Complementary therapy for psoriasis

The authors provide some specifications regarding the correct terminology to be applied in the field of complementary medicine, and review and comment on several complementary treatments for psoriasis. Putative psychotherapeutic equivalents are kept distinct from treatments based on the surreptitious administration of physical or pharmacologic agents. Limits on the application of psychotherapeutic techniques are discussed. Risks inherent to complementary treatments (psychological derangements, moral subjugation, physical damage, economic exploitation) are underscored. The authors plead for the application of adequate scientific criticism in complementary medicine, but warn that any approach to the practice of medicine which is not disinterested and patient oriented--as the academic one should be--will be inappropriate, misleading, or even immoral. In the authors' opinion, this could also apply to the evidence-based medicine movement (often perceived as the archenemy of alternative medicine), should this movement be influenced by economical, political, or other nonmedical factors.     

Oesophageal cancer in patients with head and neck cancers: therapeutic implications

AIM OF THE STUDY: To determine therapeutic and prognostic implications of an associated head and neck primary cancer in patients undergoing oesophagectomy for squamous cell carcinoma of the oesophagus. PATIENTS AND METHODS: Between 1982 and 2000, 868 patients with oesophageal cancer were operated in our institution, including 78 (9%) who underwent oesophagectomy for associated oesophageal and head and neck cancers; the latter was synchronous (n = 52) or anterior metachronous (n = 26). Influence of head and neck cancer on the treatment of oesophageal carcinoma was analysed retrospectively in terms of surgical therapeutic strategy and survival. RESULTS: Oesophageal resection consisted of oeso-pharyngolaryngectomy (n = 14, 17.9%), subtotal oesophagectomy (n = 62, 79.5%) and cervical oesophagectomy (n = 2, 2.6%). Radical resection (R0) was obtained in 85% of cases. Postoperative mortality rate was 5 % (4/78). Main complications were pulmonary (18% = 14/78) and anastomotic leaks (14% = 11/78), all of them cervical. Follow-up (mean = 25 +/- 27 months) was complete for all 78 patients. Five-year survival after R0 resection was 25%. Survival pronostic factors were denutrition, complete resection, and pT status of oesophageal tumor. CONCLUSION: In patients with associated carcinomas of oesophagus and head and neck, agressive treatment -including an oesophagectomy- allowed a 5-year survival rate more than 25% without increased mortality or morbidity rates, compared with patients operated on for isolated oesophageal carcinoma.     

Tetrofosmin imaging in the detection of myocardial viability in patients with previous myocardial infarction: comparison with sestamibi and tl-201 scintigraphy

BACKGROUND: Technetium 99m tetrofosmin has been introduced as a myocardial perfusion agent, providing similar results to those of thallium 201 and sestamibi in the identification of patients with coronary artery disease. No data are available comparing tetrofosmin and sestamibi imaging in the identification of reversible left ventricular (LV) dysfunction in the same patients. This study compared the results of tetrofosmin, thallium, and sestamibi single photon emission computed tomography at rest in detection of myocardial viability in patients with previous myocardial infarction. METHODS AND RESULTS: Seventeen patients with previous myocardial infarction who were undergoing coronary revascularization were studied. Echocardiography was performed at baseline and 3 months after revascularization to evaluate recovery of LV function. The optimal threshold cutoffs to separate reversible from irreversible dysfunction, as determined by receiver operating characteristic analysis, were 55% of peak activity for both tetrofosmin and sestamibi and 60% for thallium. In all asynergic segments (n = 77) analyzed, tetrofosmin uptake correlated with both sestamibi (r = 0.90, P <.0001) and thallium (r = 0.85, P <.0001) activity. The sensitivity and specificity for reversible dysfunction were, respectively, 70% and 70% for tetrofosmin, 70% and 66% for sestamibi, and 60% and 68% for thallium imaging (all P = not significant). The areas under the receiver operating characteristic curves constructed for tetrofosmin, thallium, and sestamibi activity were 0.74 +/- 0.06 (mean +/- SD), 0.75 +/- 0.06, and 0.74 +/- 0.06, respectively (all P = not significant). Concordance for detecting myocardial viability between tetrofosmin and thallium imaging was found in 67 regions (87%) (kappa = 0.74), and concordance between tetrofosmin and sestamibi imaging was found in 69 regions (90%) (kappa = 0.79). CONCLUSIONS: The diagnostic performance of quantitative rest tetrofosmin single photon emission computed tomography in predicting functional recovery after revascularization is comparable to that of both thallium and sestamibi scintigraphy in patients with myocardial infarction and chronic LV dysfunction.     

Normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney-pancreas transplantation

To evaluate the effects of kidney-pancreas transplantation on hemostatic abnormalities in uremic type 1 diabetic patients, we conducted a cross-sectional study involving 12 type 1 diabetic patients, 30 uremic type 1 diabetic patients, 27 uremic type 1 diabetic patients who had a kidney-pancreas transplant, 12 uremic type 1 diabetic patients who had a kidney-alone transplant, and 13 healthy control subjects. We evaluated platelet and clotting system. Platelets in the group of uremic type 1 diabetic patients were significantly larger than platelets in the other groups. Resting calcium levels were significantly higher in the uremic type 1 diabetic patients and uremic type 1 diabetic patients who had a kidney-alone transplant than in the type 1 diabetic patients who had a kidney-pancreas transplant and control subjects. CD41 expression was significantly reduced in platelets from the uremic type 1 diabetic patients compared with the other groups. Levels of hypercoagulability markers in the type 1 diabetic patients who had a kidney-pancreas transplant and, to a lesser extent, the uremic type 1 diabetic patients who had a kidney-alone transplant but not the uremic type 1 diabetic patients were similar to those of the control subjects. A reduction in natural anticoagulants was evident in the uremic type 1 diabetic patients, whereas near-normal values were observed in the type 1 diabetic patients who had a kidney-pancreas transplant and uremic type 1 diabetic patients who had a kidney-alone transplant. Hemostatic abnormalities were not observed in type 1 diabetic patients who had a kidney-pancreas transplant. This finding might explain the lower cardiovascular death rate observed in type 1 diabetic patients who had a kidney-pancreas transplant compared with uremic type 1 diabetic patients who had a kidney-alone transplant or uremic type 1 diabetic patients.     

Hospital use of decontaminating mats

Decontaminating mats made of several layers of adhesive sheets (water-based acrylic 6 g/m2) supplemented with a bactericidal agent (3-1 benzoisothiazolin) at a concentration of 25% were placed in the passages providing access to the operating rooms of an orthopaedic service. Contact plates containing tryptone soy agar were used to assess bacterial concentration at specific points in front of and beyond the mats. For trolley passageways two areas were defined: central and lateral paths, corresponding to the areas walked upon by the personnel pushing the trolleys and to the paths covered by the trolley wheels, respectively. In order to exclude a simple mechanical effect, a comparison of bacterial loads at defined sites beyond the mats was carried out in the presence and in the absence of decontaminating mats. Bacterial colony counts in the presence of decontaminating mats were substantially and statistically significantly reduced compared with the absence of mats. The lower mean number of colony-forming units detected at points located beyond the mats parallels this finding; this difference is also statistically significant. We thus conclude that decontaminating mats are potentially useful in decreasing micro-organism carry-over due to personnel or the passage of trolleys into areas at high risk of infection such as operating rooms.     

