Immunogenicity and Safety of Two Different Haemophilus influenzae Type b Conjugate Vaccines in Korean Infants

The incidence of invasive diseases, including meningitis caused by Haemophilus influenzae type b (Hib) was markedly decreased after routine immunization of Hib vaccine through diverse schedules in many countries. The purpose of this study was to evaluate the immunogenicity and safety of Hib conjugate vaccines in Korean children before the implementation of a national immunization program against Hib in Korea. A multicenter controlled trial was performed on two different Hib vaccines in Korean children. A total of 319 infants were enrolled: 199 infants were immunized with the Hib polysaccharide conjugated to the tetanus toxoid (PRP-T) and 120 infants with the Hib polysaccharide conjugated to the outer-membrane protein of Neisseria meningitides (PRP-OMP). Immunogenicity was evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay. Both vaccines showed good immunologic responses after primary immunization. After 2 doses of PRP-T or PRP-OMP, 78.9% and 91.7% of infants achieved an antibody level of ≥1.0 µg/mL, respectively. Both vaccines were safe and well-tolerated. No serious adverse events were observed. Thus, Hib conjugate vaccines appear to be safe and show good immunogenicity in Korean infants. These results will be important reference data for the implementation of Hib vaccine in the national immunization program of Korea.     

Differential activation of mouse hepatitis virus-specific CD4+ cytotoxic T cells is defined by peptide length.

In this study we have characterized the core epitope recognized by the MHV-A59-specific CD4+ cytotoxic T lymphocyte (CTL) clones HS1 and B6.1, derived from BALB/c and C57/BL6 mice, respectively. These CD4+ clones respond to the promiscuous peptide fragment S-329-343 of the glycoprotein S of MHV-A59. The results indicate that the core peptides of both clones overlap but are not identical. The core region of the HS1 clone is an 8-mer, and comprises the amino acid residues S-332-339, whereas the minimal epitope for clone B6.1 is a 9-mer and comprises the amino acid residues S-334-342. The peptide fragment S-329-343 activates all T-cell effector functions, including proliferation, cytokine secretion and cytolysis. However, in the present study we show that T-cell activation is not an all-or-none phenomenon, in which T-cell stimulation leads to activation of all T-cell effector functions. It appears that changes in the length of a peptide ligand can differentially activate the cytolytic machinery from proliferation and cytokine secretion. Furthermore, the results indicate that, in our case, modulation of the flanking residues of the core epitopes did not convert the cytokine profile of polarized T-helper type-1 (Th1) clones into a Th2-type pattern.     

A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

BK polyomavirus interstitial nephritis in a renal allograft recipient

Human polyomavirus (PV) interstitial nephritis has recently been recognized as a cause of severe renal allograft dysfunction. It occurs in immunosuppressed patients after reactivation of the latent virus PV type BK (BK virus) in the renal epithelium. BK disease is defined as a morphologically manifest renal infection with cytopathic signs accompanied by varying degrees of interstitial inflammatory cell infiltrates and functional impairment. It is also identified by the presence of cells containing viral inclusion bodies (decoy cells) in the urine. The authors report a case of BK PV interstitial nephritis in a 36-year-old renal allograft recipient. Under light microscopy the chief diagnostic indicator was detection of intranuclear viral inclusions, which were found exclusively in tubular epithelial cells. Cells with viral changes were often enlarged with nuclear atypia and chromatin basophilia. Widespread interstitial plasma cell infiltrates associated with tubulitis were present. Intranuclear paracrystalline arrays of virus particles 35-38 nm in diameter were present as characteristic ultrastructural indicators. Urine samples revealed decoy cells with ground-glass-type intranuclear inclusions positive for BK virus by electron microcopy.     

Nocardia osteomyelitis in a pachymeningitis patient: an example of a difficult case to treat with antimicrobial agents

Antimicrobial agents played a miraculous role in the treatment of bacterial infections until resistant bacteria became widespread. Besides antimicrobial-resistant bacteria, many factors can influence the cure of infection. Nocardia infection may be a good example which is difficult to cure with antimicrobial agents alone. A 66-year-old man developed soft tissue infection of the right buttock and thigh. He was given prednisolone and azathioprine for pachymeningitis 3 months prior to admission. Despite surgical and antimicrobial treatment (sulfamethoxazole-trimethoprim), the infection spread to the femur and osteomyelitis developed. The case showed that treatment of bacterial infection is not always as successful as was once thought because recent isolates of bacteria are more often resistant to various antimicrobial agents, intracellular parasites are difficult to eliminate even with the active drug in vitro, and infections in some sites such as bone are refractory to treatment especially when the patient is in a compromised state. In conclusion, for the treatment of infections, clinicians need to rely on laboratory tests more than before and have to consider the influence of various host factors.     

Emergence and wide dissemination of CTX-M-type ESBLs, and CMY-2- and DHA-1-type AmpC beta-lactamases in Korean respiratory isolates of Klebsiella pneumoniae

Respiratory isolates of Klebsiella pneumoniae in Korea during 2002-2003 were studied to determine the prevalence and types of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated AmpC beta-lactamases (PABLs). ESBL-production was tested by double-disk synergy, and genotypes of beta-lactamases were determined by PCR and sequencing. ESBLs were detected in 28.4% of 373 isolates, and the most prevalent types were SHV-12 (63 isolates) and CTX-M-14 (9 isolates). Forty of 75 ESBL-producers (53.5%) also had PABLs: 21 isolates with CMY-2-like, 17 with DHA-1-like. Pulsed-field gel electrophoresis showed 19 types and 25 of 74 isolates had an identical pattern, indicating nosocomial spread. Dissemination of ESBL- and PABL-producing K. pneumoniae strains in Korea is a particular concern, as it limits the choice of antimicrobial agents for treatment of infections.     

Sonographic findings of breast hamartoma: emphasis on compressibility

The characteristic features of hamartoma in terms of discrepancies in mammographic and sonographic shapes of the mass were evaluated. We reviewed 16 pathologically proven breast hamartomas, which had undergone preoperative mammography and ultrasonography. All masses were analyzed according to ACR-BIRADS on mammography. On sonography, each mass was analyzed for size, shape, margin, internal echogenicity, and posterior acoustic enhancement. We also analyzed the echogenicity of halo, and compared the characteristic changes in the shape of hamartomas attributable to compression in mammograms and sonograms. The most common sites were at 12 o'clock in the right breast and 2 o'clock in the left. The most common mammographic findings of the hamartomas were a round shape (11/16), a circumscribed margin (13/16), internal fat densities (D4)(16/16) and radiolucent halos (14/16). The most common sonographic findings of the hamartomas were an oval shape (16/16), circumscribed margins (10/16), heterogeneous internal echogenicity (14/16), echogenic (7/16) or echolucent halos (5/16), and posterior enhancements (12/16). The characteristic feature of hamartomas was a change of the mammographic round shape mass into an elongated oval shape mass by sonography (11/11), suggesting the compressibility of hamartomas. Three of the hamartomas contained a pathologically proven internal calcification. The presence of a hamartoma was suggested by a change in a mammographic round mass with a radiolucent halo into an oval heterogeneous mass surrounded by an echogenic or echolucent halo on the sonogram. This characteristic difference between the mammographic and sonographic findings was attributed to the hamartoma compressibility, and was associated with the over-proliferation of fat containing mature normal breast tissue.