Therapeutic vaccines: realities of today and hopes for the future

Vaccines are by definition prophylactic, but in recent years an interest has developed in therapeutic vaccines for infectious diseases such as AIDS and tuberculosis, as well as gastric ulcers, cancer (with different approaches to combat various types of malignancy) and autoimmune diseases (a definite success was the development of a vaccine against multiple sclerosis) and there are potential vaccines in development for myasthenia gravis, lupus and diabetes. Therapeutic vaccines are also being developed against cognitive diseases such as Alzheimer's disease, prion diseases and Huntington's disease. All of these efforts are based on the therapeutic vaccine being closely related chemically to the etiological agent that causes the disease.     

Dichloroacetate treatment for severe refractory metabolic acidosis during neonatal sepsis

We describe a preterm neonate with documented group B Streptococcus sepsis and associated metabolic acidosis whose lactic acidemia was refractory to conventional sodium bicarbonate therapy but responded well to dichloroacetate treatment.     

Measurements of bone turnover markers in premature infants

We determined the levels of circulating bone turnover markers in preterm infants during the first weeks of life. Twenty premature infants (mean gestational age 27+/-2.2 weeks, mean birth weight 894+/-231 g) hospitalized in the neonatal intensive care unit (NICU) at the Meir General Hospital, Israel, participated in the study. Measurements of bone turnover markers were performed at birth, and every week thereafter for an average follow-up of 11.2+/-0.7 weeks. Bone osteoblastic activity was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP) and the C-terminal procollagen peptide (PICP) levels. Bone resorption was assessed by measurements of serum levels of the carboxy-terminal cross-links telopeptide of type I collagen (ICTP). All three markers of osteoblastic activity increased markedly and significantly during the first three weeks of life, and then continued to increase gradually until week 10 (p<0.01). Circulating ICTP levels increased in the first week of life and then decreased gradually throughout the follow-up (p<0.01). The study participants were divided into premature infants born at extremely low birth weight (ELBW: <1000 g, n=12) and very low birth weight (VLBW: 1000-1250 g, n=8). Osteocalcin (in weeks 2-5 of life), PICP (weeks 3-5), and ICTP levels (weeks 2-3) were significantly higher in VLBW preterms. These results suggest increased bone formation in premature infants in the first three months of life. The increased bone turnover in VLBW compared to ELBW premature infants may be the result of a generally higher morbidity in ELBW preterm infants in early stages of life.     

Risk factors for incomplete excision of basal cell carcinomas

Incomplete excision of basal cell carcinomas (BCCs) may be followed by recurrence of the tumor. In order to detect risk factors for incomplete excision of BCCs we performed a cross-sectional study of 1278 patients who underwent a primary excision of BCCs, during a four-year period, within an ambulatory and hospital plastic surgery department setting. Incomplete excision occurred in 159 of 1478 primary excisions of BCCs (10.8%) and was significantly associated with location of the tumors in the eyelids (OR 3.64, 95% CI 1.96-6.71), ears (OR 2.51, 95% CI 1.25-4.94), naso-labial folds (OR 2.26, 95% CI 0.99-5.04) and nose (OR 1.88, 95% CI 1.30-2.71). There was an inverse association with location of the tumors in the upper limbs (OR 0.44, 95% CI 0.21-0.90), back (OR 0.12, 95% CI 0.02-0.48) or chest (OR 0.09, 95% CI 0.00-0.57). Baso-squamous differentiation was associated with incomplete excision of BCCs (p = 0.03). No association was observed between incomplete excision of BCCs and gender, age, setting of the operation (ambulatory vs. hospital), clinical appearance of the lesion (suspected BCCs vs. other diagnoses) or diameter of the lesions. In conclusion, incomplete excision of BCCs was associated with location of the tumors in the eyelids, ears, naso-labial folds and nose. We recommend that in patients with BCCs located in these sites, surgeons should commence particular surgical measures to avoid inadequate excisions of the tumors.     

Molecular aspects of oral cancer

Squamous cell carcinoma of the oral cavity is the sixth most frequent cancer in the world with approximately 30,000 new cases diagnosed annually in the United States. The overall 5-year survival rate for patients with oral squamous cell carcinoma is among the lowest for major cancers and has not changed during the past two decades. Despite therapeutic and diagnostic progress in oncology during the past decades, the prognosis of intraoral squamous cell carcinoma remains poor. Thus it seems that finding a biological tumor marker or tumor markers which will increase the early diagnosis and treatment monitoring rates, is of paramount importance in respect to improving prognosis. The latest studies pertaining to tumor markers and their role in the detection, diagnosis and treatment monitoring of oral squamous cell carcinoma are reviewed. The importance of cell surface markers including blood antigens, and growth factors and receptors, and intercellular markers including cytokeratins and AgNORs are discussed. Particular attention is paid to quantitative DNA (aneuploidy) and oncogenes. The pivotal tumor suppressor gene, p53, is dealt with in depth.     

Preterm labour at 34–36 weeks of gestation: should it be arrested?

