Clinical picture of Pneumocystis jiroveci pneumonia in cancer patients

BACKGROUND: Pneumocystis pneumonia (PCP) is common in patients with HIV infection but may also occur in patients with other causes of immunodeficiency, including hematologic and solid malignancies. METHODS: To better describe the clinical picture of PCP as to maintain a high level of suspicion in adequate cases, we studied 56 cancer patients with PCP and compared them to 56 cancer patients with bacterial pneumonia. RESULTS: Among 56 PCP patients, 44 patients (78.6%) had hematologic malignancies (18 recipients of bone marrow transplantation) and 12 patients had solid tumors. The time since diagnosis was 24 months (range, 4 to 49 months). All patients with solid tumors and 20 patients (45.4%) with hematologic malignancies were receiving steroids. Only six patients were receiving PCP prophylaxis. The main symptoms were fever (85.7%), dyspnea (78.6%), and cough (57.1%). Time from symptom onset was 7 days (range, 3 to 14 days). PCP presented as severe pneumonia (Pao(2), 58 mm Hg [range, 50 to 70 mm Hg]) with bilateral interstitial infiltrates (80.4%) and bilateral ground-glass attenuation (89.3%) by CT. Of the 24 ICU patients (42.9%), 16 patients (19.6%) required mechanical ventilation. Eleven patients (19.6%) died. Compared to 56 patients with bacterial pneumonia, PCP patients were more likely to have non-Hodgkin lymphoma and be receiving long-term steroids; they had longer times since diagnosis, longer symptom duration, higher frequencies of fever and of diffuse lung disease (diffuse crackles, bilateral infiltrates, and hypoxemia), higher frequency of ground-glass opacities, and lower frequency of pleural involvement. CONCLUSIONS: PCP presents as subacute, febrile, hypoxemic, and diffuse pulmonary involvement in patients with solid tumors or hematologic malignancies receiving long-term steroids.     

Discrepant effects of inducible nitric oxide synthase modulation on systemic and splanchnic endothelial nitric oxide synthase activity and expression in cirrhotic rats

BACKGROUND: Arterial vasodilatation, which is a major factor in the pathogenesis of the hyperkinetic circulatory state and portal hypertension in cirrhosis, is due to arterial nitric oxide (NO) overproduction secondary to endothelial NO synthase (eNOS) and inducible NOS (iNOS) upregulation. However, in cirrhosis, the respective roles of eNOS and iNOS isoforms in NO overproduction are still unknown and the effect of iNOS modulation on eNOS activity and expression has not been evaluated in the systemic or splanchnic vessels. The aim of this study was to evaluate the effects of modulating aortic and superior mesenteric arteries (SMA) iNOS on arterial eNOS activity and expression in rats with cirrhosis. METHODS: eNOS and iNOS protein expression and eNOS activity (assessed by its phosphorylation at serine 1177) were measured in the aortas and SMA in untreated and treated cirrhotic rats with lipopolysaccharide (LPS), N-iminoethyl-L-lysine (L-NIL), a selective iNOS inhibitor, and LPS plus L-NIL. RESULTS: LPS administration significantly increased eNOS and iNOS protein expression and eNOS activity in the aortas of both sham-operated and cirrhotic rats. However, in SMA, LPS administration induced a decrease in eNOS protein expression and activity and an increase in iNOS protein expression. CONCLUSION: The results of this study may explain the worsening of the hyperdynamic state in cirrhosis during septic shock by direct LPS-induced eNOS activation in large systemic vessels, and its inhibition in concomitant small splanchnic vasculature by iNOS synthesized NO.     

IFNgamma and antibody responses among French nurses during a tuberculosis contact tracing investigation

Study

A comparative study which compared PPD skin testing inserted according to the French Society of Pneumology's recommendations and interferon gamma release assay (IGRA) (QuantiFERON^® TB Gold In-tube, QF–TB–IT, Cellestis, Carnegie, Australia) was performed during a tuberculosis contact investigation in our hospital.

