Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) vs. a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine in meningococcal vaccine-naïve and meningococcal C conjugate vaccine-primed toddlers: a phase III randomised study.

Vaccination remains the best strategy to reduce invasive meningococcal disease. This study evaluated an investigational tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MenACYW-TT) vs. a licensed tetanus toxoid-conjugate quadrivalent meningococcal vaccine (MCV4-TT) (NCT02955797). Healthy toddlers aged 12-23 months were included if they were either meningococcal vaccine-naïve or MenC conjugate (MCC) vaccine-primed (≥1 dose of MCC prior to 12 months of age). Vaccine-naïve participants were randomised 1:1 to either MenACYW-TT (n = 306) or MCV4-TT (n = 306). MCC-primed participants were randomised 2:1 to MenACYW-TT (n = 203) or MCV4-TT (n = 103). Antibody titres against each of the four meningococcal serogroups were measured by serum bactericidal antibody assay using the human complement. The co-primary objectives of this study were to demonstrate the non-inferiority of MenACYW-TT to MCV4-TT in terms of seroprotection (titres ≥1:8) at Day 30 in both vaccine-naïve and all participants (vaccine-naïve and MCC-primed groups pooled). The immune response for all four serogroups to MenACYW-TT was non-inferior to MCV4-TT in vaccine-naïve participants (seroprotection: range 83.6-99.3% and 81.4-91.6%, respectively) and all participants (seroprotection: range 83.6-99.3% and 81.4-98.0%, respectively). The safety profiles of both vaccines were comparable. MenACYW-TT was well-tolerated and demonstrated non-inferior immunogenicity when administered to MCC vaccine-primed and vaccine-naïve toddlers.

Multicentric Castleman disease and systemic lupus erythematosus phenotype in a boy with Klinefelter syndrome: long-term disease stabilization with interferon therapy.

An 11-year-old boy with Klinefelter syndrome had Castleman disease (CD) of plasma cell type develop. Nonregulated antibody production mimicked systemic lupus erythematosus (SLE). Hepatitis C virus (HCV) infection caused significant disease worsening. The patient was treated with a daily dosage of 2 million units/m2 of IFN-alpha. Dramatic clinical improvement and decreasing autoimmune phenomenon were observed. HCV RNA were cleared. Hypergammaglobulinemia did not change. The boy has been living for 8 years with his disease. Plasma cell type CD can mimic collagenosis. Disease worsening is caused by HCV, though it can be reversed with IFN-alpha. Klinefelter syndrome may be a genetic susceptibility factor for CD in some cases.

Treatment patterns for heart failure in a primary care environment.

Little published information regarding current pharmacotherapeutic treatment patterns for congestive heart failure (CHF) in nonacademic, ambulatory care settings is available. We sought to assess, in a nonacademic primary care environment, pharmacotherapeutic treatment patterns for CHF with respect to consistency with clinical trial evidence and published treatment guideline recommendations. Over an 18-month period, we examined CHF pharmacotherapy using a computerized, integrated clinical diagnoses and prescription database from an outpatient community healthcare center without academic affiliations. We identified adult patients meeting contact criteria and with diagnosis of CHF by International Classification of Diseases (ICD-9-CM) coding and assessed prescribed therapy as well as select comorbid conditions. Drugs of interest included those with known or suspected benefit or detriment and those with unproven benefit. An eligible group of 14,983 patients was identified, from which a cohort of 148 patients with CHF was selected. Forty-one percent of these 148 patients were prescribed an angiotensin converting enzyme (ACE) inhibitor, 34% digoxin, 12% diuretic, 12% hydralazine + nitrate, 20% inhaled beta-agonists, and 66% warfarin. Only 5% of patients were prescribed the combination of an ACE inhibitor, digoxin, and diuretic. Thirty-one percent had a comorbid diagnosis of atrial fibrillation, of whom 44% were prescribed digoxin, 22% diltiazem, 15% beta-blockers, 15% digoxin and diltiazem, 7% digoxin and a beta-blocker, and 33% warfarin. In general, recommended therapies for CHF appeared underutilized in this cohort, whereas those of unclear benefit and potential detriment appeared overutilized. Although these results may not be readily generalized to the entire healthcare system, they do suggest a need for additional analysis and potential intervention.

Patient preferences for thrombolytic therapy in acute myocardial infarction.

