in the contractile response. Developed peak tension by left atria from shunt rats was higher than that from sham rats, but when expressed to relative tissue mass, hypertrophied muscle showed weaker contraction than that from the sham group. In addition, the left atrial velocity of contraction in the sham is PKA–sensitive, while that of the shunt is PKC–sensitive. Furthermore, the velocity of relaxation shows dependency on both protein kinases, with PKC having a greater effect than PKA in the hypertrophied group. NE increased the PTD and the velocity of contraction (+dT/dt) through PKA and PKC dependent mechanisms, without affecting the velocity of relaxation (–dT/dt) in atrial muscle from sham rats. In contrast, during eccentric hypertrophy NE effectively reduced PTD as well as the –dT/dt through a PKC–dependent mechanism. The present study demonstrates that during early development of moderate eccentric cardiac hypertrophy there is: (1) a reduced specific peak tension developed due to an imbalance in the PKA and PKC activation; (2) a change in the protein kinase dependence of the velocity of contraction and relaxation from PKA to PKC with atrial hypertrophy; and (3) a negative inotropic response to adrenergic receptor stimulation. These functional responses may play a critical role in the cardiac performance during the progression of eccentric cardiac hypertrophy into the decompensated phase and heart failure.