Natural history of patients with abdominal aortic aneurysm

Factors determining the outcome for patients with abdominal aortic aneurysm (AAA) were analysed in a retrospective population-based study of 187 consecutively diagnosed AAAs at one hospital during a 9-year period. All aneurysms were diagnosed by ultrasound, and those cases that were not primarily operated upon, were followed by repeat ultrasound examinations. An expansion rate of more than 0.4 cm/year was seen in 27% of the aneurysms and a tendency towards a higher rate of expansion could be seen with larger lesions. The overall cumulative rupture rate was 12% at 5 years. For patients with small (less than 5 cm) aneurysms it was 2.5% at 7 years, and no aneurysm could definitively be shown to be smaller than 5 cm at the time of rupture. The rupture risk was significantly higher (28% at 3 years) for larger aneurysms (greater than or equal to 5 cm). The only reliable predictor for rupture was aneurysm size. The overall cumulative survival was 51% at 5 years. Patients with large aneurysms did not have a significantly shorter survival although a tendency for this to be the case was found. There was a significant difference between the proportion of deaths caused by aneurysm rupture in patients with small aneurysms when compared to those with large aneurysms, 5.5 and 53%, respectively. The expansion rate for AAA was highly individual and aneurysm diameter was the only recognisable predictor of rupture. The rupture rate for AAAs smaller than 5 cm was lower than previously reported.     

AN ANALYSIS OF THE SEQUENCES OF THE VARIABLE REGIONS OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS AND THEIR IMPLICATIONS FOR ANTIBODY COMPLEMENTARITY

In an attempt to account for antibody specificity and complementarity in terms of structure, human κ-, human λ-, and mouse κ-Bence Jones proteins and light chains are considered as a single population and the variable and constant regions are compared using the sequence data available. Statistical criteria are used in evaluating each position in the sequence as to whether it is essentially invariant or group-specific, subgroup-specific, species-specific, etc. Examination of the invariant residues of the variable and constant regions confirms the existence of a large number of invariant glycines, no invariant valine, lysine, and histidine, and only one invariant leucine and alanine in the variable region, as compared with the absence of invariant glycines and presence of three each of invariant alanine, leucine, and valine and two each of invariant lysine and histidine in the constant region. The unique role of glycine in the variable region is emphasized. Hydrophobicity of the invariant residues of the two regions is also evaluated. A parameter termed variability is defined and plotted against the position for the 107 residues of the variable region. Three stretches of unusually high variability are noted at residues 24–34, 50–56, and 89–97; variations in length have been found in the first and third of these. It is hypothesized that positions 24–34 and 89–97 contain the complementarity-determining residues of the light chain—those which make contact with the antigenic determinant. The heavy chain also has been reported to have a similar region of very high variability which would also participate in forming the antibody-combining site. It is postulated that the information for site complementarity is contained in some extrachromosomal DNA such as an episome and is incorporated by insertion into the DNA of the structural genes for the variable region of short linear sequences of nucleotides. The advantages and disadvantages of this hypothesis are discussed.     

Impact of the use of heptavalent pneumococcal conjugate vaccine on disease epidemiology in children and adults

Pneumococcal conjugate vaccine was introduced for routine use in infants and toddlers in the United States in March 2000. We report on the impact of the introduction of this vaccine on disease epidemiology in young children as well as secondary effects due to herd immunity in unvaccinated children and adults. As of March 2003, 157,471 children had received one or more doses of PNCV7, but only 24% of those less than two years of age received all four doses as a result of shortages of vaccine. During the last year of observation, no cases of vaccine serotype disease were seen in children less than one year of age compared with an incidence ranging between 51.5 and 98.2 cases/100,000 person years (16-34 cases per year) in the years before vaccine introduction. Similar reductions were seen in children less than five years of age. There was no evidence of any concomittant increase in pneumococcal disease caused by non-vaccine serotypes. High-level resistance of pneumococci to penicillin fell from a peak of 15% in year 2000 to 5% in the first half of 2003.