BACKGROUND: Despite extensive professional debate regarding the optimal thrombolytic therapy strategy in acute myocardial infarction (AMI), patient preferences have not been explored. METHODS: Preferences among patients with known or suspected coronary artery disease for treatment with tissue plasminogen activator (tPA) or streptokinase (SK) for AMI were determined using a questionnaire presenting GUSTO-1 trial and drug cost data. Preferences were based on consideration of 30-day mortality (M) alone, hemorrhagic stroke rate (SR) alone, overall preference (M + SR), drug acquisition costs, and the estimated annual costs of using a single agent to treat all AMIs. Cost-related responses were provided under payer designations of self, third-party insurance, and federal government. RESULTS: The response rate was 81% (101/125 patients). tPA was preferred by 84%, and SK by 66%, for M alone and SR alone, respectively (chi 2, p < 0.01). Overall preference (M + SR) favored tPA (78%, p < 0.01). tPA preference decreased to 43% considering drug acquisition costs under the self-pay option (p < 0.01 vs M + SR). Similar trends of lesser magnitude were also observed for the third-party and government-payer options. CONCLUSIONS: Under conditions of zero cost and consideration of mortality plus stroke-risk data, tPA were preferred overall due to its lower mortality. Introduction of drug-cost data significantly shifted the preference toward SK, particularly under the self-payer designation. Patient preferences for thrombolytic therapy in AMI indicate tradeoffs between clinical attributes and costs, and should assist in framing medical debate and decision making.

Prolonged quinidine half-life with associated toxicity in a patient with hepatic failure.

A markedly prolonged quinidine elimination half-life due to hepatic failure and resultant quinidine toxicity occurred in a 57-year-old man with a history of atrial fibrillation. A prolonged QT interval, development of torsades de pointes, and a serum quinidine concentration of 3.1 micrograms/ml contributed to a decision favoring permanent pacemaker implantation. The apparent quinidine half-life ranged from 66-99 hours and was associated with QT prolongation and persistent U waves. On discontinuing quinidine, all signs associated with toxicity resolved as serum quinidine concentrations decreased, which resulted in reversal of the decision to implant a permanent pacemaker. This case reports an extremely long quinidine elimination half-life and reillustrates the importance of drug pharmacokinetics in patient care.

Interferon-alpha in childhood haematological malignancies.

The application of cytostatics has brought about a breakthrough in the treatment of childhood haematological malignancies in the past 20 years. Chemotherapy appears to be least successful in the rare, low and very high mitotic index diseases, which often have an enormous tumour-burden. The suitability of chemotherapy in minimal residual leukaemia is also of some doubt. In these situations a 'conservative' treatment may be more appropriate. Because interferon-alpha has a distinct mechanism of action, and a broad-spectrum haematopoietic inhibitory activity, it is relatively nontoxic and noncancerogenic, and it may have a role in the treatment of malignant haematological disorders, either as a mono- or combination therapy. The exact indications and dosages for interferon in childhood malignancies are far from clear. Up to now, it has proved to be most efficacious in small tumour masses, providing a theoretical basis for application in minimal residual disease. Controlled clinical data, however, are not yet available. It remains to be determined whether or not interferon can be added to current chemotherapy protocols without a significant reduction of dose. Hopefully, a deeper understanding of the activities of interferon will allow us to plan better trials with combination treatments.

[Polycytemia vera in an 11-year old girl]. / Valódi polycythaemia 11 éves leányban.

The case of an 11 year old girl with three line type of polycythaemia vera, with 4 cm splenomegaly and a plethoric complexion is presented. Peripheral blood values were as follows: RBC: 7.75 x 10(12)/l, Hb: 18.8 g/l, WBC: 15.2 x 10(9)/l, platelets: 920 x 10(9)/l. Serum erythropoietin level: < 1 mU/ml. In vitro, erythroid colonies developed from the bone marrow in the absence of added erythropoetin. For three years the haematocrit value has been controlled by regular venesections. Since extreme thrombocytosis developed, the treatment was continued with interferon alpha. Different treatment protocols are discussed.

Activated clotting time versus activated partial thromboplastin time for therapeutic monitoring of heparin.

