Pilot study of an HLA-A2 peptide vaccine using flt3 ligand as a systemic vaccine adjuvant

A pilot vaccine study was conducted to test the safety and immunological efficacy of four monthly immunizations of an MHC class I peptide vaccine, the E75 HLA-A2 epitope from HER-2/neu, using flt3 ligand as a systemic vaccine adjuvant. Twenty HLA-A2-expressing subjects with advanced stage prostate cancer were randomly assigned to one of four immunization or treatment schedules: (a) Flt3 ligand (20 g/kg per day) administered subcutaneously daily for 14 days on a 28-day cycle, monthly for four months; (b) flt3 ligand course as above with the E75 peptide vaccine administered on day 7 of each flt3 ligand cycle; (c) flt3 ligand course as above with the E75 peptide vaccine administered on day 14 of each flt3 ligand cycle; or (d) E75 peptide admixed with granulocyte–macrophage colony-stimulating factor and administered intradermally once every 28 days, as has previously been reported. The primary endpoints of the study were the determination of safety and immunological efficacy in generating E75-specific T cells as determined by peptide-specific interferon-gamma ELIspot. Adverse events included one grade 3 skin reaction and the development of grade 2 autoimmune hypothyroidism in two subjects with preexisting subclinical autoimmune hypothyroidism. Dendritic cells were markedly increased in the peripheral blood of subjects receiving flt3 ligand with each repetitive cycle, but augmentation of antigen-presenting cells within the dermis was not observed. Apart from a single subject, no significant peptide-specific T-cell responses were detected by ELIspot, whereas delayed-type hypersensitivity responses were detectable in control subjects and in subjects receiving peptide vaccine early in the course of flt3 ligand administration. The absence of robust peripheral immune responses in the current study may be attributable to the small numbers of subjects or differences in the subject population. In addition, the inability of flt3 ligand to augment the number of peripheral skin antigen-presenting cells may have contributed to the absence of robust peptide-specific immunity detectable in the peripheral blood of immunized subjects treated with flt3 ligand.     

An Evaluation of Breastfeeding Promotion Through Peer Counseling in Mississippi WIC Clinics

Objective: This study evaluates the effectiveness of a peer counseling program at increasing breastfeeding by participants in the Mississippi Special Supplemental Nutrition Program for Women, Infants and Children (WIC). Methods: Data from the 1989–1993 Pediatric Nutrition Surveillance System were analyzed to compare breastfeeding rates in clinics with and without peer counseling programs. A questionnaire completed by program staff to describe the program in greater detail helped identify characteristics associated with greater success. Results: The incidence of breastfeeding rose from 12.3% to 19.9% in those clinics with peer counseling programs, but only from 9.2% to 10.7% in clinics without a program. Clinics that started a program earlier showed greater changes in breastfeeding incidence. However, the presence of lactation specialists or consultants in the clinic appeared to be more important than the presence of less-trained peer counselors. Peer counselors who spent more than 45 minutes per participant were more effective than those spending less time. Conclusions: The peer counseling program significantly increased the incidence of breastfeeding, particularly in clinics with lactation specialists and consultants. Success can be enhanced by ensuring that peer counselors spend a great deal of time with the participants.     

Is the Degree of Arrhythmia Suppression a Predictor of Survival?

The effectiveness of an antiarrhythmic drug is judged by the degree of ventricular arrhythmia suppressed by the drug. It has been suggested that a certain degree of ventricular arrhythmia suppression should be targeted to prove efficacy. Targets used to define the effectiveness of an antiarrhythmic agent included an 80% reduction in the ventricular premature complexes (VPCs) and 90% suppression of nonsustained ventricular tachycardia (NVT) episodes or complete abolition of runs of sustained VT (SVT) [1]. Other dose-adjusted antiarrhythmic trials have attempted to achieve either isolated control of the PVCs of greater-than-or-equal70% [2--5] with the suppression of the high grades of arrhythmia such as couplets and NVT of >90% and 100%, respectively [2, 3]. Such targets of arrhythmia suppression were recommended to avoid errors encountered with the occurrence of the spontaneous variability of ventricular arrhythmia and to be confident that antiarrhythmic therapy has produced a true drug effect [6]. Presently, there is no evidence that suppression of these arrhythmias with type I antiarrhythmic drugs is likely to reduce sudden death [4, 6]. The survival of patients with frequent VPCs and high-grade forms (couplets [C], NVT) and organic heart disease is not dependent on the degree of arrhythmia suppression. The survival of patients with low LVEF of <40% and runs of NVT is improved and is similar to that of patients with good LVEF of greater-than-or-equal40%. Such a lack of correlation between arrhythmia suppression and survival might be a unique feature of the antifibrillatory drugs and might not be applied to the antiectopic drugs. If a high degree of arrhythmia suppression is not needed, lower targets of suppression may be necessary. Lower drug dosages may improve the risk--benefit ratio of antiarrhythmic treatment.     

