Hypogammaglobulinaemia after rituximab treatment-incidence and outcomes.

BACKGROUND: Rituximab, a chimeric monoclonal antibody against CD20, is increasingly used in the treatment of B-cell lymphomas and autoimmune conditions. Transient peripheral B-cell depletion is expected following rituximab therapy. Although initial clinical trials did not show significant hypogammaglobulinaemia, reports of this are now appearing in the literature. METHODS: We performed a retrospective review of patients previously treated with rituximab that were referred to Clinical Immunology with symptomatic or severe hypogammaglobulinaemia. Patient clinical histories, immunological markers, length of rituximab treatment and need for intravenous immunoglobulin replacement therapy (IVIG) were evaluated. An audit of patients receiving rituximab for any condition in a 12-month period and frequency of hypogammaglobulinaemia was also carried out. RESULTS: We identified 19 post-rituximab patients with persistent, symptomatic panhypogammaglobulinaemia. Mean IgG level was 3.42 ± 0.4 g/l (normal range 5.8-16.3 g/l). All patients had reduced or absent B-cells. Haemophilus Influenzae B, tetanus and Pneumococcal serotype-specific antibody levels were all reduced and patients failed to mount an immune response post-vaccination. Nearly all of them ultimately required IVIG. The mean interval from the last rituximab dose and need for IVIG was 36 months (range 7 months-7 years). Of note, 23.7% of 114 patients included in the audit had hypogammaglobulinaemia. CONCLUSION: With the increasing use of rituximab, it is important for clinicians treating these patients to be aware of hypogammaglobulinaemia and serious infections occurring even years after completion of treatment and should be actively looked for during follow-up. Referral to clinical immunology services and, if indicated, initiation of IVIG should be considered.

White mulberry (Morus alba) foliage methanolic extract can alleviate Aeromonas hydrophila infection in African catfish (Clarias gariepinus).

Two experiments were simultaneously conducted with Morus alba (white mulberry) foliage extract (MFE) as a growth promoter and treatment of Aeromonas hydrophila infection in separate 60 and 30 days trail (Experiments 1 and 2, resp.) in African catfish (Clarias gariepinus). In Experiment 1, four diets, control and control supplemented with 2, 5, or 7 g MFE/kg dry matter (DM) of diet, were used. In Experiment 2, fish were intraperitoneally infected with Aeromonas hydrophila and fed the same diets as experiment 1 plus additional two diets with or without antibiotic. Results of experiment 1 showed that growth was unaffected by dietary levels of MFE. Treatments with the inclusion of MFE at the levels of 5 and 7 g/Kg DM had no mortality. Red blood cells (RBC), albumin, and total protein were all higher for the treatments fed MFE (5 and 7 g/Kg DM). Results of experiment 2 showed RBC, hemoglobin, hematocrit, globulin, albumin, and total protein improved with the increase in MFE in the infected fish. The dietary MFE at the level of 7 g/kg DM reduced mortality rate. In conclusion, MFE at the level of 7 g/kg DM could be a valuable dietary supplement to cure the infected fish.

A review on the vascular features of the hyperimmunoglobulin E syndrome.

Autosomal recessive, autosomal dominant and the sporadic forms of hyperimmunoglobulin E syndrome (HIES) are multi-system disorders. Although HIES patients may present with cold abscesses, the vascular features of HIES are not well recognized. The objective of this review is to characterize the nature and spectrum of vascular abnormalities in HIES patients. Vascular abnormalities in HIES patients were reviewed with Medline and Google Scholar-based searches. In brief, the searches combined terms related to HIES with the terms related to vasculature. Furthermore, reference lists from the original studies and review papers identified were screened. There were vascular abnormalities in 25 patients with HIES. These abnormalities were identified as aneurysms (coronary, aortic, carotid and cerebral), pseudoaneurysms, congenital patent ductus venosus, superior vena cava syndrome, vasculitides, vascular ectasia, thrombosis and others. They may be congenital or acquired, in the veins and arteries, affecting both sexes. These abnormalities can be seen in all subtypes of HIES. They could be also fatal in children and adults. Limited pathological investigations revealed the presence of vasculitis. Three of the patients were found to have overlap diseases. In this review, the spectrum of vascular abnormalities in HIES are documented and discussed in detail for the first time. They highlight a previously under-recognized and potentially devastating complication of these disorders. These vascular abnormalities constitute one of the major clinical characteristics in HIES. The presence of hypereosinophilia, vasculitis and defective angiogenesis in HIES may contribute to the formation of vascular abnormalities in HIES.

Dangerous liaison: sexually transmitted allergic reaction to Brazil nuts.

Brazil nuts are the second most frequent cause of nut allergy in the United Kingdom. We report the case of a 20-year-old woman with documented Brazil nut allergy who developed widespread urticaria and mild dyspnea after intercourse with her boyfriend who had earlier consumed Brazil nuts. Skin prick testing with the boyfriend's semen after Brazil nut consumption confirmed significant reactivity whereas a sample before nut consumption was negative. We believe this to be the first case of a sexually transmitted allergic reaction.

Prolonged survival after resection and radiotherapy for solitary brain metastases from non-small-cell lung cancer.

