CD8 T lymphocytes do not express cytotoxic proteins in coronary artery aneurysms in acute Kawasaki disease

Coronary arterial inflammation in acute Kawasaki disease (KD) is characterized by transmural infiltration of CD8 T lymphocytes, suggesting that CD8 T lymphocyte cytotoxic activity may be important in the pathogenesis of coronary arterial damage in acute KD. We performed immunohistochemistry for the cytotoxic proteins perforin and granzyme B on paraffin-embedded, formalin-fixed coronary artery aneurysm tissue from 6 children who died in the acute stage of KD. Neither perforin nor granzyme B was detected in the KD coronary aneurysm wall. We speculate that the etiologic agent of KD interferes with expression of these cytotoxic proteins by CD8 T lymphocytes, prolonging inflammation in the arterial wall and leading to coronary artery aneurysm formation.     

Amantadine in chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare genetically determined immunodeficiency. Neutrophils from CGD patients show a defective killing of phagocytosed fungi and bacteria, due not only to an impairment in oxidative burst, but also to absence of normal pH value within phagocytic vacuole following phagocytosis. Because a weak base such as amantadine could potentially reverse these pH abnormalities, the authors used this drug to treat 2 CGD patients. They observed modifications of both phagosomal pH and killing activity on their neutrophils compared to those of healthy controls. Since the drug has been employed, the patients have not developed new infections, suggesting a role of amantadine as a part of CGD prophylactic regimen. These results suggest the opportunity of testing the drug in larger studies.     

Adolescents and sexually transmitted infections: knowledge and behaviour in Italy

OBJECTIVE: Sexually transmitted infections (STI) among adolescents continue to be an important public health problem for many industrialized and developing countries. This study evaluated knowledge and behaviour in adolescents regarding prevention of STI. METHODS: Information was obtained by using self-reported questionnaire from a random sample of 644 undergraduate students at university and at public high schools aged 14-20 years in Catanzaro (Italy). RESULTS: Only 14.2% of respondents knew about the main STI and that they can be transmitted through sexual intercourse with HIV seropositive partners; this knowledge was significantly higher among adolescents who had had a higher number of sexual partners in their lifetime and who had received information from physicians about STI. A total of 33.8% reported having had sexual intercourse at least once and the mean age at first intercourse was 16 years. Older males and adolescents with employed mothers were more likely to have reported having had a sexual experience. The prevalence of using condoms every time during sexual intercourse was 51.8% and such behaviour was more likely in younger adolescents and males. The prevalence of condom use on the last occasion of sex was 71.9%. Younger adolescents, those with a higher perception of the risk of contracting STI and those with lesser knowledge about STI were independent predictors for using condoms. The mean total score of the respondents' perception of a risk of contracting STI was 5.8. CONCLUSIONS: Evidence to develop and implement strategies with the hope of improving adolescents' level of knowledge and reducing unsafe sexual practices.     

Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia

OBJECTIVE: Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain. Symptoms of orthostatic intolerance may also be present, suggesting underlying abnormalities of cardiovascular neural regulation. We tested the hypothesis that FM is characterized by sympathetic overactivity and alterations in cardiovascular autonomic response to gravitational stimulus. METHODS: Sixteen patients with primary FM and 16 healthy controls underwent electrocardiography examination, finger blood pressure, respiration, and muscle sympathetic nerve activity (MSNA) recordings at rest and during stepwise tilt test, up to 75 degrees . The autonomic profile was assessed by MSNA, plasma catecholamine, and spectral indices of cardiac sympathetic (LFRR in normalized units, NU) and vagal (HFRR both in absolute and NU) modulation and of sympathetic vasomotor control (LFSAP) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variability. Arterial baroreflex function was evaluated by the SAP/RR spontaneous-sequences technique, the index a, and the gain of MSNA/diastolic pressure relationship during stepwise tilt test. RESULTS: At rest, patients showed higher values of heart rate, MSNA, LFRR NU, LF/HF, LFSAP, and reduced HFRR than controls. During tilt test, lack of increase of MSNA, less decrease of HFRR, and excessive rate (44%) of syncope were found in patients, suggesting reduced capability to enhance the sympathetic activity to vessels and withdraw the vagal modulation to sino-atrial node. Baroreflex function was similar in both groups. CONCLUSION: Patients with FM have an overall enhancement of cardiovascular sympathetic activity while recumbent. Lack of increased sympathetic discharge to vessels and decreased cardiac vagal activity characterize their autonomic profile during tilt test, and might account for the excessive rate of syncope.     

