B lymphocyte differentiation in the rat: production and characterization of monoclonal antibodies to B lineage-associated antigens

Three mouse monoclonal antibodies (mAb) directed against rat B lineage antigens were produced. The mAb, designated HIS14 (IgG1), HIS22 (IgM) and HIS24 (IgG2b), were characterized for binding to lymphoid and nonlymphoid tissues by immunoperoxidase staining of frozen sections and by (double-) immunofluorescence staining of single cell suspensions from lymphoid organs. HIS14 recognized a pan B cell determinant: it reacted with virtually all cells of each anatomic B cell compartment and with about 95% of surface (s)Ig+ cells in thoracic duct lymph and in suspensions of spleen and lymph nodes. HIS22 and HIS24 detected B lineage-associated antigens expressed by major subpopulations of B cells. HIS22 predominantly stained the lymphocyte corona, but not (or weakly) the germinal centers and splenic marginal zones, whereas HIS24 reacted with both corona and germinal center and not (or weakly) with marginal zone. In accordance with this, substantial proportions of sIg+ cells in spleen cell suspensions did not express HIS22 or HIS24 determinants (20% and 27%, respectively). In bone marrow the vast majority of cytomplasmic mu+ pre-B cells were HIS14+ and HIS24+, and up to one third also HIS22+, indicating an appearance of the determinants early in B lymphocytopoiesis. The antigens recognized by HIS14, HIS22 and HIS24 are lost during the final stage of B cell differentiation: none of the mAb bound to plasma cells. As far as detectable, neither cells of myeloid and erythroid lineages in bone marrow nor thymocytes were stained by HIS14, HIS22, or HIS24. In suspensions of peripheral lymphoid organs (spleen and lymph nodes) but not in thoracic duct lymph, HIS14 and HIS24 labeled a small proportion (12% and 14%, respectively) of Ig- cells. HIS22 did not bind to Ig- peripheral lymphocytes. Reactivity of HIS14, HIS22 and HIS24 with nonlymphoid tissues was virtually absent; HIS22 stained the high endothelial venules in lymph nodes and Peyer's patches. As determined by immunoblotting, the antigenic determinants on lymph node cells recognized by HIS14, HIS22 and HIS24 were present on molecules with an apparent molecular mass of 205 kDa, 210 (and 175) kDa and 205 kDa, respectively, which is similar to the molecular mass of the B cell form of the rat leukocyte common antigen. In addition, the antigens recognized by HIS14, HIS22 and HIS24 co-capped with the leukocyte common antigen. This suggests that each of the three mAb recognize determinants present on the B cell form of the leukocyte common antigen.     

Introducing a pneumococcal vaccine to an existing influenza immunization program: vaccination rates and predictors of noncompliance.

PURPOSE: Influenza vaccination has been recommended for all elderly people in The Netherlands since 1996, with greater than 80% compliance. It is unknown, however, if the addition of another vaccine to this immunization program will affect compliance. SUBJECTS AND METHODS: General practitioners offered a pneumococcal vaccine together with the yearly influenza vaccination to 3365 patients aged 65 years and older. A questionnaire was then mailed to a stratified sample (n = 972) of these patients. Factors associated with noncompliance with vaccination were assessed using polytomous logistic regression. RESULTS: A total of 2529 patients (75%) received the pneumococcal vaccine and 2812 (84%) received the influenza vaccine. Predictors of noncompliance with the pneumococcal vaccine were perceived lack of recommendation by the general practitioner (odds ratio [OR] = 4.6; 95% confidence interval [CI], 2.6 to 8.3) and fear of local side effects (OR = 2.8; 95% CI, 1.6 to 4.6). Predictors of noncompliance with both vaccinations also included unwillingness to comply with the doctor's advice (OR = 6.1; 95% CI, 2.4 to 15.4), the belief that vaccinations weaken one's natural defenses (OR = 2.7; 95% CI, 1.4 to 5.3) or that influenza is not dangerous (OR = 2.9; 95% CI, 1.5 to 5.4), and the fear of becoming sick from pneumococcal vaccination (OR = 2.9; 95% CI, 1.1 to 7.9). People who felt healthy, found it difficult to visit the doctor's office, had private medical insurance, or were younger than 75 years of age also had a greater risk of not being vaccinated. CONCLUSION: Introducing a pneumococcal vaccine to an existing influenza immunization program resulted in high pneumococcal and influenza vaccination rates. A wider diversity of patient characteristics and attitudes was present when neither vaccination was received.     

