Fully synthetic carbohydrate-based vaccines in biochemically relapsed prostate cancer: clinical trial results with alpha-N-acetylgalactosamine-O-serine/threonine conjugate vaccine.

PURPOSE: We report the synthesis of a mucin-related O-linked glycopeptide, alpha-N-acetylgalactosamine-O-serine/threonine (Tn), which is highly simplistic in its structure and can induce a relevant humoral response when given in a trimer or clustered (c) formation. We tested for an antitumor effect, in the form of a change in the posttreatment versus pretreatment prostate-specific antigen (PSA) slopes, that might serve as a surrogate for effectiveness of vaccines in delaying the time to radiographic progression. METHODS: We compared the antibody response to immunization with two conjugates, Tn(c)-keyhole limpet hemocyanin (KLH) and Tn(c)-palmitic acid (PAM) with the saponin immunologic adjuvant QS21, in a phase I clinical trial in patients with biochemically relapsed prostate cancer. Patients received Tn(c)-KLH vaccine containing either 3, 7, or 15 microg of Tn(c) per vaccination. Ten patients received 100 microg of Tn(c)-PAM. QS21 was included in all vaccines. Five vaccinations were administered subcutaneously during 26 weeks with an additional booster vaccine at week 50. RESULTS: Tn(c), when given with the carrier molecule KLH and QS21, stimulated the production of high-titer immunoglobulin M (IgM) and IgG antibodies. Inferior antibody responses were seen with T(c)-PAM. There was no evidence of enhanced immunogenicity with increasing doses of vaccine. An antitumor effect in the form of a decline in posttreatment versus pretreatment PSA slopes was also observed. CONCLUSION: A safe synthetic conjugate vaccine in a trimer formation was developed that can break immunologic tolerance by inducing specific humoral responses. It seemed to affect the biochemical progression of the disease as determined by a change in PSA log slope.     

Human immunodeficiency virus case detection and antiretroviral therapy enrollment among children below and above 18 months old: A comparative analysis from Cameroon

While pediatric human immunodeficiency virus (HIV) testing has been more focused on children below 18 months through prevention of mother to child transmission of HIV (PMTCT), the yield of this approach remains unclear comparatively to testing children above 18 months through routine provider-initiated testing and counselling (PITC). This study aimed at assessing and comparing the HIV case detection and antiretroviral therapy (ART) enrolment among children below and above 18 months of age in Cameroon. This information is required to guide the investments in HIV testing among children and adolescents.We conducted a cross-sectional study where we invited parents visiting or receiving HIV care in 3 hospitals to have their children tested for HIV. HIV testing was done using polymerase chain reaction (PCR) and antibody rapid tests for children <18 months and those ≥18 months, respectively. We compared HIV case detection and ART initiation between the 2 subgroups of children and this using Chi-square test at 5% significant level.A total of 4079 children aged 6 weeks to 15 years were included in the analysis. Compared with children <18 months, children group ≥18 months was 4-fold higher among those who enrolled in the study (80.3% vs 19.7%, P < .001); 3.5-fold higher among those who tested for HIV (77.6% vs 22.4%, P < .001); 6-fold higher among those who tested HIV+ (85.7% vs 14.3%, P = .24), and 11-fold higher among those who enrolled on ART (91.7% vs 8.3%, P = .02).Our results show that 4 out of 5 children who tested HIV+ and over 90% of ART enrolled cases were children ≥18 months. Thus, while rolling out PCR HIV testing technology for neonates and infants, committing adequate and proportionate resources in antibody rapid testing for older children is a sine quo none condition to achieve an acquired immunodeficiency syndrome (AIDS)-free generation.     

Antibiotic therapy in surgery of the Colon: Rationale and application

Summary Although intestinal antiseptics do have relative dangers, and although only 7 of 35 different intestinal antiseptics can be recommended for general use, the value of antibiotics in surgery of the colon has been experimentally demonstrated in protection of a colon anastomosis.Based upon clinical studies of 559 patients prepared for surgery with kanamycin, 79 who received postoperative intraluminal kanamycin, and 360 who received intraperitoneal antibiotic therapy at operation for some form of peritonitis, judicious use of antibiotics in conjunction with colon surgery is highly recommended.Presented at a postgraduate course, Advances in Gastroenterology—Enterocolonic Disease and Dysfunction (Oct. 22–24, 1964), sponsored by Louisiana State University School of Medicine, New Orleans, La.Supported in part by Grants Al-01600 and Al-00524 from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, U. S. Public Health Service.     