Patients

Nineteen French health-care workers (HCWs) volunteered to participate. All of the HCW enrolled were BCG vaccinated and had a normal chest X-ray at entry.

Results

Among the HCW, 68.4% were TST positive. By comparison, only 31.6% had a positive QF-TB-IT result. We took advantage of the negative tube and the corresponding plasma for antibody detection by ELISA. None were ELISA positive. Fourteen HCWs were followed up. None of the HCWs accepted a course of antiTB chemoprophylaxis. Despite the difficulty in establishing a trend in kinetics, we saw the complexity of interpretation of a dynamic T-cell response after contact with an index case.

Conclusion

This initial and first French picture provides us with the observation that only 44% of TST-positive HCW were IGRA positive, and the IGRA test allowed the detection of LTBI in two TST negative HCWs.     

Monoclonal antibodies in hematological malignancies: past, present and future

Much progress has been made during the last few decades in the treatment of hematological malignancies. Monoclonal antibodies (MoAbs) represent a major advance toward a targeted therapy that can dramatically improve the antitumor effect with a substantial reduction of toxicity derived from therapy. Unlike many small molecules, MoAbs offer unique target specificity. Several MoAbs are now in clinical use for hematologic malignancies therapy, and many others are currently undergoing clinical evaluation. This review summarizes the state-of-the-art MoAbs treatment, beginning with an overview of the scientific background to their synthesis, mechanism of action and choice of target antigen, mainly focusing on those antibodies that are currently in use in clinical practice. Despite these advances, significant challenges remain in the identification of optimal cellular targets, antibody forms and treatment schedules for therapeutic applications.     

Therapeutic plasma exchange in Casablanca

BACKGROUND: Therapeutic plasma exchange (TPE) is an extracorporeal blood purification method for the treatment of diseases in which pathological proteins have to be eliminated. In the aim to demonstrate our single center activity, we analyzed our data since 2 years. METHODS: Between years 2002 and 2005, 104 TPE procedures were performed on 42 patients. Median age and male/female ratio were 32 (range, 17-56) and 24/18, respectively. Departments those referred the majority of the TPE were neurology (n=32), nephrology (n=5) and intensive care unit (n=5). The most common indications were: polyradiculoneuropathies (53%), myasthenia gravis (17%) and Guillain-Barré syndrome (12%). RESULTS: The median TPE procedure per patient was 2.3 (range, 1-10). In the majority of patients, vascular access was provided by puncture of two large, durable peripheral antecubital veins. The procedures were performed with the "Haemonetic Ultralight" discontinuous flow cell separator devices. Citrate solution was used as an anticoagulant in all cases. The substitution fluids most often used in our unit are Albumin 20% solution (92 times), Albumin 4% (10 times) and fresh frozen plasma (twice). Seventy five percent of the patients showed improvement, 7% remained the same and 18% worsened. Thirteen adverse reactions were recorded. CONCLUSION: The creation of a national registry by the local society is a vital move to improve TPE practice in our country.     

Reproducibility of bone mineral density measurements using dual X-ray absorptiometry in daily clinical practice

