Philip W. Lam

Activation of human B lymphocytes by 8′ substituted guanosine derivatives

The 8-substituted guanosine derivatives (8-sGs), mercaptoguanosine and bromoguanosine, are shown to induce immunoglobulin production and proliferation in a subset of normal human B lymphocytes. Limiting dilution analysis indicated that the 8-sG-responsive B cell pool is approximately 10 times larger than that activated by pokeweed mitogen (PWM), 10 times smaller than that activated by Epstein-Barr virus (EBV), and contains approximately equal proportions of cells committed to the expression of IgG, IgA or IgM isotypes. Although some B cells seem able to respond to 8-sGs in the absence of T helper cells, maximal immunoglobulin production is only observed in the presence of T cells. The 8-sG response pattern of human B lymphocytes appeared similar but not identical to that reported for rodent cells. The mitogenic 8-sGs are unique activators as they bypass surface membrane interactions obligatory for other agents including anti-IgM, Staphylococcus aureus particles, PWM, and EBV.

Lymphocyte function in human bone marrow. II: Characterization of an interleukin 2-sensitive T precursor-cell population

In the present study of human bone marrow lymphocytes, we analyze a newly recognized population of T suppressor-cell precursors which are found in marrow only and which have the potential to inhibit immunoglobulin (Ig) productionin vitro. Following exposure to interleukin 2 (IL2), suppressor precursors acquire E receptor, T3 determinants, suppressor function, and lectin responsiveness. To distinguish this population within the framework of T-cell ontogeny, it was compared to a previously described population of thymus-dependent helper T-cell precursors which express helper function following exposure to thymus-derived mediators. The two populations are completely distinct and can be separated on density gradients. Suppressor precursors expressed T8 and TAC (IL2-receptor) antigens prior toin vitro induction with IL2. The thymic hormone-dependent cells expressed T4 but not T8 or TAC determinants. In two patients with severe combined immunodeficiency disease (SCID), IL2-responsive precursor cells appeared only late after thymus epithelium transplantation, perhaps best explained by a model in which thymus-dependent differentiation pathways precede, induce, or seed pathways of extrathymic T-cell differentiation. The large pool size of over 1011 suppressor and helper precursor cells present in adult bone marrow suggests that these populations may play an important role in immune homeostasis.

Regulation of human in vitro anti-hapten responses: Demonstration of a carrier effect

Abstract Human peripheral blood mononuclear cells, tonsillar lymphocytes, or mixtures of allogeneic or autologous B and T cells from these tissues were stimulated in vitro with the soluble hapten:carrier complexes TNP-OA, TNP-KLH, TNP-Myo, or TNP-Lac. These complexes were able to induce TNP-specific, direct PFC during 5–6 days in culture. The response involved proliferating PFC precursor B cells, nonproliferating T helper cells, and radiosensitive T-suppressor cell precursors. Exposure to high concentrations of free or carrier-bound hapten resulted in the inactivation of PFC precursor B cells. Carrier specific suppressor T cells could be induced by priming with nonhaptenated carrier protein and were able to block the PFC response when added to fresh target cultures. The use of hapten:carrier complexes permits the characterization of distinct T-cell functions independently of the assay system for B-cell activation.

Impact of Defaulting to Single-Lumen Peripherally Inserted Central Catheters on Patient Outcomes: An Interrupted Time Series Study

Defaulting to single-lumen peripherally inserted central catheters (PICCs) ordered from non-critical care units resulted in a sustained reduction in PICC-related complications. This system of care is transferrable to other institutions, with potential for improved patient safety and efficiency in outpatient parenteral antimicrobial therapy clinics.

Microbacterium Peritonitis in Peritoneal Dialysis: A Case Report and Review

Peritoneal dialysis-related peritonitis (PDRP) is a commonly encountered complication in patients undergoing peritoneal dialysis (PD). Establishing the causative organism in PDRP allows for targeted antibiotic selection, helps to guide duration of therapy, and determines the need for catheter removal. Microbacterium is a genus of aerobic gram-positive bacilli found in the environment. Its detection in clinical isolates has increased owing to improved microbiology diagnostics. We present a case of PDRP due to M. paraoxydans and review the epidemiology, clinical manifestations, and available evidence for treatment of this organism. The high rate of recurrent infection and limited data regarding antimicrobial susceptibility testing pose significant challenges in the management of PDRP caused by Microbacterium species.