LAMA tumor in the rat as an experimental model for pre-B-cell leukemia

A late pre-B-cell leukemia model in the rat, the LAMA tumor, is described. A mouse monoclonal antibody (HIS30) was developed against LAMA cells. HIS30 reacts with a membrane antigen in tumor tissue, whereas its reactivity with normal tissues is limited to the zona glomerulosa of the adrenal cortex and to the adrenal medulla. HIS30 was used for both the immunohistological detection of tumor cells in tissue sections and the immunolocalization of tumor cells in vivo. To enable in vitro studies with the LAMA model, an in vitro growing cell line (LAMA-K1) was established from the LAMA tumor. LAMA-K1 is immunophenotypically similar to the original tumor. Two tumor transplantation models were characterized. In the first model LAMA was implanted s.c., and local tumor growth occurred at the injection site, which was then followed by lymphatogenic and subsequently hematogenic tumor spread. In the second model i.v. transplantation caused direct hematogenic tumor dissemination. In both models early dissemination was especially prominent to the bone marrow, spleen, and liver. Later in the disease most visceral organs became involved, and partial paralysis of the animal was observed in the end stage of the disease. In combination with HIS30, the LAMA pre-B-cell tumor offers a model for both the investigation of in vivo transplanted tumor cells and for the in vivo detection of tumor cells by HIS30 in LAMA tumor-bearing rats.     

Assessing the potential effects and cost-effectiveness of programmatic herpes zoster vaccination of elderly in the Netherlands

Background  

Herpes zoster (HZ) is a painful disease affecting a considerable part of the elderly. Programmatic HZ vaccination of elderly people may considerably reduce HZ morbidity and its related costs, but the extent of these effects is unknown. In this article, the potential effects and cost-effectiveness of programmatic HZ vaccination of elderly in the Netherlands have been assessed according to a framework that was developed to support evidence-based decision making regarding inclusion of new vaccines in the Dutch National Immunization Program.     

Predicting postherpetic neuralgia in elderly primary care patients with herpes zoster: prospective prognostic study

Postherpetic neuralgia (PHN) is the most frequent complication of herpes zoster (HZ) and difficult to treat. Timely identification of high-risk HZ-patients enables physicians to focus on PHN prevention. To assess which simple to measure factors are independent predictors of PHN, and whether psychosocial and serological/virological parameters have additional predictive value, a prospective cohort study in primary care was conducted. We included 598 elderly (>50 years) consecutive patients with acute HZ (rash <7 days) below sixth cervical dermatome. At baseline demographic, clinical (e.g., duration and severity of pain and rash), psychological (Pain Cognition List [PCL] and Spielberger's Anxiety Inventory), serological (VZV-antibodies) and virological (viremia presence) variables were measured. Blood tests were performed in a random subset of 218 patients. Primary outcome was significant pain (VAS >30 on 0-100 scale) after three months. The final prediction model obtained from multivariable logistic regression was (internally) validated using bootstrapping techniques, and adjusted for optimism. Forty-six (7.7%) patients developed PHN. Independent predictors were age (odds ratio [OR]=1.08 per year), acute pain severity (OR=1.02 per unit), presence of severe rash (OR=2.31), and rash duration before consultation (OR=0.78 per day): area under receiver-operating-characteristic curve [ROC area]=0.77 (95% CI: 0.71-0.82). Of the five PCL scores, only factor V ('trust in healthcare') was an additional predictor (OR=1.01 per unit), though it increased the ROC area with only 0.01 to 0.78. The Spielberger's anxiety scores and serological and virological variables were no additional predictors. Thus, four simple variables can help physicians to timely identify elderly HZ-patients at risk of PHN.     

Treatment of herpes zoster

OBJECTIVE

To review the evidence regarding treatment of herpes zoster (HZ) in the short-term, focusing on the prevention of postherpetic neuralgia (PHN).

QUALITY OF EVIDENCE

The evidence relating to treatment of HZ is derived mainly from randomized controlled trials (level I evidence).

MAIN MESSAGE

Antiviral drugs might have some effect on the severity of acute pain and on the duration of skin lesions. Corticosteroids also alleviate acute pain. Oral antiviral medication reduces the risk of eye complications in patients with ophthalmic HZ. There is no convincing evidence that antiviral medication reduces the risk of PHN. Some studies, however, have shown that famciclovir and valacyclovir shorten the duration of PHN. The effectiveness of amitriptyline or cutaneous and percutaneous interventions in preventing PHN has not been proven.

CONCLUSION

Oral antiviral drugs should be prescribed to elderly HZ patients with high risk of PHN. Moreover, these drugs should be prescribed to all patients at the first signs of ophthalmic HZ, irrespective of age or severity of symptoms.     

Summary of the Dutch College of General Practitioners (NHG) practice guideline on 'Diverticulitis'

The NHG practice guideline on 'Diverticulitis' provides general practitioners with directions on the diagnosis and treatment of uncomplicated and complicated diverticulitis. Diverticulitis is primarily a clinical diagnosis which can be supported by assessment of CRP. Uncomplicated diverticulitis is strongly suspected if the patient reports the development of persistent sharp, stabbing pain in the lower left abdomen within a couple of days; if there is pressure or rebound tenderness only in the lower left abdomen; and if there are no alarm signals. Alarm signals of complicated diverticulitis are: guarded muscle response, signs of intestinal obstruction, locally palpable resistance, rectal loss of blood, hypotension, and high fever. The policy for uncomplicated diverticulitis is waiting without specific measures, provided that the general practitioner monitors the course actively. There is no indication for antibiotics in patients with uncomplicated diverticulitis. Patients with signs of complicated diverticulitis or with persisting symptoms should be referred.