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Sat, 01 Apr 2006
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J Cell Physiol
2006 Mar 30;
The 5(th) National Congress of the Italian Society of Virology (SIV) was attended by junior- and senior-level virologists to promote interactions and scientific collaborations among the different areas of Virology and allied sciences. The invited and selected lecturers covered the following topics: General Virology and Viral Genetics; Virus-host Interaction and Pathogenesis; Viral Oncogenesis; Viral Immunology and Vaccines; Anti-viral Therapy; Innovative Diagnostics; Viral Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata and Palù, 2004; Salata et al., 2005), a specific topic was thoroughly covered in a roundtable. This year the elected subject was "HIV: determinants of pathogenicity and clinical implications." The final program and the abstract book can be found at the web site http://www.siv-virologia.it. This report summarizes the lessons learned from the plenary lectures and the selected oral presentations of the 2005 meeting. J. Cell. Physiol. (c) 2006 Wiley-Liss, Inc.
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Crim Behav Ment Health
2006 Mar 30; 14(4): 263-279
BACKGROUND: Forensic psychiatrists aim to reduce the risk of reoffending through treatment. With few exceptions, research evidence tends to favour risk assessment aids reliant on fixed historical rather than clinical data, but transparency in the making of clinical judgements is lacking. AIMS: To evaluate further a clinically derived 47-item dynamic risk assessment checklist; specifically to test first whether it has a meaningful dimensional structure and, second, the extent to which items and underlying dimensions are associated with a separate, direct clinical judgement of risk of reoffending. METHODS: Data sets from four previous studies on the reliability and validity of the Clinical Inventory of Dynamic Reoffending Risk Indicators (CIDRRI) were merged, yielding 370 cases. The resulting data set was analysed using principal axis (common) factor analysis, with orthogonal (varimax) rotation. In addition, receiver operating characteristic (ROC) curves were calculated. RESULTS: The model of best fit depended on treatment stage; for those in residential treatment it was a six-factor model (responsibility, self-reliance, antisocial/narcissistic traits, treatment compliance, goal attainment and avoidance); for those back in the community a five-actor model in which, effectively, the compliance and goal attainment factors became one, provided a better fit. These dimensions and some individual scale items were associated with clinical judgement of risk of reoffending. CONCLUSIONS AND CLINICAL IMPLICATIONS: This study provides evidence that the CIDRRI is an adequate operationalization of underpinnings of clinical risk assessment, and that these underpinnings are part of meaningful higher-order dimensions. The CIDRRI is a viable instrument for clinical use, taking only 15 minutes to complete and identifying dynamic risk factors, the validity of which needs to be further established. Copyright (c) 2004 Whurr Publishers Ltd.
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Clin Infect Dis
2006 Apr 15; 42(8): 1189-96
Background. Effective therapeutic drug monitoring for antiretrovirals requires a better understanding of intraindividual variability in pharmacokinetics.Methods. We determined concentrations of human immunodeficiency virus (HIV) protease and nonnucleoside reverse-transcriptase inhibitors for 10 patients with undetectable plasma HIV RNA levels who had been receiving stable regimens for >/=11 months. Plasma samples were collected at the same time of day 3 times per week for up to 4 months. Patients were instructed to take their antiretrovirals at the same time every day. Plasma protease and nonnucleoside reverse-transcriptase inhibitor concentrations were determined using high-performance liquid chromatographic methods. Pharmacokinetic variability was expressed as intraindividual percentage coefficient of variation (ICV), which was calculated as the patient's standard deviation divided by the mean drug concentration for that patient.Results. ICV was determined for 6 drugs for 10 patients, for a total of 17 different patient-drug combinations, using 600 total samples. ICV was unexpectedly high for most patients who were receiving protease inhibitors (ICVs for individual patients taking lopinavir/ritonavir were 24%, 33%, 51%, and 92%; for patients taking nelfinavir/M8 metabolite, they were 30%/44% and 39%/54%; for patients taking ritonavir, they were 34% and 43%; for patients taking saquinavir, they were 52% and 55%). ICVs for patients receiving nonnucleoside reverse-transcriptase inhibitors were lower (for patients receiving efavirenz, they were 7%, 13%, 29%, and 51%; for a patient receiving nevirapine, it was 25%). The median ICV for all patients receiving protease inhibitors (n = 12) was 43.5%, and for all patients receiving nonnucleoside reverse-transcriptase inhibitors (n = 5), the median ICV was 25%.Conclusions. Intraindividual variability in concentrations of antiretrovirals was surprisingly high in virologically suppressed patients. Possible contributors include food effects, concomitant use of prescription and herbal medications, assay variability, or medication timing, which was assessed by self-report. High intraindividual pharmacokinetic variability may limit the utility of single measurements in therapeutic drug monitoring for some antiretroviral agents.