Lack of receptor activator of nuclear factor-kB ligand (RANKL) expression and functional production by human multiple myeloma cells

The direct expression and production of the critical osteoclastogenic factor, the receptor activator of NF-kB ligand (RANKL), is a matter of controversy. In this study we definitively demonstrate by both qualitative and quantitative polymerase chain reaction analysis that human myeloma cells do not express significant levels of RANKL mRNA or produce RANKL able to stimulate osteoclast formation.     

Efficacy of bortezomib therapy for extramedullary relapse of myeloma after autologous and non-myeloablative allogeneic transplantation

We report the successful use of bortezomib to treat a patient with multiple myeloma (MM) who had extramedullary relapse (paraspinal and thoracic masses and multiple cranial nerve palsy) after autologous and non-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT).     

Left ventricular assist device implantation in a patient with congenitally corrected transposition of the great arteries

Congenitally corrected transposition of the great arteries (ccTGA) is a rare anomaly characterized by atrioventricular and ventriculo-arterial discordance and several other malformations that eventually lead to heart failure. We describe the case of a 53-year-old woman with ccTGA and aortic insufficiency who was a candidate for heart transplantation due to end-stage congestive heart failure. Her condition deteriorated before a suitable donor heart could be found; therefore, we placed a left ventricular assist device in the right (systemic) ventricle. Concomitantly, we removed the aortic (systemic) valve, closed the aortic annulus with a bovine pericardial patch, and repaired the mitral valve. The patient recovered uneventfully and was discharged from the hospital 2 months postoperatively. She underwent cardiac transplantation approximately 6 months later and continued to do well after 18 months.     

Increase in TNF-alpha and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

We find that CD11c(+) cells with many markers of dendritic cells (DCs) are a major cell type in the skin lesions of psoriasis. These CD11c(+) cells, which are evident in both epidermis and dermis, are the sites for the expression of two mediators of inflammation, inducible nitric oxide synthase (iNOS) and TNF-alpha in diseased skin. These cells express HLA-DR, CD40, and CD86, lack the Langerin and CD14 markers of Langerhans cells and monocytes, respectively, and to a significant extent express the DC maturation markers DC-LAMP and CD83. Treatment of psoriasis with efalizumab (anti-CD11a, Raptiva) strongly reduces infiltration by these DCs in patients responding to this agent. Disease activity after therapy was more related to DC infiltrates and iNOS mRNA levels than T cell infiltrates, and CD11c(+) cells responded more quickly to therapy than epidermal keratinocytes. Our results suggest that a type of DC, which resembles murine "Tip-DCs" that can accumulate during infection, has proinflammatory effects in psoriasis through nitric oxide and TNF-alpha production, and can be an important target for suppressive therapies.     

Teaching personal awareness

Educators rarely consider the attitudes that determine whether a learner will use the clinical skills we teach. Nevertheless, many learners and practitioners exhibit negative attitudes that can impede the use of patient-centered skills, leading to an isolated focus upon disease and impairing the provider-patient relationship. The problem is compounded because these attitudes often are incompletely recognized by learners and therefore are difficult to change without help. We present a research-based method for teaching personal awareness of unrecognized and often harmful attitudes. We propose that primary care clinicians without mental health training can follow this method to teach students, residents, faculty, and practitioners. Such teachers/mentors need to possess an abiding interest in the personal dimension, patience with a slowly evolving process of awareness, and the ability to establish strong, ongoing relationships with learners. Personal awareness teaching may occur during instruction in basic interviewing skills but works best if systematically incorporated throughout training.