Faris G. Bakri

Invasive filamentous fungal infections in allogeneic hematopoietic stem cell transplant recipients after recovery from neutropenia: clinical, radiologic, and pathologic characteristics.

Invasive filamentous fungal infection (IFFI) is an important cause of mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We reviewed 22 consecutive cases of IFFI in allogeneic HSCT recipients at Roswell Park Cancer Institute. IFFI was diagnosed after neutrophil recovery in 21 patients (95%). All had received corticosteroids within 1 month prior to IFFI diagnosis. Fourteen (64%) presented with dyspnea, and only 7 (32%) were febrile. Aspergillus species were isolated in 18 (82%) cases. Thirty day mortality after IFFI diagnosis was associated with a higher mean daily dose of corticosteroids (P = 0.02) and receiving OKT3 (P = 0.01) within 1 month prior to IFFI diagnosis and serum creatinine >2 mg/dl at the time of diagnosis (P = 0.004). Histopathologic material from biopsy or autopsy was available in 15 patients (68%). In 8 (53%), the predominant lung histopathology was an acellular coagulative necrosis and hyphal angioinvasion was observed in some of these cases. These findings have generally been observed in neutropenic patients but not in non-neutropenic HSCT recipients. The predominance of coagulative necrosis in our series may reflect the high doses of corticosteroids used to treat graft-versus-host disease (GVHD), which may have disabled leukocyte trafficking and hyphal killing.

Systemic and Mucosal Antibody Response to Moraxella catarrhalis after Exacerbations of Chronic Obstructive Pulmonary Disease

To characterize the immune response to Moraxella catarrhalis after exacerbations of chronic obstructive pulmonary disease (COPD), pre- and postexacerbation serum and sputum supernatant samples obtained during 21 exacerbations in 18 patients were studied, using the homologous infecting isolates. New serum immunoglobulin G (IgG) detected by whole-cell enzyme-linked immunosorbent assay developed after 12 (57.1%) of 21 exacerbations. Analysis of serum samples with flow cytometry, which detects antibodies that are exclusive to epitopes on the bacterial surface, revealed that 5 (23.8%) of the 21 exacerbations were associated with the development of new serum IgG to surface epitopes. Three of these serum samples and 2 other serum samples contained new IgG directed at lipooligosaccharide. Flow cytometry revealed that new mucosal IgA to surface-exposed epitopes of the infecting isolate developed in sputum supernatants after 42% of exacerbations. Therefore, adults with COPD develop variable humoral immune responses to M. catarrhalis after exacerbations, including new serum IgG and new mucosal IgA to epitopes on the bacterial surface.

Invasive Pulmonary Filamentous Fungal Infection in a Patient Receiving Inhaled Corticosteroid Therapy

We report a case of invasive pulmonary filamentous fungal infection in a patient with chronic obstructive pulmonary disease who was treated with a conventional dose of inhaled fluticasone in the absence of other causes of immunosuppression. This case demonstrates the potential risk for opportunistic fungal infections in patients treated with high-potency lipophilic inhaled corticosteroids.

Respiratory syncytial virus infection in the late bone marrow transplant period: report of three cases and review.

Respiratory syncytial virus (RSV) infection is an important cause of respiratory mortality in immunosuppressed patients, including bone marrow transplant (BMT) recipients. The presence of lower respiratory tract infection and infection in the pre-engraftment phase of BMT is believed to confer a poor prognosis. Three patients who underwent allogeneic BMT at our institution developed RSV pneumonia over 1 year post BMT, with the underlying disease in remission. All three were hypoxic with extensive pulmonary disease at presentation. Treatment consisted of aerosolized ribavirin and intravenous immune globulin with successful clearing of viral shedding and excellent clinical outcomes. RSV infection is probably less severe in the late post-BMT period, but needs to be considered early in the differential diagnosis of pulmonary infiltrates in this patient population. Bone Marrow Transplantation (2001) 27, 1071–1073.

