Effect of Prior Experimental Human Enteropathogenic Escherichia coli Infection on Illness following Homologous and Heterologous Rechallenge

Two studies of adult volunteers were performed to determine whether prior enteropathogenic Escherichia coli (EPEC) infection confers protective immunity against rechallenge. In the first study, a naive control group and volunteers who had previously ingested an O55:H6 strain were fed an O127:H6 strain. In the second study, a control group and volunteers who had previously ingested either the O127:H6 strain or an isogenic eae deletion mutant of that strain were challenged with the homologous wild-type strain. There was no significant effect of prior infection on the incidence of diarrhea in either study. However, in the homologous-rechallenge study, disease was significantly milder in the group previously challenged with the wild-type strain. Disease severity was inversely correlated with the level of prechallenge serum immunoglobulin G against the O127 lipopolysaccharide. These studies indicate that prior EPEC infection can reduce disease severity upon homologous challenge. Further studies may require the development of new model systems.

Enteropathogenic Escherichia coli (EPEC) strains are one of several categories of pathogenic E. coli strains that cause diarrhea. EPEC infections are prevalent on six continents (5, 22–24, 28, 43). In many parts of the world, EPEC strains are the most common bacterial cause of diarrhea in infants (7, 21, 43). Disease due to EPEC can be severe, refractory to oral rehydration, protracted, and lethal (3, 14, 21, 45, 48).The pathogenesis of EPEC infection involves three distinct stages, initial adherence, signal transduction, and intimate attachment (12). Initial adherence is associated with the production of a type IV fimbria, the bundle-forming pilus (BFP) (20), that is encoded on the large EPEC adherence factor (EAF) plasmid (50). EPEC uses a type III secretion apparatus to export several proteins, including EspA, EspB, and EspD, that are required for tyrosine kinase-mediated signal transduction within the host cell (17, 25, 30, 31). This signaling leads to phosphorylation and activation of a 90-kDa protein that is a putative receptor for the bacterial outer membrane protein intimin (44). Intimin, the product of the eae gene, is required for intimate attachment of bacteria to the host cell membrane and for full virulence in volunteers (13, 26, 27). The interaction between EPEC and host cells results in the loss of microvilli and the formation of adhesion pedestals containing numerous cytoskeletal proteins (16, 33, 34, 39, 46). This interaction between bacteria and host cells is known as the attaching and effacing effect (40).One of the most striking clinical features of EPEC infections is the remarkable propensity of these strains to cause disease in very young infants. Rare reports of disease in older children and adults usually reflect common-source outbreaks that probably involve large inocula (47, 53). In contrast, in nosocomial outbreaks among neonates, EPEC spreads rapidly by person-to-person contact, apparently involving low inocula (54). The incidence of community-acquired EPEC infection is highest in the first 6 months after birth (4, 7, 21). EPEC infection is also more severe in younger children (8). Infants are more likely to develop diarrhea during the first episode of colonization with EPEC than they are during subsequent encounters (8). Whether the low incidence of EPEC diarrhea in older children and adults is due to acquired immunity or decreased inherent susceptibility is not known.The immune response to EPEC infection remains poorly characterized. It has previously been demonstrated that volunteers convalescing from experimental EPEC infection develop antibodies to the O antigen component of lipopolysaccharide (LPS) of the infecting strain, to intimin, and to type I-like fimbriae (13, 15, 29, 38). Antibodies to common EPEC O antigens are found more often in children of greater than 1 year in age than they are in younger children (42). Breast-feeding is protective against EPEC infection (2, 19, 43, 52). Breast milk contains antibodies against EPEC O antigens and outer membrane proteins and inhibits EPEC adherence to tissue culture cells (6, 9, 49).In an earlier study, it was reported that volunteers infected with EPEC developed antibodies to a 94-kDa outer membrane protein (38). Subsequently, it was determined that this antigen was intimin (26). Interestingly, the lone volunteer in that earlier study who did not have diarrhea after challenge with a wild-type EPEC strain had prechallenge serum antibodies to intimin. This led to the hypothesis that antibodies to intimin are protective against EPEC infection. To test this hypothesis and to test the more general hypothesis that EPEC infection induces protective immunity, two volunteer studies were performed. The first was a heterologous-challenge study performed in 1986, in which volunteers were infected with an O55:H6 EPEC strain and challenged, along with a naive cohort, with an O127:H6 EPEC strain. The second was a homologous-challenge study performed in 1991, in which veterans of a study comparing the virulence of a wild-type EPEC O127:H6 strain with that of an isogenic eae mutant (13) were rechallenged, along with a naive cohort, with the homologous wild-type strain. The availability of new purified antigens allowed us to analyze data from these studies in the context of humoral immune responses.     

The financing of NMR equipment

Cost-containment regulations and possible legislative changes in the tax area are creating new environments for the acquisition of nuclear magnetic resonance (NMR) systems. Shared services, management groups, and free-standing clinics are being established. Creativity in financing will be required to assure the cost-effectiveness of NMR services.     