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J Trop Pediatr
2006 Mar 29;
Aim: To determine whether vaginal delivery along with antiretroviral therapy and avoidance of breast feeding is safe in preventing mother to child transmission (MTCT) of HIV.Setting: Pediatric & Perinatal HIV clinic, B.J. Wadia Hospital for children, Mumbai.Study design: Retrospective analysis.Methods and materials: 222 HIV-infected pregnant women were treated with zidovudine from 14 weeks of gestation onwards. 174 women underwent an elective caesarian section whereas 48 women delivered spontaneously vaginally. All infants were treated with zidovudine for 6 weeks and breast feeding was withheld. The HIV status of infants was determined at 18 months by ELISA test.Results: Of the 174 infants delivered through LSCS delivery, two were HIV infected whereas 172 (98.9%) were HIV uninfected. Of the 48 infants delivered vaginally, 47 (97.9%) were HIV negative and one child was HIV infected. Thus, elective caesarean section was not statistically better as compared to vaginal delivery ( p = 0.8696) suggesting that vaginal delivery was as effective as caesarean section for prevention of MTCT of HIV when added with antiretroviral therapy and no breast feeding.Conclusion: Vaginal delivery along with antiretroviral therapy in mother and baby and avoidance of breast feeding is equivalent to that of an elective LSCS delivery for prevention of mother-to-child transmission of HIV. Surgical intervention may thus not be required in these women.
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Rehabilitation (Stuttg)
2006 Apr; 45(2): 102-9
An inpatient rehabilitation programme for HIV-infected patients is described. Since the early nineties some 1200 patients with HIV infection have been treated in our internal and orthopaedic rehabilitation clinic. Beside internal and orthopaedic diagnostics, supporting compliance with antiretroviral therapy, motivating the patients for regular moderate exercises and specific nutritional counselling are major issues of the programme. From the psychological point of view, the patients are offered to aquire relaxation and stress coping techniques, to take part in non-smoking courses and to use individual psychological counselling in case of depression or panic. In addition, all HIV-infected patients are offered individual advice on their disease and necessary changes in lifestyle. Finally, the programme includes social medical evaluation and counselling. As the majority of the patients are still working or are of working age, evaluating the capacity for work and potential introduction of occupational rehabilitation measures are prominent. Almost 70 percent of the HIV-infected patients who had been treated in our clinic over the last few years were fully capable of returning to their previous occupation. Our experiences demonstrate that statements such as rehabilitation of AIDS patients being useless because of its missing prospects of success, are not up-to-date any longer. Since introduction of combination antiretroviral therapy many patients with HIV infection are able to return to their previous occupation if they receive the necessary medical und psychosocial support.