Selected patients with brain metastases from non-small-cell lung cancer benefit from aggressive treatment. This report describes three patients who developed solitary brain metastases after previous resection of primary adenocarcinoma of the lung. Each underwent surgical resection of their brain metastasis followed by cranial irradiation and remain disease free 10 or more years later. Two patients developed cognitive impairment approximately 8 years after treatment of their brain metastasis, which was felt to be due to their previous brain irradiation. Here we discuss the treatment of solitary brain metastasis, particularly the value of combined method approaches in selected patients and dose-volume considerations.

Knowledge-based grouping of modeled HLA peptide complexes.

Human leukocyte antigens are the most polymorphic of human genes and multiple sequence alignment shows that such polymorphisms are clustered in the functional peptide binding domains. Because of such polymorphism among the peptide binding residues, the prediction of peptides that bind to specific HLA molecules is very difficult. In recent years two different types of computer based prediction methods have been developed and both the methods have their own advantages and disadvantages. The nonavailability of allele specific binding data restricts the use of knowledge-based prediction methods for a wide range of HLA alleles. Alternatively, the modeling scheme appears to be a promising predictive tool for the selection of peptides that bind to specific HLA molecules. The scoring of the modeled HLA-peptide complexes is a major concern. The use of knowledge based rules (van der Waals clashes and solvent exposed hydrophobic residues) to distinguish binders from nonbinders is applied in the present study. The rules based on (1) number of observed atomic clashes between the modeled peptide and the HLA structure, and (2) number of solvent exposed hydrophobic residues on the modeled peptide effectively discriminate experimentally known binders from poor/nonbinders. Solved crystal complexes show no vdW Clash (vdWC) in 95% cases and no solvent exposed hydrophobic peptide residues (SEHPR) were seen in 86% cases. In our attempt to compare experimental binding data with the predicted scores by this scoring scheme, 77% of the peptides are correctly grouped as good binders with a sensitivity of 71%.

Structures of two novel crystal forms of Naja naja naja phospholipase A2 lacking Ca2+ reveal trimeric packing.

Three crystal forms of Naja naja naja phospholipase A2 were discovered through random crystallization screening, including two heretofore uncharacterized forms. The crystallization conditions for both of these novel crystal forms are Ca(2+)-free whereas previously reported conditions include Ca2+. One of the new crystal forms has a cubic lattice in the space group P2(1)3 (a = b = c = 69.24 A), the other has an orthorhombic lattice in the space group P2(1)2(1)2(1) (a = 67.22 A, b = 73.48 A, c = 87.52 A) and a previously characterized crystal belong to the tetragonal space group P4(3)2(1)2 (a = b = 88.6 A, c = 107.4 A). The structure from the cubic crystal form has been determined to 1.8 A and refined to an R-factor of 17% while the structure from the orthorhombic form has been determined to 2.65 A and has been refined to an R-factor of 21%. The determination of the cubic structure extends the resolution to which structures of this molecule have been determined from 2.3 A to 1.8 A. The two newly determined structures, in combination with the previously determined structure, generate an informative structural ensemble from which structural changes due to Ca2+, which is required for catalysis, and the effect of crystal contacts on side-chain conformations and oligomeric association can be inferred. Both of the newly determined structures reveal a trimeric oligomer as observed in the tetragonal structure; this appears to be a unique feature of the Naja naja naja enzyme.

Optimizing sweet potato [Ipomoea batatas (L.) Lam.] root and plantlet formation by selection of proper embryo developmental stage and size, and gel type for fluidized sowing.

Potassium starch polyacrylamide, potassium acrylate, a copolymer of potassium acrylate and acrylamide, and hydroxyethylcellulose carrier gels were tested to find a fluid drilling material suited for synthetic seeding of sweet potato (Ipomoea batatas (L.) Lam.) somatic embryos. Somatic embryo developmental stage and size, and maturation (incubation) time were also evaluated to improve plantlet formation. All embryos suspended in the fluidized hydroxyethylcellulose gel were viable after six days and 7% developed into plantlets after two weeks. Up to 97% of the somatic embryos suspended in acrylate and/or acrylamide gels died within six days. Root development was at least 10% and plantlet development at least 30% greater when embryos were subcultured on basal medium for 16 instead of 25 days prior to placement and suspension in hydroxyethylcellulose gel. Up to 25% more plantlets were obtained from embryos at the elongated torpedo stage than those at the cotyledonary or torpedo stages of development. When suspended in hydroxyethylcellulose gel embryo length had no effect on the percentage of plantlets obtained.

An outbreak of cutaneous leishmaniasis in Guyana: epidemiology, clinical and laboratory aspects.

An outbreak of cutaneous leishmaniasis reached epidemic proportions among military personnel in Guyana during the period from November, 1977 to March, 1980. As the patients presented from widely separated areas of the hinterland it is likely that cutaneous leishmaniasis is endemic throughout the virgin tropical rain forest of Guyana, although infection is normally sporadic. A striking clinical feature was the 'spirotrichoid' involvement of the draining lymphatics and nodes in half the cases, which histologically all came from the middle region of the spectrum (groups II, III or IV of Ridley's 1980 classification). All the cases tested were serologically positive to a Leishmania braziliensis antigen. One hundred and ten patients were successfully treated with pentamidine, with minimal side-effects, but some required a second course. Four relapsed patients all belonged to the same histological group.