St George's University's Medical Student Research Institute: A Novel, Virtual Programme for Medical Research Collaboration.

OBJECTIVE: Medical student research involvement has evolved to be a core component of medical education and is becoming increasingly vital to success in the United States residency match. We sought to develop a research website allowing students and research faculty to collaborate and complete projects online. METHODS: The Medical Student Research Institute (MSRI) was developed by the St George's University School of Medicine in 2009 to encourage, support, facilitate and centralize medical student research. RESULTS: There are 63 active students in the MSRI (22 students in basic science and 41 students in clinical rotations). The mean GPA for basic science student members was 3.81 ± 0.27 and was 3.80 ± 0.20 for clinical student members. The mean United States Medical Licensing Examination (USMLE) Step 1 score was 241.6 ± 17.5. Since 2009, MSRI students have published 87 manuscripts in 33 different journals and have presented at 14 different national and international conferences. CONCLUSION: A web-based MSRI provides a virtual, entirely online resource for coordinating remote research collaboration between medical students and faculty whose opportunities would be otherwise limited. Initial experiences with the programme have been positive and the framework and concept of the MSRI provides a platform for university and medical schools to provide research opportunities to students who may not have face-to-face access to research faculty.

Aortic valve replacement with and without coronary artery bypass graft surgery in octogenarians: is it safe and feasible?

INTRODUCTION: Octogenarians are often denied complex surgical intervention. We evaluated the rationality of this bias by comparing the outcomes of octogenarians undergoing aortic valve replacement (AVR) with or without coronary artery bypass grafting (CABG), to those of younger patients. METHODS: Data on 476 patients (≥ 80 years) who underwent AVR or AVR/CABG were compared to the Society of Thoracic Surgeons (STS) database. RESULTS: One hundred and seventeen octogenarians underwent AVR and 263 underwent AVR/CABG. Preoperative comorbidity rates were similar between these 2 respective groups, except for diabetes mellitus (18.8 vs. 30.4%, p = 0.02), previous cardiac stent placement (5.1 vs. 17.9%, p = 0.0006) and prior CABG (8.5 vs. 0.8%, p = 0.0002) and mortality did not differ significantly (5.1 vs. 7.6%, p = 0.51). Multivariate analysis identified preoperative chronic renal failure [odds ratio (OR) = 0.09, p < 0.048], postoperative arrhythmia (OR = 0.29, p < 0.022), sepsis (OR =37.38, p < 0.000), pneumonia (OR = 8.29, p < 0.038) and renal failure (OR = 10.16, p < 0.000) with increased rates of in hospital mortality in AVR alone and AVR/CABG. CONCLUSION: AVR alone or AVR/CABG can be safely performed in patients ≥ 80 years with acceptable morbidity/mortality rates. An age of ≥ 80 years is not an independent risk factor predictive of increased in hospital mortality

Deep Learning-Generated Synthetic MR Imaging STIR Spine Images Are Superior in Image Quality and Diagnostically Equivalent to Conventional STIR: A Multicenter, Multireader Trial.

BACKGROUND AND PURPOSE: Deep learning image reconstruction allows faster MR imaging acquisitions while matching or exceeding the standard of care and can create synthetic images from existing data sets. This multicenter, multireader spine study evaluated the performance of synthetically created STIR compared with acquired STIR. MATERIALS AND METHODS: From a multicenter, multiscanner data base of 328 clinical cases, a nonreader neuroradiologist randomly selected 110 spine MR imaging studies in 93 patients (sagittal T1, T2, and STIR) and classified them into 5 categories of disease and healthy. A DICOM-based deep learning application generated a synthetically created STIR series from the sagittal T1 and T2 images. Five radiologists (3 neuroradiologists, 1 musculoskeletal radiologist, and 1 general radiologist) rated the STIR quality and classified disease pathology (study 1, n = 80). They then assessed the presence or absence of findings typically evaluated with STIR in patients with trauma (study 2, n = 30). The readers evaluated studies with either acquired STIR or synthetically created STIR in a blinded and randomized fashion with a 1-month washout period. The interchangeability of acquired STIR and synthetically created STIR was assessed using a noninferiority threshold of 10%. RESULTS: For classification, there was a decrease in interreader agreement expected by randomly introducing synthetically created STIR of 3.23%. For trauma, there was an overall increase in interreader agreement by +1.9%. The lower bound of confidence for both exceeded the noninferiority threshold, indicating interchangeability of synthetically created STIR with acquired STIR. Both the Wilcoxon signed-rank and t tests showed higher image-quality scores for synthetically created STIR over acquired STIR (P < .0001). CONCLUSIONS: Synthetically created STIR spine MR images were diagnostically interchangeable with acquired STIR, while providing significantly higher image quality, suggesting routine clinical practice potential.