Bone mineral density (BMD) measurements are frequently performed repeatedly for each patient. Subsequent BMD measurements allow reproducibility to be assessed. Previous studies have suggested that reproducibility may be influenced by age and clinical status. The purpose of the study was to examine the reproducibility of BMD by dual energy X-ray absorptiometry (DXA) and to investigate the practical value of different measures of reproducibility in three distinct groups of subjects: healthy young volunteers, postmenopausal women and patients with chronic rheumatic diseases. Two hundred twenty-two subjects underwent two subsequent BMD measurements of the spine and hip. There were 60 young healthy subjects, 102 postmenopausal women and 60 patients with chronic rheumatic diseases (33 rheumatoid arthritis, 10 ankylosing spondylitis and 10 other systemic diseases). Forty-five patients (75%) among the third group were receiving corticosteroids. Reproducibility was expressed as the smallest detectable difference (SDD), coefficient of variation (CV), least significant change (LSC) and intraclass correlation coefficient (ICC). Sources of variation were investigated by linear regression analysis. The median interval between measurements was 0 days (range 0–7). The mean difference (SD) between the measurements (g/cm²) was –0.0001 (±0.003) and –0.0004 (±0.002) at L1-L4 and the total hip, respectively. At L1-L4 and the total hip, SDD (g/cm²) was ±0.04 and ±0.02, CV (%) was 2.02 and 1.29, and LSC (%) 5.60 and 3.56, respectively. The ICC at the spine and hip was 0.99 and 0.99, respectively. Only a minimal difference existed between the groups. Reproducibility in the three groups studied was good. In a repeated DXA scan, a BMD change, the least significant change (LSC) or the SDD should be regarded as significant. Use of the SDD is preferable to use of the CV and LSC because of its independence from BMD and its expression in absolute units. Expressed as SDD, a BMD change of at least ±0.04 g/cm² at L1-L4 and ±0.02 g/cm² at the total hip should be considered significant. This reproducibility seems independent from age and clinical status and improved in the hips by measuring the dual femur.     

Bone Mineral Density of the Spine and Femur in Healthy Moroccan Women

Bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry (DXA) are widely used to diagnose osteoporosis and assess its severity. Previous studies show the necessity to establish reference data for bone mass measurements for each particular population. Such data are lacking for the Moroccan population. The aim of this study was to determine spine and femur BMD reference values for the Moroccan female population and to compare them with values from western and other Arab countries. A cross-sectional study of 569 Moroccan women, (randomly selected in the area of Rabat, the capital of Morocco, aged between 20 and 79 yr) was carried out to establish reference values of BMD. Measurements were taken at the lumbar spine and proximal femurs using DXA (Lunar Prodigy Vision, GE). The data were compared with published normative data taken by United States (U.S.), European, Kuwaiti, Lebanese, and Saudi women over 6 decades of age. The percentage of osteoporosis in postmenopausal women using our reference curve was compared to that observed when the other curves (US, European and Arab) implemented in the Lunar machine was used. Our results showed that the Moroccan women showed the expected decline in BMD at both sites with age after peaking at 20–29 years of age. Moroccan females have lower BMD at the spine than U.S., Europeans, and Kuwaitis (approximately 10–12% for patients older than 50 yr). The BMD values of the total femur in Moroccan females were close to western (European and American), and Kuwaitis, but higher than Lebanese and Saudis. Using our reference database, 37.9% of postmenopausal women had spine osteoporosis vs. 39.6% and 23.4% using US/European and Arabic Lunar reference values respectively. At the femurs, 6.7% had osteoporosis vs. 2.5% using the Arabic Lunar reference values. In conclusion, our study emphasizes the importance of using population-specific reference values for BMD measurements to avoid over or underdiagnosis of osteoporosis.     

New methods for inferring population dynamics from microbial sequences.

The reduced cost of high throughput sequencing, increasing automation, and the amenability of sequence data for evolutionary analysis are making DNA data (or the corresponding amino acid sequences) the molecular marker of choice for studying microbial population genetics and phylogenetics. Concomitantly, due to the ever-increasing computational power, new, more accurate (and sometimes faster), sequence-based analytical approaches are being developed and applied to these new data. Here we review some commonly used, recently improved, and newly developed methodologies for inferring population dynamics and evolutionary relationships using nucleotide and amino acid sequence data, including: alignment, model selection, bifurcating and network phylogenetic approaches, and methods for estimating demographic history, population structure, and population parameters (recombination, genetic diversity, growth, and natural selection). Because of the extensive literature published on these topics this review cannot be comprehensive in its scope. Instead, for all the methods discussed we introduce the approaches we think are particularly useful for analyses of microbial sequences and where possible, include references to recent and more inclusive reviews.