Stereospecific cis- and trans-ring fusions arising from common intermediates

Highly concise and stereospecific routes to cis and trans fusion, carrying various functionality at one of the bridgehead carbons, have been accomplished.Our group has been studying the synthetic utility of the Diels–Alder (DA) reaction of the parent cyclobutenone, 2 (1). Recently reported results demonstrate that 2 is a highly reactive, endo-selective dienophile (Fig. 1, Eq. 1) (2). We have also developed a series of intramolecular Diels–Alder (IMDA) reactions, wherein the cyclobutenone component is tethered to various conjugated dienes (compare 4); cycloaddition of these substrates delivers adducts of the type 5, which can be readily converted to trans-fused systems bearing iso-DA patterns (Fig. 1, Eq. 2, 5→6) (3). Additionally, we have described the synthesis and DA cycloaddition of an even more powerful dienophile, 2-bromocyclobutenone (Fig. 1, Eq. 3, 7) (4). The direct adducts of this [4+2] reaction (compare 8) are readily converted to norcarane carboxylic acids (9) through exposure to hydroxide base. The research described herein was initially focused on efforts to add carbon-based nucleophiles to DA cycloadducts of the type 8. It might well have been expected that such reactions would give rise to products such as 10, wherein a ketone is appended to the junction of the norcarane system (Fig. 1, Eq. 4).Open in a separate windowFig. 1.Expanding the scope of the Diels–Alder reaction.     

First-night effect in the chronic fatigue syndrome

Since the magnitude of the first-night effect has been shown to be a function of medical conditions and of settings in which polysomnographies are performed, it is essential to evaluate the habituation phenomenon in each case in order to determine the optimal recording methodology. A first-night effect was evidenced in certain cases of chronic fatigue syndrome, but not in others. To clarify this issue, a large group of patients with chronic fatigue syndrome who had no primary sleep disorders were selected and recorded for two consecutive nights in a hospital sleep unit. Several parameters, frequently associated with the first-night effect, were found to be influenced by the recording methodology: Total Sleep Time, Sleep Efficiency, Sleep Efficiency minus Sleep Onset, Sleep Onset Latency, Wake Time, Slow Wave Sleep, Rapid Eye Movement Sleep, Rapid Eye Movement Sleep Latency and Number of Sleep Cycles. Bland and Altman plots determined that the difference scores between the nights included a systematic bias linked to the order of recordings (first-night effect). Factorial analysis grouped the difference scores into three factors. No significant difference was observed between patients with generalized anxiety comorbidity and those with no psychiatric comorbidity, or between those with and without psychiatric comorbidity. Chronic fatigue syndrome must thus be added on the list of conditions where a clinically significant habituation effect takes place.     

Impaired emotional facial expression recognition in alcoholics,opiate dependence subjects,methadone maintained subjects and mixed alcohol-opiate antecedents subjects compared with normal controls

The present study aims to explore whether an impairment in emotional facial expressions (EFE) decoding is specific to alcoholism compared with opiate dependence. An EFE decoding test consisting of 16 photographs of EFE portraying happiness, anger, sadness and disgust was administered to five different groups of 30 subjects each: recently detoxified alcoholics (RA); opiate addicts under methadone maintenance treatment (OM); detoxified opiate addicts (OA); detoxified subjects with both alcohol and opiate dependence antecedents (DAO); and normal controls (NC). Repeated measures analysis of variance using a multivariate approach was conducted on EFE decoding accuracy scores with group as the between-subjects factor. Accuracy scores were significantly lower in RA and DAO than in OM and OA, which had significantly lower scores than NC. Low accuracy scores in RA and DAO confirm previous results indicating that alcoholism is associated with impaired EFE recognition. Results in OM and OA indicate that opiate dependence is also associated with an impaired EFE decoding but less than in alcoholism. Alcohol and opiate chronic consumption could both exercise a deleterious effect on EFE-decoding brain function, alcohol having the most severe impact. Alternatively, EFE-decoding problems could be present before the development of alcohol and opiate dependence, with an additional effect of chronic alcohol consumption on EFE decoding. In this context, EFE-decoding impairment could reflect a more general emotional intelligence deficit in addicted populations.