Regional differences in MRI detection of amyloid plaques in AD transgenic mouse brain.

Our laboratory and others have reported the ability to detect individual Alzheimer's disease (AD) amyloid plaques in transgenic mouse brain in vivo by magnetic resonance imaging (MRI). Since amyloid plaques contain iron, most MRI studies attempting to detect plaques in AD transgenic mouse brain have employed techniques that exploit the paramagnetic effect of iron and have had mixed results. In the present study, using five-way anatomic spatial coregistration of MR images with three different histological techniques, properties of amyloid plaques in AD transgenic mouse brain were revealed that may explain their variable visibility in gradient- and spin-echo MR images. The results demonstrate differences in the visibility of plaques in the cortex and hippocampus, compared to plaques in the thalamus, by the different MRI sequences. All plaques were equally detectable by T(2)SE, while only thalamic plaques were reliably detectable by T(2)*GE pulse sequences. Histology revealed that cortical/hippocampal plaques have low levels of iron while thalamic plaques have very high levels. However, the paramagnetic effect of iron does not appear to be the sole factor leading to the rapid decay of transverse magnetization (short T(2)) in cortical/hippocampal plaques. Accordingly, MRI methods that rely less on iron magnetic susceptibility effect may be more successful for eventual human AD plaque MR imaging, particularly since human AD plaques more closely resemble the cortical and hippocampal plaques of AD transgenic mice than thalamic plaques.

Near lethal endometriosis and a massive (64 kg) endometrioma: case report and review of the literature.

A 51-year-old morbidly obese, hypertensive, anemic, and amenorrheic female presented with anuria and respiratory symptoms. The patient had a distinctly massive abdomen with necrotic anterior abdominal wall, and laboratory findings revealed a leukocytosis, profound anemia, coagulopathy and renal failure. An abdominal sonogram showed a large, complex intra-abdominopelvic mass and ascites. At surgery, a massive, cystic left ovarian mass, 37 1 of ascitic/cyst fluid, and several peritoneal nodules were removed--a total of 64 kg of tumorous tissue. Histopathological evaluation of the mass revealed an endometrioma. We present this rare case of severe endometriosis in a morbidly obese patient who presented with an exceptionally large endometrioma (64 kg), multifactorial respiratory and renal failure, coagulopathy, and profound anemia.

Case-control study of the D2 dopamine receptor gene and smoking status in lung cancer patients.

BACKGROUND: Interindividual differences in the structure and expression of the dopamine receptor genes affect dopamine availability and may be the genetic basis for variation in vulnerability to tobacco smoking. In this study, prevalences of polymorphisms in the TaqIA allele (A1 and A2) and the TaqIB allele (B1 and B2) of the D2 dopamine receptor gene in 157 lung cancer case patients and 126 control subjects were determined to assess whether individuals homozygous or heterozygous for the less common A1 and B1 alleles are more vulnerable to nicotine addiction. METHODS: Case and control subjects were accrued from an ongoing epidemiologic study. Blood samples were collected from them and subjected to molecular genetic analyses. Subjects were interviewed to obtain relevant information. Current and former smokers were administered a questionnaire to quantify their addiction to nicotine. RESULTS: The combined B1B2 genotypes appeared to be more prevalent in ever smokers than in never smokers among case patients (30.3% versus 13.3%; two-sided P = .233) and among control subjects (30.9% and 0%; two-sided P = .02); statistically significant differences were not observed among those with A1 genotypes. Statistically significant correlations between the presence of the A1 and B1 alleles were observed (r = .73 for case subjects and r = .76 for control subjects; two-sided P<.001). Individuals with rarer genotypes reported having been substantially younger at the time of smoking initiation (statistically significant for both A1 and B1) and having attempted to quit smoking fewer times (statistically significant for only A1). CONCLUSION: Variant alleles of the D2 dopamine receptor gene may play a role in determining nicotine addiction, although the associations between the at-risk genotypes and measures of nicotine addiction were not entirely consistent.

Enhancing efficacy of recombinant anticancer vaccines with prime/boost regimens that use two different vectors.