Laparoscopic gastrostomy versus percutaneous endoscopic gastrostomy

A retrospective study was carried out at our institution to compare patients who underwent percutaneous endoscopic gastrostomy (PEG) to those who underwent laparoscopic gastrostomy (LG). There were 17 patients who had a PEG with a mean age of 81 years (43–97 years). The procedure time, including complete esophago-gastroduodenoscopy, averaged 28 min. There were four deaths (23%) in a 30-day period, but none of these were directly related to the procedure. The LG group consisted of 14 patients with a mean age of 66 years (20–94 years). Mean duration of the procedure was 18 minutes. Thirty-day mortality rate was 35% (five patients) with one death (7%) directly related to the tube. Indications for gastrostomy were similar in both groups, being predominantly inability to eat and/or recurrent aspiration. However, LG was done because of 4 technical failures, 5 patients with tumors of the head and neck, 2 patients with esophageal obstruction and radiation stenosis precluding safe PEG, and 1 patient with hiatal hernia; 2 LGs were performed at the surgeon’s preference. Outcomes for LG and PEG were comparable. LG is a suitable, safe alternative to PEG in selected patients who cannot undergo gastroscopy and should be considered the procedure of choice in patients with head and neck tumors or intrathoracic pathology that prevents PEG.     

Rating the appropriateness of coronary angiography, coronary angioplasty and coronary artery bypass grafting: the ACRE study. Appropriateness of Coronary Revascularisation study

BACKGROUND: Previous studies investigating the appropriateness of invasive management of coronary disease had not reported the internal consistency of their ratings and may now be out of date. The aim of this study was to measure the influence of clinical factors on contemporary ratings of the appropriateness of coronary angiography, percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft (CABG) in the Appropriateness of Coronary Revascularisation (ACRE) study. METHODS: The Delphi-RAND technique was used, in which an expert panel (four cardiologists, three cardiothoracic surgeons, a general physician and a general practitioner), meeting in 1995, rated mutually exclusive indications (n = 2178 for angiography, n = 995 for PTCA and n = 984 for CABG). The main outcome measures were the appropriateness category (inappropriate, uncertain or appropriate) for each of the three procedures and treatment preference. RESULTS: For revascularization, the strongest determinant of inappropriateness was coronary anatomy. The odds ratio (OR) for inappropriate PTCA was 10.6 (95 per cent confidence interval (CI) 4.8-23.5) for the effect of left main stem or three-vessel disease versus single-vessel disease, and for CABG it was 0.06 (95 per cent CI 0.03-0.15). The number of diseased vessels was strongly related to preference for medical, PTCA or CABG treatment (p for linear trend <0.001). Mild versus severe anginal symptoms were associated with inappropriate angiography (OR 2.0 (95 per cent CI 0.9-9.8), although this effect was stronger when only the cardiologists' ratings were considered (OR 10.1 (95 per cent CI 2.4-42.6)). CONCLUSION: These are the first UK ratings of appropriateness covering all three procedures. The associations with clinical factors provide evidence of the internal consistency of these ratings. Prospective validation of these ratings against clinical outcomes is under way in the ACRE study.     

Is the Degree of Arrhythmia Suppression a Predictor of Survival?

The effectiveness of an antiarrhythmic drug is judged by the degree of ventricular arrhythmia (VA) suppression. We evaluated the relationship between the degree of VA suppression and survival in a dose-adjusted trial of 110 symptomatic patients treated with amiodarone. Cohorts had left-ventricular ejection fraction (LVEF) of 41 plus minus 18%, ventricular premature contractions (VPCs) of 445 plus minus 571 h, couplets (C) of 733 plus minus 1498 24 h and nonsustained (N) ventricular tachycardia (VT) of 65 plus minus 217 24 h; these conditions were followed for 15 plus minus 11.5 months. Amiodarone was initiated with an oral loading of 670 plus minus 111.7 mg per day for 10 days and continued on maintenance of 274.9 plus minus 102 mg per day. Survival rates of responders and nonresponders with VPCs <70%, 70--89%, greater-than-or-equal90%; C greater-than-or-equal 90%; NVT (100%); and the response to all 3 criteria (suppresion of VPCs greater-than-or-equal70%, C greater-than-or-equal 90% and complete abolition of NVT) were not statistically significant. Survival rates as a function of LVEF <40% (51 patients) or greater-than-or-equal40% (59 patients), as well as responders or nonresponders to all three criteria, were not significant (p = NS). We conclude that, in patients treated with low-dose amiodarone, the degree of VA suppression of PVCs, C and NVT does not predict survival; the survival of patients with LVEF <40% improved irrespective of VA suppression; and criteria for VA suppression should be reassessed at lower levels of suppression for the improvement of the drug risk:benefit ratio. More improvement is not necessarily better.     

Magnetic Resonance Angiography of the Abdominal Aorta

Magnetic resonance angiography (MRA) of the abdominal aorta was performed in 36 patients using the "bright-blood" technique on the basis of a series of flow-compensated breath-hold 2 D-GE pulse sequences. Diverse diseases included complete occlusion, stenosis, atherosclerotic or dissecting aneurysm and renal artery stenosis. Coronal and axial projection angiograms [maximum intensity projection (MIP) algorithm] and individual GE images were compared with DSA and contrast-enhanced computed tomography (CT). Our data showed a good correlation of MR and digital subtraction arteriography (DSA) or CT resp. in all cases, when both rotating MIP angiograms and individual GE images were analyzed. Thus, MR is suggested to be a useful noninvasive diagnostic method for the abdominal aorta, particularly in preoperative staging of aneurysms, aortic occlusive disease, and stenosis of the proximal main renal artery. Drawbacks of the method are a signal loss in slow or turbulent flow conditions, and unsatisfactory spatial resolution in small vessels.