Mandibular osteomyelitis due to Raoultella species

Introduction Raoultella is a genus of aerobic Gram-negative bacilli belonging to the family Enterobacteriaceae that are commonly found in water, soil and aquatic environments. With improved bacterial identification techniques, Raoultella species (namely R. planticola and R. ornithinolytica) have been an increasingly reported cause of infections in humans. Case presentation An 85-year-old man presented to hospital with a several-week history of left jaw pain and trismus. His medical history was significant for left mandibular osteomyelitis treated 1 year previously with amoxicillin-clavulanate. On admission, a computed tomography scan demonstrated a 2.6×1.7×1.6 cm peripherally enhancing collection surrounding the left posterior mandibular body. Two aspirates of the abscess grew a bacterium belonging to the genus Raoultella, with discordant species identification (R. ornithinolytica versus R. planticola) using two different techniques. A potential source of infection included a left lower molar tooth which was extracted months preceding the original diagnosis of osteomyelitis. Conclusion This is the first case of mandibular osteomyelitis caused by Raoultella species reported in the literature. In contrast to other forms of osteomyelitis, the pathogenesis of mandibular osteomyelitis involves contiguous spread from an odontogenic focus. Risk factors for mandibular osteomyelitis include a history of fracture, irradiation, diabetes and steroid therapy. This report adds to the growing literature of infections caused by this genus of bacteria, and raises the possibility of this organism’s role in odontogenic infections.

Nosocomial outbreak of vanD-carrying vancomycin-resistant Enterococcus faecium

Samir N. Patel PhD, Andrew E. Simor MD and Jerome A. Leis MD, MSc Department of Medicine, University of Toronto, Toronto, Ontario, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada, Public Health Ontario, Public Health Ontario Laboratory, Toronto, Ontario, Canada, Infection Prevention and Control, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada and Division of Infectious Diseases, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada

Medical management of Salmonella enteritidis prosthetic valve endocarditis with multiple infectious foci

(0.9 × 0.85 × 1.1 cm) valve, thickening of the proximal aorta suggestive of a peri-annular aortic root abscess, and a large echogenic mass on the right ventricular pacemaker lead [2]. Abdominal imaging demonstrated evidence of splenic infarcts. Due to an unacceptably high surgical risk, a trial of medical management was sought with an aim to reduce disease burden followed by chronic suppressive therapy. He completed a 6 week course of ceftriaxone followed by oral trimethoprim/sulfamethoxazole (TMP/SMX) 800 mg/160 mg twice daily as chronic suppressive therapy. His symptoms resolved and he remains clinically well after 12 months of follow-up while adherent to TMP/SMX. This represents the first reported case of S. enteriditis endocarditis involving two mechanical valves, an aortic root graft, and a pacemaker lead. Indications for surgery include an infected cardiac implantable electronic device [3], large valvular vegetations (> 10 mm), and a peri-annular abscess [4]. A review by Gönen et al. found that 10 of 13 reported cases of S. enteritidis prosthetic valve endocarditis required surgical intervention. Of the four cases involving two prosthetic valves, three underwent valve replacement, and one died pre-operatively [5]. Our case demonstrates that in selected individuals, treatment with intravenous antibiotic followed by oral chronic suppressive therapy is an option. TMP/SMX was chosen based on its excellent oral bioavailability, relatively narrow spectrum of activity, and low cost. Finally, this case highlights a potential occupational risk for developing Salmonella bacteremia. Patients with a history of immunosuppression or prosthetic implant should be counseled on the risk of salmonellosis through certain occupational exposures. To the Editor,

Sinister seafood: bacteraemia secondary to non-O1/O139 Vibrio cholerae infection

Introduction. Vibrio species are curved, motile Gram-negative bacilli found in estuarine and marine environments, and are known to cause to gastroenteritis, skin and soft tissue infections, and septicaemia. While not responsible for cholera epidemics, non-O1/O139 Vibrio cholerae (NOVC) is increasingly reported as a cause of gastroenteritis. Case presentation. A 66-year-old man presented to an emergency department with a 1 week history of epigastric pain, emesis and fever. Blood cultures drawn on admission initially demonstrated Gram-negative bacilli, and ultimately grew NOVC, which was later confirmed by matrix-assisted laser desorption ionization-time of flight MS. Subsequent history revealed that the patient had eaten fish and seafood prior to falling ill. He was treated with intravenous ceftriaxone and oral doxycycline while admitted, and oral ciprofloxacin and doxycycline upon discharge. His bacteraemia was believed to be secondary to altered gut anatomy from prior surgery and proton-pump inhibitor use. Conclusion. Risk factors for NOVC bacteraemia include cirrhosis, immunosuppression and other forms of liver disease. Cases are often linked to a history of seafood ingestion when water temperatures rise, enabling Vibrio species to proliferate. While the optimal management of NOVC bacteraemia is unclear, a combination of a third-generation cephalosporin with a tetracycline has been suggested. Physicians should maintain a high index of suspicion for this pathogen when evaluating ill patients with a history of liver disease and seafood ingestion.