BACKGROUND: The identification of tumor-associated antigens and the cloning of DNA sequences encoding them have enabled the development of anticancer vaccines. Such vaccines target tumors by stimulating an immune response against the antigens. One method of vaccination involves the delivery of antigen-encoding DNA sequences, and a number of recombinant vectors have been used for this purpose. To optimize the efficacy of recombinant vaccines, we compared primary and booster treatment regimens that used a single vector (i.e., homologous boosting) with regimens that used two different vectors (i.e., heterologous boosting). METHODS: Pulmonary tumors (experimental metastases) were induced in BALB/c mice inoculated with CT26.CL25 murine colon carcinoma cells, which express recombinant bacterial beta-galactosidase (the model antigen). Protocols for subsequent vaccination used three vectors that encoded beta-galactosidase--vaccinia (cowpox) virus, fowlpox virus, naked bacterial plasmid DNA. Mouse survival was evaluated in conjunction with antibody and cytotoxic T-lymphocyte responses to beta-galactosidase. RESULTS: Heterologous boosting resulted in significantly longer mouse survival than homologous boosting (all P<.0001, two-sided). Potent antigen-specific cytotoxic T lymphocytes were generated following heterologous boosting with poxvirus vectors. This response was not observed with any of the homologous boosting regimens. Mice primed with recombinant poxvirus vectors generated highly specific antibodies against viral proteins. CONCLUSIONS: The poor efficacy of homologous boosting regimens with viral vectors was probably a consequence of the induction of a strong antiviral antibody response. Heterologous boosting augmented antitumor immunity by generating a strong antigen-specific cytotoxic T-lymphocyte response. These data suggest that heterologous boosting strategies may be useful in increasing the efficacy of recombinant DNA anticancer vaccines that have now entered clinical trials.

Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines.

Activation of T lymphocytes in the absence of a costimulatory signal can result in anergy or apoptotic cell death. Two molecules capable of providing a costimulatory signal, B7-1 (CD80) and B7-2 (CD86), have been shown to augment the immunogenicity of whole-tumor cell vaccines. To explore a potential role for costimulation in the design of recombinant anticancer vaccines, we used lacZ-transduced CT26 as an experimental tumor and beta-galactosidase (beta-gal) as the model tumor antigen. Attempts to augment the function of a recombinant vaccinia virus (rVV) expressing beta-gal by admixture with rVV expressing murine B7-1 were unsuccessful. However, a double recombinant vaccinia virus engineered to express both B7-1 and the model antigen beta-gal was capable of significantly reducing the number of pulmonary metastases when administered to mice bearing tumors established for 3 or 6 days. Most important, the double recombinant vaccinia virus prolonged the survival of tumor-bearing mice. These effects were antigen specific. The related costimulatory molecule B7-2 was found to have a similar, although less impressive enhancing effect on the function of a rVV expressing beta-gal. Thus, the addition of B7-1 and, to a lesser extent, B7-2 to a rVV encoding a model antigen significantly enhanced the therapeutic antitumor effects of these poxvirus-based, therapeutic anticancer vaccines.

Comparative anatomy of the porcine and human thoracic spines with reference to thoracoscopic surgical techniques.

BACKGROUND: This study compared porcine and human thoracic spine anatomies for a better understanding of how structures encountered during thoracoscopy differ between training with a porcine model and actual surgery in humans. METHODS: Parameters were measured including vertebral body height, width, and depth; disc height; rib spacing; spinal canal depth and width; and pedicle height and width. RESULTS: Although most porcine vertebral structures were smaller, porcine pedicle height was significantly greater than that of humans because the porcine pedicle houses a unique transverse foramen. The longus colli and psoas attach, respectively, to T5 and T13 in swine and to T3 and T12 in humans. In swine, the azygos vein generally was absent. The intercostal veins drained into the hemiazygos vein. CONCLUSIONS: Several thoracoscopically relevant anatomic differences between human and porcine spinal anatomies were identified. A thoracoscopic approach in a porcine model probably is best performed from the right side. The best general working area is between T6 and T10.

A novel biochemical model linking dysfunctions in brain melatonin, proopiomelanocortin peptides, and serotonin in autism.

