Immunogenetic studies in families with rheumatoid arthritis and autoimmune thyroid disease.

HLA and Gm typing were carried out in 16 families. Seven families included 10 sib pairs with rheumatoid arthritis (RA) and autoimmune thyroid disease (ATD) respectively, and nine families included 16 sib pairs with RA and circulating thyroid autoantibodies respectively. Eight, 11, and seven sib pairs with either RA or clinical or immunological evidence of ATD shared none, one, and two HLA haplotypes respectively, and two, seven, and two informative sib pairs shared none, one, and two Gm haplotypes respectively. This random haplotype sharing of HLA and Gm haplotypes suggests that non-HLA, non-Gm linked genes are likely to be involved in any genetic predisposition common to RA and ATD.     

Role of cell-mediated immunity in the resolution of secondary chlamydial genital infection in guinea pigs infected with the agent of guinea pig inclusion conjunctivitis.

Guinea pigs which have recovered from a genital infection with the agent of guinea pig inclusion conjunctivitis demonstrate strong immunity to reinfection for a short period of time but then become susceptible to reinfection. The secondary infection is markedly shortened in duration and decreased in intensity. Previous studies have indicated an important role for humoral immunity in resistance to and in recovery from reinfection. However, the contribution of cell-mediated immunity to immunity toward or recovery from a secondary infection is not clear. Guinea pigs were infected in the genital tract with guinea pig inclusion conjunctivitis and were challenged at either 30 or 75 days after the primary infection. Prior to challenge, one group of animals were injected with rabbit anti-guinea pig thymocyte serum (ATS) while control groups received either normal rabbit serum or no treatment. Treatment was continued daily for the course of the experiment. On day 30, ATS-treated guinea pigs had a slightly higher rate of reinfection, and generally the infection persisted longer than in controls. On day 75, all animals became reinfected upon challenge, but control animals resolved their infections in 3 to 9 days. In contrast, most ATS-treated animals remained infected throughout the course of the experiment. Although the animals became reinfected, the levels of chlamydiae were much lower than those observed during the primary infection. ATS treatment abrogated T-cell responses, but serum and secretory antibody responses remained normal. Histopathological examination revealed some decrease in mononuclear infiltration of endocervical and uterine tissues in ATS-treated animals. These data indicate that previously infected guinea pigs require both cell-mediated immunity and humoral immunity for resolution of a challenge infection.     

Fibrous encapsulation of single polymer microfibers depends on their vertical dimension in subcutaneous tissue

The purpose of this research was to investigate possible explanations for why small-diameter microfiber implants do not experience encapsulation in subcutaneous tissue as do large-diameter fiber implants. Single polypropylene microfibers of approximately rectangular cross-section with rounded edges were twisted about their longitudinal axes and affixed at their ends to polycarbonate frames. The frames were implanted in rat subcutaneous dorsum for a 5-week period, then removed and processed for light microscopy analysis. Fibrous capsule presence/absence and thickness around the implants were assessed, and their relationships to geometric features of the fibers investigated. A logistic regression analysis between presence/absence of a fibrous capsule and geometric features of interest demonstrated strong predictive ability (92.4% correct predictions) for implant height and a well-defined threshold separating the presence and absence of a fibrous capsule at 5.9 microm (p < 0.001). Implant height was defined as the vertical distance between the most superficial and deepest level of the implant. This 5.9-microm threshold value of implant height is comparable to the 6.0-microm diameter threshold for capsule presence/absence in fibers of circular cross-section [Sanders et al. J Biomed Mater Res 2000; 52(1):231-237]. Fiber major axis length, minor axis length, aspect ratio, surface area per unit length, implant width, and implant angle did not show similar predictive ability or a well-defined threshold separating the presence and absence of a fibrous capsule. It is reasoned that for fibers greater than the threshold height of 5.9 microm, separation of collagen fibers in the extracellular matrix creates dead space regions adjacent to the fibers that attract inflammatory cells and stimulate fibrous capsule formation.     

Journal Club. HIV-associated bacterial pneumonia

Bacterial pneumonia is the most common cause of death from pneumonia in patients with HIV disease, causing greater mortality than Pneumocystis carinii pneumonia. The challenge for the clinician evaluating the HIV-infected patient with pneumonia is to quickly distinguish clinically among all possible causes and to initiate therapy based on the most likely diagnosis. While an understanding of typical clinical and radiographic presentations is essential, bronchoscopy is the preferred test for reliably identifying the causative organism.     