Currently, preterm labour is treated with tocolytic agents and prenatal steroids until the 34th week of gestation only. Our objective in this study was to assess this practice. Seven-year records of all preterm infants born in our institution at 34--36 weeks of gestation, were evaluated retrospectively. All babies, born in singleton well-dated pregnancies, without maternal, medical or obstetric complications, and by normal vaginal delivery, were included. Their length of hospital stay and perinatal complications were compared across gestational age groups of 34, 35 and 36 weeks. Of the 207 babies included, statistically significant reductions in the rates of respiratory distress syndrome (15.0% vs. 3.2%), nosocomial sepsis (5.0% vs. 0%) and apnoea of prematurity (11.7% vs. 2.2%), and consequently, in length of hospital stay (16 +/- 2.7 vs. 4 +/- 0.3 days) occurred between 34 and 36 weeks of gestation. The severity of respiratory distress syndrome also declined significantly. The changes were most noticeable after 35 weeks of gestation, and it was concluded that neonatal complications are still prevalent at 34 and 35 weeks. Therefore, we propose that labour should not be induced at 34 and 35 weeks of gestation and that tocolytic agents and maternal prenatal steroids may be considered in preterm labour during this period.     

Botulinum toxin as a biological weapon: medical and public health management

OBJECTIVE: The Working Group on Civilian Biodefense has developed consensus-based recommendations for measures to be taken by medical and public health professionals if botulinum toxin is used as a biological weapon against a civilian population. PARTICIPANTS: The working group included 23 representatives from academic, government, and private institutions with expertise in public health, emergency management, and clinical medicine. EVIDENCE: The primary authors (S.S.A. and R.S.) searched OLDMEDLINE and MEDLINE (1960-March 1999) and their professional collections for literature concerning use of botulinum toxin as a bioweapon. The literature was reviewed, and opinions were sought from the working group and other experts on diagnosis and management of botulism. Additional MEDLINE searches were conducted through April 2000 during the review and revisions of the consensus statement. CONSENSUS PROCESS: The first draft of the working group's consensus statement was a synthesis of information obtained in the formal evidence-gathering process. The working group convened to review the first draft in May 1999. Working group members reviewed subsequent drafts and suggested additional revisions. The final statement incorporates all relevant evidence obtained in the literature search in conjunction with final consensus recommendations supported by all working group members. CONCLUSIONS: An aerosolized or foodborne botulinum toxin weapon would cause acute symmetric, descending flaccid paralysis with prominent bulbar palsies such as diplopia, dysarthria, dysphonia, and dysphagia that would typically present 12 to 72 hours after exposure. Effective response to a deliberate release of botulinum toxin will depend on timely clinical diagnosis, case reporting, and epidemiological investigation. Persons potentially exposed to botulinum toxin should be closely observed, and those with signs of botulism require prompt treatment with antitoxin and supportive care that may include assisted ventilation for weeks or months. Treatment with antitoxin should not be delayed for microbiological testing.     

The Sexual Abuse of Male Children and Adolescents: A Review of Current Research

Inevitably, in a wide ranging review, there will be some important omissions. The main difficulties in assessing the available information have been the lack, in so many studies, of analysis along gender lines, the lack of control groups, and, in many instances, too small sample size. Despite these limitations there has, over the past decade, been an upsurge of interest in and awareness of the significance of the sexual abuse of boys. It permits us to identify a number of important trends and to draw certain conclusions. Firstly, the scale of the sexual abuse of boys is much greater than was believed 10 years ago. There is no reason to think this is simply an artifact of definition, or information gathering, or indeed of an increased willingness to recognize abusive behaviour between children, even though these will all have an effect. Whilst the trend is clear, the actual prevalence rate is difficult to determine, with a reported range of between 3% and 31%. A current 'best guess' suggests contact abuse in the range of 2-5% in the male population. As each study controls for its own definition of abuse, the narrowing in the ratio of boys to girls abused can be accepted as quite reliable, and additional evidence of a delayed recognition effect. Retrospective community evidence shows 1 boy is abused for every 2-4 girls abused. In contrast, the highest clinical ratios are for 1 boy to every 4 girls. Those who work with runaways, male child prostitutes, or child and adolescent psychiatric inpatient units appear particularly likely to encounter abused boys. Secondly, a variety of explanations have been advanced to explain the apparent under-reporting or under-detection of the sexual abuse of boys. Prominent among them have been the boy's fears of disbelief and of being labelled homosexual. Police patterns of reporting extra-familial abuse may mask its extent from protection or health agencies, which is important because extra-familial abuse does appear to be more common in boys, especially older boys, than girls. Although there has been some diminution of the cultural denial that girls can be abused, a parallel decrease of denial regarding boys has lagged behind. This is particularly true of father-son and of the much less common mother-son abuse. It is plausible that certain 'alertors' are more relevant for boys. The recent development of aggressive behaviour, homophobic anxiety, co-abuse of a sibling and abusing behaviour in particular deserve consideration.(ABSTRACT TRUNCATED AT 400 WORDS)