Diffuse Lung Disease in Neurofibromatosis

Prevalence, characteristics and the very existence of neurofibromatosis-associated diffuse lung disease remain unclear, mostly because the few studies that looked at pulmonary involvement in such patients used chest X-ray as diagnostic mean. We report on the clinical, functional and HRCT findings in a patient with neurofibromatosis-associated diffuse lung disease and provide a short literature review.     

Constitutively released adenosine diphosphate regulates proplatelet formation by human megakaryocytes

Background

The interaction of adenosine diphosphate with its P2Y₁ and P2Y₁₂ receptors on platelets is important for platelet function. However, nothing is known about adenosine diphosphate and its function in human megakaryocytes.

Design and Methods

We studied the role of adenosine diphosphate and P2Y receptors on proplatelet formation by human megakaryocytes in culture.

Results

Megakaryocytes expressed all the known eight subtypes of P2Y receptors, and constitutively released adenosine diphosphate. Proplatelet formation was inhibited by the adenosine diphosphate scavengers apyrase and CP/CPK by 60-70% and by the P2Y₁₂ inhibitors cangrelor and 2-MeSAMP by 50-60%, but was not inhibited by the P2Y₁ inhibitor MRS 2179. However, the active metabolites of the anti-P2Y₁₂ drugs, clopidogrel and prasugrel, did not inhibit proplatelet formation. Since cangrelor and 2-MeSAMP also interact with P2Y₁₃, we hypothesized that P2Y₁₃, rather than P2Y₁₂ is involved in adenosine diphosphate-regulated proplatelet formation. The specific P2Y₁₃ inhibitor MRS 2211 inhibited proplatelet formation in a concentration-dependent manner. Megakaryocytes from a patient with severe congenital P2Y₁₂ deficiency showed normal proplatelet formation, which was inhibited by apyrase, cangrelor or MRS 2211 by 50-60%. The platelet count of patients with congenital delta-storage pool deficiency, who lack secretable adenosine diphosphate, was significantly lower than that of patients with other platelet function disorders, confirming the important role of secretable adenosine diphosphate in platelet formation.

Conclusions

This is the first demonstration that adenosine diphosphate released by megakaryocytes regulates their function by interacting with P2Y₁₃. The clinical relevance of this not previously described physiological role of adenosine diphosphate and P2Y₁₃ requires further exploration.Key words: ADP, proplatelet formation, P2Y13 receptor     

Membranous glomerulonephritis secondary to allogeneic stem cell transplant: review of the literature

Renal injury associated with hematopoietic stem cell transplant (HSCT) may be related to a combination of factors. Chronic graft-versus-host disease (cGVHD) is the most common complication of allogeneic HSCT. Although the kidneys are not considered the primary target organs for GVHD, chronic impairment of renal function may occur in 20% to 60% of HSCT patients. Membranous glomerulonephritis (MG) is the most frequent renal complication observed in patients who develop nephrotic syndrome after allogeneic HSCT. In this setting, the pathogenesis of MG is not clearly understood and the most appropriate treatment approach has not been established. In order to summarize the current knowledge on this issue, a review of the pertinent literature has been performed. The available data on MG diagnosed in patients submitted to allogeneic HSCT were identified using the MEDLINE database (last accessed: Jan 30, 2012). Fifty-nine patients with allogeneic HSCT-related MG with a median age of 43 years were identified. MG occurred at a median time of 17 months after allogeneic HSCT. A history of acute or concomitant clinically apparent cGVHD was present in 69% and 31% of cases, respectively. cGVHD, nonmyeloablative conditioning regimens, immunosuppression withdrawal, and the use of peripheral blood stem cell grafts were identified as risk factors. Among the 53 patients with available outcome data, complete remission, partial response, and inefficacy of treatment were recorded in 65%, 22% and 13% of cases, respectively. MG after allogeneic HSCT seems to be etiologically related to subclinical or overt cGVHD, which flares up after discontinuation of immunosuppression. The available measures can induce sustained long-term remission in about two-thirds of affected patients.     

Age-related differences in lower extremity tissue compartments and associations with physical function in older adults

The lower extremities are important to performing physical activities of daily life. This study investigated lower extremity tissue composition, i.e. muscle and fat volumes, in young and older adults and the relative importance of individual tissue compartments to the physical function of older adults. A total of 43 older (age 78.3 ± 5.6 years) and 20 younger (age 23.8 ± 3.9 years) healthy men and women participated in the study. Older participants were further classified as either high- (HF) or low-functioning (LF) according to the Short Physical Performance Battery (SPPB). Magnetic resonance images were used to determine the volumes of skeletal muscle, subcutaneous fat (SAT), and intermuscular fat (IMAT) in the thigh (femoral) and calf (tibiofibular) regions. After adjusting for the sex of participants, younger participants had more femoral muscle mass than older adults (p < 0.001 for between group differences) as well as less femoral IMAT (p = 0.008) and tibiofibular IMAT (p < 0.001). Femoral muscle was the only tissue compartment demonstrating a significant difference between the two older groups, with HF participants having 31% more femoral muscle mass than LF participants (mean difference = 103.0 ± 34.0 cm³; p = 0.011). In subsequent multiple regression models including tissue compartments and demographic confounders, femoral muscle was the primary compartment associated with both SPPB score (r² = 0.264, p = 0.001) and 4-meter gait speed (r² = 0.187, p = 0.007). These data suggest that aging affects all lower extremity compartments, but femoral muscle mass is the major compartment associated with physical function in older adults.     

Aortic arch patch aortoplasty for Ortner's syndrome in the age of endovascular stented grafts

We present a case of hoarseness in a 68-year-old man with a post-traumatic saccular aortic arch aneurysm, effort dyspnea, and dysphonia. Oropharyngeal examination and flexible nasal endoscopy revealed left vocal fold palsy, with the left fold lying in the paramedian position. On account of these and other findings, we made the diagnosis of Ortner's syndrome. We treated the patient surgically by endoluminal repair with a Dacron patch. The postoperative course was uneventful. No additional procedure was necessary on the vocal folds, since he showed prompt postoperative speech improvement.We believe that an accurate evaluation should be made before switching a patient to endovascular treatment. Our case shows that careful preoperative planning, coupled with the most recent cerebral protection techniques, can enable a safe and straightforward surgical solution to a complex anatomic problem.