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Science
2006 Mar 31; 311(5769): 1921-4
Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) is the causative agent of Kaposi's sarcoma and other lymphoproliferative syndromes often associated with HIV/AIDS. Functional complementary DNA selection for a receptor mediating KSHV cell fusion identified xCT, the 12-transmembrane light chain of the human cystine/glutamate exchange transporter system x-c. Expression of recombinant xCT rendered otherwise not susceptible target cells permissive for both KSHV cell fusion and virion entry. Antibodies against xCT blocked KSHV fusion and entry with naturally permissive target cells. KSHV target cell permissiveness correlated closely with endogenous expression of xCT messenger RNA and protein in diverse human and nonhuman cell types.
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Facial Plast Surg
2005 Nov; 21(4): 296-303
Techniques and concepts for treatment of the aging neck have been evolving since the late 1960s and rely on two-dimensional anterior approximation with lateral imbrication of the platysma with or without submental fat reduction, However, the medial approximation can sometimes give a "boxy" appearance to the anterior neck, especially if anterior shifting of the platysma recurs after platysmaplasty with laxity redeveloping in this midline location. The "purse-string" platysmaplasty (PSP) is a new concept in neck contouring that facilitates an enhanced definition for the cervicomandibular transition to better simulate the well-defined contour of this transition that is present in youth. It aids in the contouring of difficult poorly defined necks and in male patients. The PSP adds a "third dimension" to neck recontouring by invaginating the platysma with a plication suture and pexing the platysma, without incising it, to deeper neck fascia with a technique that adds support and definition to the neck contour. The PSP can be performed in patients undergoing a full rhytidectomy as well as in individuals having isolated neck rejuvenation. The PSP is especially helpful in rejuvenating the male lower face and neck because of the relatively heavier deeper structures of the male neck and the need to enhance definition along the jawline.
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Clin Infect Dis
2006 Apr 15; 42(8): 1102-10
Background. We are developing a heterologous prime-boost vaccine strategy against malaria. This approach uses sequential immunization with different vectors to deliver a common preerythrocytic malaria antigen. Preliminary evidence of efficacy and safety has been previously documented in studies from an area where malaria is nonendemic. Additional safety data from an area where malaria is endemic are now required before larger-scale studies are undertaken to determine the efficacy of this vaccine strategy in the field. Other modified vaccinia virus Ankara (MVA) recombinants and prime-boost immunizations are being developed as vaccines against human immunodeficiency virus (HIV) infection, tuberculosis, and cancer, and MVA is a candidate attenuated smallpox vaccine.Methods. Candidate vaccines against malaria were intradermally administered to 73 adults (7 of whom were HIV positive) and 22 children in Kenya. These vaccines used the attenuated fowlpox strain FP9 and the MVA recombinant for either of 2 preerythrocytic malaria antigens, multiple preerythrocytic-stage epitopes joined with the preerythrocytic-stage antigen TRAP (ME-TRAP) and the circumsporozoite protein (CS). Adverse events were recorded.Results. Reactogenicity was mild. MVA caused less frequent and less severe cutaneous reaction if given after FP9 priming. Half doses reduced the frequency and the severity of systemic reactogenicity, and particular vaccine lots were associated with different reactogenicities. Unexpectedly, prior immunity to the ME-TRAP antigen appeared to be protective against local reactions after immunization.Conclusions. Where the final intention is to use MVA after FP9 priming, previous testing of MVA alone overestimates reactogenicity. These recombinant vectors appear to be safe and suitable for use in larger-scale studies of children in Africa and of HIV-positive individuals.
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Zentralbl Chir
2006 Apr; 131(S 1): 24-28
V.A.C.(R)-therapy has improved the treatment of extended pressure sores, because of its beneficial effect on the wound surface and the safe microbial barrier. Definitive reconstructive surgery can be performed earlier. Using modern aids fixation of the device will be possible even in difficult locations as the perianal area. This is important for immobile and multimorbid patients. On the other hand, this area still shows limitations of the method. In recurrent cases it is difficult to use classical methods of reconstruction. Long-term-treatment is necessary, which is economically difficult. It is important for hospitals to cooperate with specialised wound therapeutics so that these patients can be dismissed earlier. This may allow reconstructive procedures, even if this takes several hospital stays over a long period of time.