A novel biochemical model for autism is presented, which proposes that a subgroup of autistic individuals may have a hypersecretion of pineal melatonin that produces a cascade of biochemical effects including a corresponding hyposecretion of pituitary proopiomelanocortin (POMC) peptides and a hypersecretion of hypothalamic opioid peptides and serotonin (5-HT). The model is reviewed, and supporting animal and clinical research, is summarized. The first arm of the model suggests that increases in pineal melatonin results in hypersecretion of 5-HT in hypothalamus and blood. The second arm of the model indicates that hypersecretion of melatonin also inhibits the release of hypothalamic corticotrophin-releasing hormone (CRH). Hyposecretion of CRH may result in decreased release of both pituitary B-endorphin (B-E) and adrenocorticotrophin hormone (ACTH); this, in turn, may result in decreased plasma concentrations of B-E, ACTH, and cortisol. In autism, a genetically determined hypersecretion of hypothalamic B-E may further contribute to an inhibition of pituitary B-E because of negative feedback inhibition. Therefore, autism may reflect a dysfunction in the pineal-hypothalamic-pituitary-adrenal axis which, modulates POMC and 5-HT systems of the brain. This model is consistent with numerous clinical investigations implicating hypersecretion of brain 5-HT and opioid peptides in autism. The model may have heuristic importance in guiding future research in the biochemistry of autism.

D2 dopamine receptor gene polymorphisms among African-Americans and Mexican-Americans: a lung cancer case-control study.

Recent research suggests that variant alleles (A1 and B1) of the DRD2 gene play a role in determining smoking status. However, no studies have evaluated these variant alleles in African-Americans and Mexican-Americans. The primary objective of this study, therefore, was to test the hypothesis that ever smokers in these ethnic groups are more likely than never smokers to have the DRD2 alleles associated with tobacco use (A1 and B1). Furthermore, because of a predicted higher prevalence of smokers in a family because of the patterns of inheritance of the genotypes associated with tobacco use, we also anticipated that individuals with these at-risk DRD2 alleles would be more likely to have a family history of smoking-related cancers. Because other inherited genetic variants may interact with smoking on cancer risk, we also hypothesized that this association might differ between cancer patients and control subjects. PCR was used to perform genotyping on peripheral WBC DNA from 140 lung cancer patients (43 Mexican-Americans and 97 African-Americans) and 222 age-, sex-, and ethnicity-matched controls (111 Mexican-Americans and 111 African-Americans). A personal family history was obtained from each participant. There were no statistically significant differences in the distribution of the DRD2 genotypes between cases and controls, although the frequency of the B1 genotype significantly differed by ethnicity (P = 0.002 for controls and P = 0.001 for cases). The DRD2 genotypes and smoking status showed a correlation among Mexican-American controls, although not among African-American controls. The cigarette pack-years in control subjects for the two ethnic groups combined were 30.8, 21.9, and 18.6 for the A1A1, A1A2, and A2A2 genotypes and 36.5, 20.8, and 18.5 for the B1B1, B1B2, and B2B2 genotypes, respectively. Similar trends were found for the number of cigarettes smoked per day among control subjects. From the standpoint of polymorphisms, however, there was a borderline significantly increased (3.6 times greater) frequency of smoking-related cancers among the first-degree relatives of case subjects with an A1 allele than among those without an A1 allele. There was also an elevated (1.8 times greater) frequency of smoking-related cancer among first-degree relatives of case subjects with a B1 allele compared with patients without a B1 allele, but this finding was not statistically significant. This phenomenon was not observed among control subjects. We noted a trend toward interaction of DRD2 A1 genotypes and case status for increased risk of smoking-related cancer among first-degree relatives. These findings suggest that the variant DRD2 genotypes are associated with a greater likelihood to smoke and a greater smoking intensity, as well as with a familial aggregation of smoking-related cancers. However, a large study is needed to confirm this finding.

Identifying and recruiting healthy control subjects from a managed care organization: a methodology for molecular epidemiological case-control studies of cancer.

Case-control studies with stringent matching criteria require large pools of healthy subjects from which to select matched controls. This paper describes a successful method of identifying a large pool of potential control subjects to participate in two molecular epidemiological case-control studies of lung cancer, each enrolling 400 case subjects and 400 control subjects. These studies are not population based, and the study base is not well-defined. Therefore, potential control subjects are being identified and recruited through 20 area clinic sites of a large multispecialty health maintenance organization. Because the research focus is driven by genetic hypotheses and we are controlling for multiple smoking-related variables, representativeness is of lesser concern. To identify potential control subjects, a one-page questionnaire is distributed to patients in the waiting room to assess contact information as well as data relevant to the case-control matching process. An average of 2,228 questionnaires are returned monthly toward a target pool of 40,000; of these, 59% of the respondents fulfill eligibility criteria as a control subject for one of the studies and are not averse to being contacted in the future for the purpose of research. When compared to former smokers and never smokers, current smokers in the control population were least likely to refuse further contact. A collaborative arrangement with a managed care organization offers a feasible mechanism through which researchers can access a large, ethnically diverse population of potential control subjects.