Hypnotizability and dissociation

The author describes the multidimensionality of hypnosis itself and hence of hypnotizability. He also points to the lack of clarity regarding the concept of dissociation and the extent to which its roots lie in the clinical experience of hypnosis. The concept of dissociation increasingly preempts repression and other defense mechanisms in current nosological thinking. The author cautions against equating hypnotizability scores with dissociative capacity and advocates a clearer elaboration of the concept of dissociation. Meanwhile, restraint in the use of the term "dissociation" is recommended.     

Clinical and genetic features of variegate porphyria in a Chinese patient

Acute porphyria is rare in orientals. We describe a Chinese woman with recurrent generalised tonic-clonic seizures and abdominal pain. Genomic DNA studies identified a heterozygous base substitution from guanine to adenine at nucleotide position 503, resulting in substitution of arginine by histidine at position 168 of the protein (R168H). This genetic abnormality is similar to the mutation reported in Caucasians with variegate porphyria. To the best of our knowledge, this is the first report in the English literature a Chinese patient with variegate porphyria with an identifiable mutation. A brief review of porphyria is presented.     

Der(16)T(1-16) is a nonrandom secondary chromosome aberration in many types of human neoplasia, including myxoid liposarcoma, rhabdomyosarcoma and Philadelphia-chromosome-positive acute lymphoblastic-leukemia

An unbalanced translocation between chromosomes 1 and 16, der(16)t(1;16), resulting in trisomy 1q and loss of genetic material from 16q, has been thus far suggested to constitute a nonrandom secondary abnormality in two types of closely related solid tumors - Ewing sarcoma and peripheral primitive neuroepithelial tumor (PNET). We report on three cases of soft tissue tumors, a myxoid liposarcoma, a PNET and a rhabdomyosarcoma, and four cases of hematologic disorders, two acute lymphoblastic leukemias (ALL), an acute mixed leukemia and a refractory anemia, that in addition to primary chromosome abnormalities displayed the presence of the der(16)t(1;16). All three cases of acute leukemia were Philadelphia (Ph) chromosome-positive and all displayed both lymphoid and myeloid antigens. Our results and review of the literature indicate that the occurrence of der(16)t(1;16) is not limited to Ewing sarcoma and PNET, but that acquisition of this abnormality may represent a more general pathway of clonal evolution in several different tumor types including Ph chromosome-positive ALL, myxoid liposarcoma, rhabdomyosarcoma, breast cancer, endometrial adenocarcinoma, myelodysplastic syndromes, acute myeloid leukemia, retinoblastoma, and Wilms' tumor.     

The hospital admissions study in England: are there alternatives to emergency hospital admission?

STUDY OBJECTIVE--To assess the potential for substituting alternative forms of care for admission to an acute hospital in particular groups of patients. DESIGN--A screening tool, the intensity-severity-discharge review system with adult criteria (ISD-A), developed for hospital utilisation review in the USA, was used in a cohort of hospital admissions to identify a group of patients who could potentially have been treated outside the acute hospital. These patients were further assessed by a panel of general practitioners (GPs) to determine the most appropriate alternative form of care. A cost analysis was performed on the results obtained. SETTING--General medicine and geriatric specialties in one acute hospital in the south western region. PATIENTS--Patients comprised a sample of 701 admitted to general medical and geriatric specialties. MAIN RESULTS--The screening tool identified 19.7% of admissions for whom there was potential for treatment outside the acute hospital. Assessment by the GP panel reduced this potential to between 9.8% and 15.0% of emergency admissions. The alternatives most frequently identified as "most appropriate" were the community hospital/GP bed and the urgent outpatient assessment (within either 24 or 48 hours). Potential resource savings based on the average cost were relatively small. This potential seemed to be greater for the alternative of the urgent outpatient assessment. CONCLUSIONS--Potential exists for treating a proportion of patients in lower intensity alternatives to the acute hospital. If this potential were exploited few resource savings would occur.     

Botox for rejuvenation of the periorbital region

Botulinum toxin (Botox) has become accepted as a unique and effective agent for treating various aesthetic concerns. The periorbital anatomy is particularly well suited for Botox treatments and is the most frequent site to benefit from the cosmetic application of the toxin. Therapy is aimed at paralyzing specific muscles in order to reverse their effects on the overlying skin. Cosmetic benefits of Botox treatment include smoother, line-free skin, improved brow contour, and optimal post surgical healing in certain circumstances. Botox therapy is simple, effective, and forgiving, making it very popular among physicians and patients alike. This chapter provides a review of botulinum toxin and practical information regarding its use for aesthetic application in the periorbital region.     

Respiratory and ventilatory management of critically ill children during transport

As more and more pediatric intensive care units are established throughout the country, transport systems for critically ill children assume increasing importance. This article concerns the personnel, equipment, and other requirements for a transport system and reviews the respiratory and ventilatory management of pediatric patients during transport.