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J Leukoc Biol
2006 Mar 30;
Acute and chronic alcohol abuse impairs various functions of the immune system and thus, has been implicated as a cofactor in the immunopathogenesis of human immunodeficiency virus (HIV) disease progression. We determined whether naltrexone, an opioid receptor antagonist widely used in the treatment of alcoholism, inhibits alcohol-mediated enhancement of HIV infection of T cells. Alcohol enhanced HIV infection of peripheral blood lymphocytes (PBL) and a human lymphoid cell line (CEMX174). Alcohol increased HIV X4 envelope (Env), not murine leukemia virus Env-pseudotyped infection of CEMX174 cells. Naltrexone antagonized the enhancing effect of alcohol on HIV infection of PBL and CEMX174 cells. The specific micro-opioid receptor antagonist, Cys(2), Tyr(3), Arg(5), Pen(7) (CTAP) amide, also blocked the enhancing effect of alcohol on HIV infection. Investigation of the underlying mechanism for the alcohol action showed that alcohol significantly increased endogenous beta-endorphin production and induced micro-opioid receptor mRNA expression in PBL and CEMX174 cells. The role of beta-endorphin in alcohol-mediated enhancement of HIV infection was indicated by the observations that naltrexone and CTAP antagonized ether alcohol- or exogenous beta-endorphin-mediated enhancement of HIV infection. These findings suggest a biological mechanism for the potential therapeutic benefit of naltrexone in treating HIV-infected alcoholics.
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Gynecol Obstet Fertil
2006 Mar 27;
OBJECTIVE: Evaluate the mode of delivery of HIV-infected women and the risk of mother-to-child transmission. PATIENTS AND METHODS: A retrospective study conducted on HIV-infected women who delivered at the maternity ward of Bichat Hospital in Paris between 1st January 2000 and 31(st) December 2004. Pregnancy care, antiretroviral therapy, decision of the mode of delivery and neonate treatment were conformable to the French recommendations. RESULTS: The analysis was performed on 332 cases out of 358 pregnancies followed during this period. 75% received a Highly Active Anti Retroviral Therapy (HAART), 24% an AZT monotherapy and 1% did not receive any antiretroviral treatment. Plasmatic HIV viral load was under the level of detectability (50 copies/ml) for 64,6% of women under HAART and 28,7% of women under AZT monotherapy. Only 31,7% of women under HAART delivered vaginally. 44,7% of women under HAART with undetectable viral load at the moment of delivery delivered vaginally. 59,5% of women who were allowed to deliver vaginally had finally a vaginal delivery. 332 women gave birth to 341 babies with 9 twin pregnancies and one still-birth at 22 WA. Out of these 340 babies, 3 babies whose mother received HAART were HIV infected (2 in utero and 1 per-partum). DISCUSSION AND CONCLUSION: The reasons why only one third of HIV-infected women could deliver vaginally in this study are primarily the persistence of a detectable HIV viral load under HAART. Women's choice of the mode of delivery comes next, which depends on the quality of the counselling about the benefits and risks of the cesarean section in the context of HIV infection. The third reason is obstetrical contra indications to vaginal delivery in the context of HIV infection. In the future, it is possible to reduce the incidence of cesarean section in HIV-infected women by elevating the level of HIV plasmatic viral load which allowed vaginal delivery (1000 copies/ml), by improving the observance to antiretroviral treatment, by adaptating antiretroviral medications posology using determination of serum protease inhibitors concentration and by modifying obstetrical management with less restrictive contra indications to vaginal delivery. However the impact of prophylactic cesarean section when plasmatic HIV viral load is undetectable must still be evaluated.