The impact of smoking status, disease stage, and index tumor site on second primary tumor incidence and tumor recurrence in the head and neck retinoid chemoprevention trial.

Second primary tumors (SPTs) develop at an annual rate of 3-7% in patients with head and neck squamous cell cancer (HNSCC). In a previous Phase III study, we observed that high doses of 13-cis-retinoic acid reduced the SPT rate in this disease. In 1991, we launched an intergroup, placebo-controlled, double-blind study to evaluate the efficacy of low-dose 13-cis-retinoic acid in the prevention of SPTs in patients with stage I or II squamous cell carcinoma of the larynx, oral cavity, or pharynx who had been previously successfully treated with surgery, radiotherapy, or both, and whose diagnoses had been established within 36 months of study entry. As of September 16, 1999, the Retinoid Head and Neck Second Primary (HNSP) Trial had completed accrual with 1384 registered patients and 1191 patients randomized and eligible. All of the patients were followed for survival, SPT development, and index cancer recurrence. Smoking status was assessed at study entry and during study. Smoking cessation was confirmed biochemically by measurement of serum cotinine levels. The annual rate of SPT development was analyzed in terms of smoking status and tumor stage. As of May 1, 2000, SPTs have developed in 172 patients. Of these, 121 (70.3%) were tobacco-related SPTs, including 113 in the aerodigestive tract (57 lung SPTs, 50 HNSCC SPTs, and 6 esophageal SPTs) and 8 bladder SPTs. The remaining 51 cases included 23 prostate adenocarcinomas, 8 gastrointestinal malignancies, 6 breast cancers, 3 melanomas, and 11 other cancers. The annual rate of SPT development observed in our study has been 5.1%. SPT development related to smoking status was marginally significant (active versus never, 5.7% versus 3.5%; P = 0.053). Significantly different smoking-related SPT development rates were observed in current, former, and never smokers (annual rate = 4.2%, 3.2%, and 1.9%, respectively, overall P = 0.034; current versus never smokers, P = 0.018). Stage II HNSCC had a higher overall annual rate of SPT development (6.4%) than did stage I disease (4.3%; P = 0.004). When evaluating the development of smoking-related SPTs, stage was also highly significant (4.8% for stage II versus 2.7% for stage I; P = 0.001). Smoking-related SPT incidence was significant for site as well (larynx versus oral cavity, P = 0.015; larynx versus pharynx, P = 0.011). Primary tumors recurred at an annual rate of 2.8% in a total of 97 patients. The rate of recurrence was higher in patients with stage II disease (4.1% versus 2.2%, P = 0.004) as well as oral cavity site when compared with larynx (P = 0.002). This is the first large-scale prospective chemoprevention study evaluating smoking status and its impact on SPT development and recurrence rate in HNSCC. The results indicate significantly higher SPT rates in active smokers versus never smokers and significantly higher smoking-related SPT rates in active smokers versus never smokers, with intermediate rates for former smokers.

Correlates of mutagen sensitivity in patients with upper aerodigestive tract cancer.

Although tobacco and alcohol use are the major determinants of upper aerodigestive tract carcinogenesis, not all smokers develop cancer. This phenomenon is due to individual variation in genetic susceptibility to carcinogens. One explanation may be differences in mutagen sensitivity (as measured by the in vitro bleomycin-induced mutagen sensitivity assay) in patients with squamous cell carcinoma of the upper aerodigestive tract. Antioxidant supplementation has also been shown to decrease DNA damage and thus may also inhibit carcinogenesis. In this study, we examined whether smoking, alcohol intake, and dietary antioxidant intake were correlated with mutagen sensitivity. The 612 patients evaluated are part of an ongoing multicenter Phase III trial of 13-cis retinoic acid for the prevention of second primary tumors. We found that patients with pharyngeal cancers were more likely than patients with oral cavity or larynx cancers to be mutagen sensitive. There were no significant differences in the distribution of mutagen sensitivity by sex or alcohol use. Never smokers were significantly more likely (61.1%) to be mutagen sensitive than current smokers (35.6%). Dietary consumption of the micronutrients alpha-carotene, beta-carotene, lutein, lycopene, and vitamin C was not correlated with mutagen sensitivity. Therefore, we suggest that mutagen sensitivity is an independent marker of cancer risk not affected by other known risk factors.