Small fiber diameter fibro-porous meshes: tissue response sensitivity to fiber spacing

The purpose of this research was to determine if fiber spacing for small fiber diameter fibro-porous meshes affected tissue response in vivo. Disk-shaped polyurethane meshes, with mean fiber diameters of 7.6 microm and fiber spacing between 6 and 68 microm, were implanted in rat subcutaneous dorsum for 5-week intervals and then prepared for light microscopy and morphological analysis. Results showed that implants with 12- to 68-microm spacing had no histologically apparent fibrous capsule around the perimeter, a result different from that for 6-microm spacing samples that had a capsule around a mean of 34.2% of the perimeter. For the 12- to 68-microm spacing range, a mean of 21.0% of individual fibers within the meshes were encapsulated. Qualitatively, it appeared that larger fibers were encapsulated more frequently than smaller ones. When nodeless or baggy meshes were implanted, cells tended to cluster three or more fibers into groups and then encapsulate each group. Over the 6- to 68-microm spacing range, cell nuclei volume fraction within the meshes increased from the 6- to the 29-microm spacing (p = 0.000) and then decreased from the 29- to the 68-microm spacing (p = 0.015). There was a trend of an increase in local vessel volume fraction with spacing over the 6- to 68-microm range, though the relationship was weak. The results indicate that the reason for the lack of encapsulation of small-fiber fibro-porous meshes is not exclusively a pore boundary explanation, as is proposed for small-pore porous meshes.     

A simple and reliable method to screen isolates of Escherichia coli and Klebsiella pneumoniae for the production of TEM- and SHV-derived extended-spectrum β-lactamases

Objective: To evaluate which of 24 β-lactams used in susceptibility tests best discriminated between strains of Klebsiella pneumoniae and Escherichia coli that produce extended spectrum β-lactamases (ESBLs) from strains that produce older, more familiar, plasmid-mediated β-lactamases such as TEM-1 and SHV-1.
Methods: Susceptibility to the 24 β-lactam agents was determined by agar dilution and disk diffusion methodologies, using 27 strains of K. pneumoniae and E. coli that produced 22 different older plasmid-mediated β-lactamases and 28 strains that produced 17 different ESBLs.
Results: In general, strains that produced ESBLs were intermediate or resistant to cefpodoxime, whereas those that produced other β-lactamases were susceptible to this agent. The agar dilution test exhibited 96% sensitivity and 100% specificity in discriminating these two groups of organisms. The disk diffusion test exhibited 100% sensitivity and 96% specificity. All other β-lactam agents tested were inferior discriminators between the two groups of organisms.
Conclusions: Agar dilution and disk diffusion tests with cefpodoxime can be used to discriminate strains of K. pneumoniae and E. coli that produce ESBLs from those that produce older, plasmid-mediated β-lactamases.     

Detection of extended-spectrum-beta-lactamase-producing members of the family Enterobacteriaceae with Vitek ESBL test.

A three-phase analysis of the Vitek ESBL test and a double-disk (2 disk) test was performed to assess their ability to detect extended-spectrum beta-lactamases (ESBLs) in members of the family Enterobacteriaceae. In the first two phases involving detection of ESBLs in 157 stains processing well-characterized beta-lactamases, sensitivity and specificity were found to be 99.5 and 100%, respectively, for the Vitek ESBl test and 98.1 and 99.4%, respectively, for the 2-disk test. In the third phase, in which the ability of each test to detect ESBLs in 295 clinical isolates was assessed, there was only one false positive (Vitek ESBL test). Across all three phases, the Vitek ESBL test was found to be much easier to perform than the 2-disk test. The latter also involved subjective interpretation of results. There were a total of 176 Escherichia coli and 157 Klebsiella pneumoniae isolates and less than 40 isolates of each of 14 other species evaluated. In a supplemental study of Klebsiella oxytoca, an organism possessing a chromosomal beta-lactamase similar to an ESBL, the Vitek ESBL test was found to be capable of detecting hyperproduction of this enzyme in strains of this species as well. These data indicate that the Vitek ESBL test is reliable for the detection of ESBLs in E. coli and K. pneumoniae, the two species in which ESBLs are most common, and of hyperproduction of the K. oxytoca beta-lactamase, a situation which engenders a level of resistance to this species similar to that seen with ESBLs.