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J Psychopharmacol
2006 May; 20(3): 425-31
The drug ecstasy has appetite suppressant and exercise promoting effects that may appeal to young women who are concerned about weight and body image. This study therefore aimed to determine whether young women who use ecstasy differ from those who do not use this drug in concerns about eating and weight, and in beliefs about how these are affected by recreational drugs. One hundred and thirty young women, all cigarette smokers, were recruited; 73 who used ecstasy were compared with 57 who did not. All were assessed on Garner's (1991) Eating Disorder Inventory (EDI-2), body mass index (BMI), depression and beliefs about the effects of different drugs on appetite, exercise and weight. The two groups did not differ on number of cigarettes smoked per day, depression scores, current BMI, lowest achieved BMI or ideal BMI. Ecstasy users had significantly higher scores than controls on four of the 11 sub-scales of the EDI: bulimia, impulse dysregulation, social insecurity and interpersonal distrust. For ecstasy users, scores on all four scales correlated positively with frequency of ecstasy use. However there were no group differences in 'drive for thinness' or 'body dissatisfaction' which may suggest that differences on other factors are related more to use of club drugs than to any specific eating pathology. Ecstasy users were more likely than controls to agree that ecstasy aids weight loss and that they exercise more when they use drugs. However, our findings indicated that women are not using ecstasy as a deliberate means of weight control.
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Indian J Med Res
2006 Feb; 123(2): 139-44
BACKGROUND & OBJECTIVE: Mycobacterium avium has emerged as a major opportunistic pathogen, infecting nearly 50 per cent of HIV/AIDS patients in the western world. There is no report from India regarding the typing profile of M. avium, a potential pathogen, the present study was undertaken to assess the genotypic diversity of Indian M. avium isolates of human origin. METHODS: A total of 65 biochemically identified M. avium isolates from sputum samples of patients with chronic pulmonary illness were subjected to IS1245 based restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) typing. RESULTS: IS1245 insertion sequence based RFLP demonstrated polymorphism in 84.6 per cent isolates, while 15.4 per cent isolates did not hybridize on Southern blot and therefore were RFLP negative. Among the 55 RFLP positive isolates, 8 showed 1-3 bands, 19 had bands ranging between 4-9, and 28 isolates had >10 bands each. Although the isolates could be clubbed on the basis of number of bands, the banding profile was highly polymorphic. Among the 55 isolates typeable by RFLP, four clusters and 40 unique types of polymorphism were observed. Application of IS1245 based PCR typing on the same isolates showed that 87.7 per cent isolates were typeable. Interestingly the 10 isolates that were not typeable by IS1245 RFLP were typeable by IS1245 based PCR typing. Among the 57 PCR typed isolates a cluster of 14 isolates with identical 3-banded pattern was observed. Notably, 5 of the ten IS1245 RFLP negative isolates were within this cluster. INTERPRETATION & CONCLUSION: Our results demonstrated that M. avium isolates from India were highly polymorphic with remarkable genetic diversity and heterogeneous RFLP profile. We observed that 47 per cent (n=27) isolates had RFLP profile suggestive of bird and animal origin indicating a strong association with the environment. By applying two typing methods based on IS1245 on the isolates 100 per cent typeability could be achieved.
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Theriogenology
2006 Mar 28;
Holding immature oocytes before the onset of maturation simplifies oocyte transport and aids in scheduling later manipulations. We report here a method for holding equine oocytes in the absence of meiotic inhibitors. In Experiment 1, immature oocytes with expanded cumuli were cultured at 38.2 degrees C in medium containing cycloheximide, or were held at room-temperature in M199 with Hanks' salts, for 16-18h before maturation. Control oocytes were matured immediately after recovery. Oocytes were fertilized by intracytoplasmic sperm injection and cultured for 4d. Embryo development was not different among treatments. In Experiment 2, oocytes were treated as in Experiment 1, but embryos were cultured for 7.5d. Blastocyst development was significantly lower in the cycloheximide-treated group than in controls (7% versus 30%) with the room-temperature group intermediate (16%). In Experiment 3, oocytes were cultured at 38.2 degrees C in medium containing roscovitine, or were held at room temperature in sealed glass vials in a mixture of 40% M199 with Earle's salts, 40% M199 with Hanks' salts, and 20% FBS (EH treatment) for 16-18h, before maturation, sperm injection, and embryo culture for 7.5d. Blastocyst development of oocytes in the EH treatment was significantly higher than that for roscovitine-treated oocytes (34% versus 12%), but not significantly different from that for controls (25%). Oocytes in the EH treatment did not mature during holding (70% germinal vesicle stage after 18h holding). Whereas culture with cycloheximide or roscovitine of equine oocytes with expanded cumuli reduced subsequent blastocyst formation, these oocytes could be held in a modified M199 at room temperature overnight without adverse affecting meiotic or developmental competence.