OBJECTIVE: To compare and contrast the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) for the therapeutic monitoring of heparin therapy. DATA SOURCES: Relevant articles were identified through an English-language MEDLINE search from 1966 to 1995. Additional sources were identified from the reference lists of these articles. STUDY SELECTION: Studies that investigated the use and limitations of the individual assays and those offering direct comparisons were chosen for review. DATA EXTRACTION: Features demonstrating clinical applications and limitations of the aPTT and the ACT were extracted. Where possible, data suggesting preferential application of either assay also were extracted. DATA SYNTHESIS: Both the aPTT and ACT are clinically useful for the monitoring of heparin therapy. The aPTT is used more frequently for routine monitoring; the ACT is used in specialized situations requiring large heparin doses. The ACT is typically performed at bedside and is capable of yielding results rapidly and perhaps at a lower cost than an aPTT performed by a central laboratory. Most practitioners are familiar with the central laboratory aPTT. A bedside aPTT device is available, but is not yet in widespread clinical use. Both assay techniques are subject to various limitations. CONCLUSIONS: The ACT is theoretically equally as useful as the aPTT for the routine monitoring of heparin therapy, but has not been well-studied. The ACT appears more useful in situations in which high serum concentrations of heparin are required. Further cost-effectiveness and clinical outcome studies directly comparing the ACT and the aPTT is specific clinical situations are needed.

[Menkes disease]. / A Menkes-betegség.

The Menkes or kinky hair disease is a rare, sex-linked systemic disorder of the copper metabolism. It is lethal in the first three years due to cerebral and cerebellar degeneration. Apropos of their case the authors summarise the knowledge on the diagnosis, pathogenesis and therapy.

[Progression of cutaneous T cell lymphoma in leukemia]. / Cutan T-sejtes lymphoma progressiója leukaemiába.

Transition of a (probably primary) cutaneous non-Hodgkin's lymphoma to T-stem cell leukaemia was observed in a case. Unusual clinical features, histological and laboratory data hampered the diagnosis-making of this rare disease. Using the ALL-BFM 90 HRG protocoll complete remission was achieved. Under the treatment varicella-zoster virus encephalitis took place.

[Nephropathy in patients treated with ifosfamide]. / Nephropathia ifoszfamiddal kezelt betegekben.

Between 1987-1992 in the Department of Pediatric Oncology of Child Health Center at Miskolc the appearance of nephropathy caused by high dose Ifosfamide was studied (using different protocols) in patients with childhood malignancy. From 7 patients in 5 children nephrotoxicity were developed. In consequence of Ifosfamide rickets 2 patients are given continuous bicarbonate and calcitriol substitution. The authors call attention to the frequency of Ifosfamide nephropathy, low serum bicarbonate and phosphate concentration with glucosuria, aminoaciduria and hypochloremic acidosis were the manifestations of the disturbances of renal tubular functions. Prospective monitoring of these serum and urinary abnormalities may lead to early detection of tubulopathy and allow early replacement therapy.

Effects of naltrexone pellet implantation on morphine tolerance and physical dependence in the rat.

1. The effect of naltrexone pellets containing either 10 or 30 mg of naltrexone base on the development of tolerance and physical dependence on morphine was assessed in male Sprague-Dawley rats. Tolerance-dependence on morphine was induced by s.c. implantation of six morphine pellets, each containing 75 mg morphine base for 7 days. 2. Naltrexone pellet implantation blocked the development of tolerance to the analgesic and hyperthermic effects of morphine. Similarly, naltrexone pellet implantation reversed morphine withdrawal-induced body weight loss. The effect of pellets containing 10 and 30 mg naltrexone did not differ. 3. The effect of naltrexone (10 mg) pellet implantation on various signs of naltrexone-precipitated withdrawal such as body weight loss, hypothermia and increases in urinary and fecal output was investigated. Naltrexone pellet implantation did not alter the naltrexone-precipitated withdrawal-induced body weight loss. Concurrent naltrexone pellet implantation blocked the naltrexone-precipitated withdrawal-induced hypothermia, increased fecal and urinary output in morphine-dependent rats. 4. These results indicate that a single pellet of 10 mg of naltrexone can effectively block morphine tolerance and physical dependence in the rat. Such a procedure may be useful in studying biochemical, endocrinological and immunological mechanisms involved in opioid addiction processes.

[Therapeutic problems in disseminated histiocytosis X]. / A disseminált histiocytosis X terápiás problémái.

The authors are dealing with the therapy problems of disseminated Langerhans cell histiocytosis on the basis of seven patients. In the treatment the combination of Vinblastine and Prednisolone was usually applied. The therapy was successful in four cases. The most significant prognostic factors were found to be the presence of organ dysfunction (mainly hepatic and pulmonary), the bone involvement and immunological parameters, respectively. Real therapy goals are stressed.