Heparin Inhibits Reactive Oxygen Species Generation by Polymorphonuclear and Mononuclear Leucocytes

To examine the hypothesis that heparin may affect leukocyte function and that it may have anti-inflammatory properties, we investigated the effect of heparin on reactive oxygen species (ROS) generation by leucocytes. Heparin was injected intravenously at a dose of 10000 units into eight normal subjects. Blood samples were collected from the antecubital vein sequentially, prior to and following heparin at 0, 0.5, 1, 2, and 4 hours. ROS generation was inhibited significantly by polymorphonuclear cells (PMNL) at 0.5, 1, and 2 hours and returned to baseline level at 4 hours. Similarly, ROS generation was inhibited markedly by mononuclear cells (MNC) at 0.5 hours, with a peak inhibition at 1 hour; it returned to baseline level by 4 hours. The maximum inhibition of ROS generation by PMNL was 57.3+/-19% of the basal, while that by MNC was 56.4+/-11% of the basal. Since ROS are proinflammatory and cause tissue damage, it is possible that heparin may have an anti-inflammatory effect in vivo, apart from its antithrombotic effect. Since ROS also bind to nitric oxide (NO) and reduce the bioavailability of NO, heparin may indirectly increase the bioavailability of NO and thus act as a vasodilator. This effect of heparin may be of particular relevance to its use in unstable angina and following thrombolysis in acute myocardial infarction in preventing reperfusion injury.

First report of clinical, functional, and molecular investigation of chronic granulomatous disease in nine Jordanian families.

IntroductionChronic granulomatous disease is a rare inherited immunodeficiency syndrome caused by mutations in four genes encoding essential nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex components.Material and methodsClinical, functional, and molecular investigations were conducted in 15 Jordanian CGD patients from nine families.Results and DiscussionFourteen patients were children of consanguineous parents and suffered from autosomal recessive (AR) CGD forms with mutations in the CYBA, NCF1, and NCF2 genes encoding p22phox, p47phox, and p67phox proteins, except for one patient in whom the mutation’s location was not found. One patient had an extremely rare X+CGD subtype resulting from a novel missense mutation (G1234C) in exon 10 of CYBB. We found a genetic heterogeneity in the Jordanian families with a high frequency of rare ARCGD, probably because consanguineous marriages are common in Jordan. No clear correlation between the severity of the clinical symptoms and the CGD types could be established.

Griscelli syndrome type 2: a rare and lethal disorder.

Griscelli syndrome is a rare autosomal recessive disorder. It is characterized by pigment dilution and variable immune deficiency leading to increased susceptibility to certain infections and a tendency to develop a life-threatening hemophagocytic syndrome known as the accelerated phase. Griscelli syndrome is now classified into 3 types based on the genetic and molecular features. Primary neurological presentation without the accelerated phase is rare in type 2. In this article, the authors report a boy who was presented with seizures and diffuse white matter involvement unaccompanied by the other features of the accelerated phase. Mutation analysis in family members revealed the presence of a missense mutation in Rab27a gene. In addition to the rare presentation, this is the first case of Griscelli syndrome to be reported from Jordan.

Orofacial findings in chronic granulomatous disease: report of twelve patients and review of the literature

BackgroundChronic granulomatous disease is an extremely rare primary immunodeficiency syndrome that can be associated with various oral complications. This can affect high number of patients. However, data on oral complications is sparse. Here we will review the literature and describe the orofacial findings in 12 patients.FindingsThe age range was 5-31 years. Oral findings were variable, and reflected a low level of oral hygiene. They included periodontitis, rampant caries, gingivitis, aphthous-like ulcers, and geographic tongue. One patient had white patches on the buccal mucosa similar to lichen planus. Another patient had a nodular dorsum of the tongue associated with fissured and geographic tongue. Biopsies from the latter two lesions revealed chronic non-specific mucositis. Panoramic radiographs showed extensive periodontitis in one patient and periapical lesions in another patient.ConclusionPatients with chronic granulomatous disease may develop oral lesions reflecting susceptibility to infections and inflammation. It is also possible that social and genetic factors may influence the development of this complication. Therefore, oral hygiene must be kept at an optimum level to prevent infections that can be difficult to manage.

Persistent bacteraemia due to methicillin-resistant Staphylococcus aureus with reduced susceptibility to vancomycin in a patient with erythrodermic psoriasis

A 49-y-old male with erythrodermic psoriasis developed persistent bacteraemia for 3 months due to methicillin-resistant Staphylococcus aureus despite antimicrobial therapy. The skin was the likely focus. Three consecutive isolates from the blood and 1 from the nose were identical and had vancomycin MIC of 4 mg/l.

Brucella glomerulonephritis resulting in end-stage renal disease: a case report and a brief review of the literature

Brucella glomerulonephritis is a rare condition with only a few reported cases. We review the literature, and describe a 24-year-old female who presented with edema and proteinuria. Blood grew Brucella melitensis. Renal biopsy showed diffuse proliferative glomerulonephritis. The patient progressed to end-stage renal disease despite antibiotic and steroid therapy.