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Clin Infect Dis
2006 Apr 15; 42(8): 1179-86
Background. Oropharyngeal candidiasis is the most common opportunistic infection among persons infected with human immunodeficiency virus (HIV). Use of some agents is hampered by lack of efficacy, emergence of resistance, adverse events, and need for intravenous administration. Posaconazole is an extended-spectrum triazole with potent in vitro activity against Candida species, including Candida albicans, Candida glabrata, and Candida krusei (including fluconazole-resistant strains).Methods. This multicenter, randomized, evaluator-blinded study of subjects with HIV infection and oropharyngeal candidiasis compared efficacy of posaconazole with that of fluconazole. Subjects received either 200 mg of posaconazole or fluconazole oral suspension on day 1, followed by 100 mg/day for 13 days. The primary study end point--clinical success (cure or improvement) on day 14--was evaluated for 329 subjects. Durability of clinical success was evaluated on day 42.Results. Three hundred fifty subjects received posaconazole (n = 178) or fluconazole (n = 172). Clinical success occurred in 155 (91.7%) of 169 posaconazole recipients and in 148 (92.5%) of 160 fluconazole recipients (95% confidence interval, -6.61% to 5.04%), indicating that posaconazole was not inferior to fluconazole. On day 14, mycological success was 68% in both arms, but by day 42, significantly more posaconazole recipients than fluconazole recipients continued to have mycological success (40.6% vs. 26.4%; P=.038). Fewer posaconazole recipients than fluconazole recipients experienced clinical relapse (31.5% vs. 38.2%). Adverse events were similar between treatment arms.Conclusions. Results demonstrate that posaconazole was as effective as fluconazole in producing a successful clinical outcome. However, posaconazole was more effective in sustaining clinical success after treatment was stopped.
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Vaccine
2006 Mar 20;
Present study aims to enhance the efficacy of liposomes as an adjuvant by steric protection and strengthen the path of vaccine research. PEG grafted liposomes carrying epitopes on their surface showed enhanced adjuvanticity than liposomes carrying epitopes for elicitation and prolongation of immune response to an antigenic epitope of gp41, a transmembrane protein of HIV-1. The multiples of epitope were incorporated onto the surface of liposomes by conjugating them with phosphatidylethanolamine that was used in the formulation of liposomes at an optimized ratio. Furthermore, the liposomes carrying epitopes on their surface were sterically protected by shielding with methoxy-poly(ethylene glycol), mass 20kDa. Methoxy-poly(ethylene glycol) was activated to its electrophilic N-succinimide carbonate derivative, methoxy-poly(ethylene glycol)-N-succinimide carbonate, that formed a urethane linkage with the amino group of phosphatidylethanolamine. The epitope was covalently coupled to phosphatidylethanolamine through an amide bond between the -COOH group of the epitope and -NH(2) group of phosphatidylethanolamine under the catalysis of 1-ethyl-3-(3-dimethylaminopropy-1)-carbodiimide. PEG grafted epitopes carrying liposomes showed about two times higher immune response and prolonged persistence of antibodies than that of liposomes carrying epitopes without PEG moieties.
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