CD4 mimetics sensitize HIV-1-infected cells to ADCC

HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cell-mediated cytotoxicity (ADCC). HIV-1 has evolved a sophisticated mechanism to avoid exposure of ADCC-mediating Env epitopes by down-regulating CD4 and by limiting the overall amount of Env at the cell surface. Here we report that small-molecule CD4-mimetic compounds induce the CD4-bound conformation of Env, and thereby sensitize cells infected with primary HIV-1 isolates to ADCC mediated by antibodies present in sera, cervicovaginal lavages, and breast milk from HIV-1-infected individuals. Importantly, we identified one CD4 mimetic with the capacity to sensitize endogenously infected ex vivo-amplified primary CD4 T cells to ADCC killing mediated by autologous sera and effector cells. Thus, CD4 mimetics hold the promise of therapeutic utility in preventing and controlling HIV-1 infection.Worldwide, it is estimated that more than 35 million people are living with HIV. In 2013 alone, around 2.1 million people became newly infected with HIV, and 1.5 million people died from AIDS (1). Measures to prevent HIV-1 transmission are desperately needed. Prevention of HIV-1 transmission and progression likely requires approaches that can specifically target and eliminate HIV-1-infected cells. Interestingly, there is increasing evidence supporting a role of antibody (Ab)-dependent cell-mediated cytotoxicity (ADCC) in controlling HIV-1 transmission and disease progression (2–8). Analysis of the correlates of protection in the RV144 vaccine trial suggested that increased ADCC activity was linked with decreased HIV-1 acquisition (9), and Abs with potent ADCC activity were isolated from some RV144 vaccinees (10). Recent studies reported that the viral accessory proteins Nef and Vpu protect HIV-1-infected cells from anti-HIV-1 envelope (Env)-mediated ADCC responses (11–14). Importantly, we and others reported that Env in the CD4-bound conformation was preferentially targeted by ADCC-mediating Abs and sera from HIV-1-infected individuals (11, 12, 15, 16), which represent a significant proportion of anti-Env Abs elicited during natural HIV infection (11, 17). However, the vast majority of circulating HIV-1 strains worldwide express functional Nef and Vpu proteins, which limit the exposure of CD4-induced (CD4i) Env epitopes at the surface of infected cells, likely preventing ADCC responses.Theoretically, agents promoting the CD4-bound Env conformation should expose CD4i epitopes that are readily recognized by ADCC-mediating Abs and sera from infected individuals (11, 12, 15, 16, 18), resulting in the sensitization of HIV-1-infected cells to ADCC. Importantly, modulating Env conformation at the surface of HIV-1-infected cells has become feasible as a result of the availability of small CD4-mimetic compounds (CD4mc). The prototypes of such compounds, NBD-556 and NBD-557, were discovered in a screen for inhibitors of gp120-CD4 interaction (19). These small-molecule ∼337-Da compounds and recent derivatives (DMJ-I-228, JP-III-48) bind in the Phe-43 cavity (20–22), a highly conserved ∼150-ų pocket in the gp120 glycoprotein located at the interface of the inner domain, outer domain, bridging sheet, and CD4 receptor (23). CD4mc block gp120-CD4 interaction and induce thermodynamic changes in gp120 similar to those observed during CD4 or soluble CD4 (sCD4) binding (24). Accordingly, these small molecules, as well as sCD4, can promote the transition of Env to the CD4-bound conformation, thus sensitizing HIV-1 particles to neutralization by otherwise nonneutralizing CD4i Abs (17, 25). Additional strategies using scaffolded miniproteins targeting critical gp120 elements required for CD4 interaction allowed the identification of CD4 mimetics with nanomolar affinity for gp120 (26). One of these variants, M48U1, displayed remarkably potent neutralization of three HIV-1 isolates (27). Its crystal structure in complex with HIV-1 gp120 was recently solved, showing that M48U1 engages the Phe-43 cavity in a manner similar to that of CD4 (28); thus, M48U1 might induce gp120 to adopt the CD4-bound conformation and expose CD4i epitopes. Previous studies exploring the antiviral properties of CD4mc were performed on viral particles (17, 25, 27). However, whether these compounds are able to engage the large amounts of Env present at the surface of infected cells and modulate Env conformation in a way that allows exposure of ADCC-mediating epitopes is currently not known. In this study, we show that CD4mc strongly sensitize HIV-1-infected primary CD4 T cells to ADCC mediated by sera, cervicovaginal fluids, and breast milk from HIV-1-infected individuals, as well as help eliminate infected, ex vivo-expanded primary CD4 T cells from HIV-1-infected individuals. Therefore, CD4mc possess three valuable complementary antiviral properties: direct inactivation of viral particles, sensitization of viral particles to neutralization by otherwise nonneutralizing Abs, and sensitization of HIV-1-infected cells to ADCC-mediated killing.