Sociodemographic analysis of patients in radiation therapy oncology group clinical trials.

PURPOSE: To assess the degree to which the sociodemographic characteristics of patients enrolled in Radiation Therapy Oncology Group (RTOG) clinical trails are representative of the general population. METHODS AND MATERIALS: Sociodemographic data were collected on 4016 patients entered in 33 open RTOG studies between July 1991 and June 1994. The data analyzed included educational attainment, age, gender, and race. For comparison, we obtained similar data from the U.S. Department of Census. We also compared our RTOG data with Surveillance Epidemiology and End Results (SEER) data for patients who received radiation therapy, to determine how RTOG patients compared with cancer patients in general, and with patients with cancers at sites typically treated with radiotherapy. RESULTS: Overall, the sociodemographic characteristics of patients entered in RTOG trials were similar to those of the Census data. We found that, in every age group of African-American men and at nearly every level of educational attainment, the proportion of RTOG trial participants mirrored the proportion in the census data. Significant differences were noted only in the youngest category of African-American men, where the RTOG accrues more in the lower educational categories and fewer with college experience. For African-American women, we found a similar pattern in every age group and at each level of educational attainment. As with men, RTOG trials accrued a considerably larger proportion of younger, less educated African-American women than the census reported. Using SEER for comparison, the RTOG enrolled proportionately more African-American men to trials all cancer sites combined, and for prostate and head and neck cancer. In head and neck trials, the RTOG enrolled nearly twice as many African-American men than would be predicted by SEER data. In lung cancer trials, RTOG underrepresented African-American men significantly; however, there was no difference for brain cancer trials. There were no racial differences in RTOG accrual and SEER incidence data for women on trials in brain, lung, and head and neck cancer. However, the RTOG trials accrued nearly twice the proportion of African-American women in cervical cancer trials and in all sites combined, compared to the SEER data. CONCLUSIONS: Comparisons with the U.S. Census and SEER show that African-Americans are proportionally well represented in cancer clinical trials conducted by the Radiation Therapy Oncology Group. The comparative analysis indicates that all educational levels in each age group of African-Americans generally mirror the U.S. Census, with one exception. The exception is a significant overrepresentation of less-educated African-Americans in the youngest age category. This exception is counter to the expectation that better-educated patients are more likely to enroll in trials. When compared with SEER data, the RTOG trials either parallel or overrepresent African-American men and women, with the only exception being in lung cancer, where men are underrepresented. These results show that, in comparison to the Census and SEER data, the RTOG has fulfilled its commitment to enroll African-American patients in its clinical trials.

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (the Health Family Tree Study and the NHLBI Family Heart Study).

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRS > or =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRS > or =0.5 accounted for 86% of early strokes (<75 years) and 68% of all strokes. Analyses of >5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p <0.001 for CHD; r = 0.66, p <0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.

Prospects for the therapeutic use of anticancer vaccines.

Although a century has passed since initial attempts were made to stimulate the immune system to destroy tumour, the immunotherapy of cancer is still in the early stages. Historically, a variety of specific and nonspecific immunostimulatory strategies have been administered with only modest clinical success. However, recent advances in tumour immunology, most notably the identification of genes encoding for cancer regression antigens, have paved the way for the development of a variety of novel and specific vaccine approaches. These include vaccines based on tumour cells, carbohydrates, peptides and heat-shock proteins, DNA-based vaccination, and the use of recombinant bacteria and viruses to deliver antigens or the DNA coding for them. While several of these approaches have yielded exciting clinical results, a number of immunological and host obstacles to the successful application of cancer vaccines remain. Further research is needed on the optimum choice of antigen, delivery vector, adjuvant and administration regimen.

The epidemiology of chlamydial infections in childhood: a serological investigation.

Blood samples from 382 children between the ages of one and 15 years were tested for anti-chlamydial antibody. A low prevalence of antibody against Chlamydia trachomatis was found among children under the age of seven years. Antibody against the Chlamydial agent C IOL-207 was rare before the age of five years, but was found with increasing prevalence in older children. It is suggested that the mode of transmission of the two agents is different and that C IOL-207 may be transmitted at school.