IgG4-Related Disease and Hypertrophic Pachymeningitis

Hypertrophic pachymeningitis (HP) is an inflammatory condition in which the dura mater of the cranium or spine becomes thickened, leading to symptoms that result from mass effect, nerve compression, or vascular compromise. The differential diagnosis of HP includes immune-mediated conditions such as rheumatoid arthritis and vasculitis, malignancies, and infections. Many times, no diagnosis is reached; in such cases, the disease has been described as idiopathic HP. IgG4-related disease (IgG4-RD) is a recently described inflammatory condition known to cause tumefactive lesions at myriad anatomical locations. Both IgG4-RD and idiopathic HP share similar demographics, histopathology, and natural history. We hypothesized that IgG4-RD is a common cause of idiopathic HP.To investigate this hypothesis, we identified all pathology specimens diagnosed as noninfectious HP during 25 years at our institution. Fourteen cases had stained slides and paraffin blocks to permit review of the original hematoxylin and eosin stained slides as well as immunostaining of cell blocks. Recently published consensus guidelines describing characteristic histopathology and the necessary quantity of IgG4+ plasma cell infiltrate were used to diagnose IgG4-RD.Four cases (66.6%) that had been regarded previously as representing idiopathic HP were diagnosed as IgG4-RD; of all the reviewed cases, IgG4-RD represented 29% of cases. Of the remaining cases, 3 cases were associated with granulomatosis with polyangiitis (GPA), 2 with lymphoma, and 1 each with rheumatoid arthritis, giant cell arteritis, and sarcoidosis. Two of the cases could not be diagnosed more precisely and were classified as undifferentiated HP. Clinical history, serologic tests, cerebrospinal fluid studies, and radiology alone could not identify the cause of HP. Rather, biopsy with histopathology and immunostaining was necessary to reach an accurate diagnosis. Significant IgG4+ plasma cell infiltrates were observed in rheumatoid arthritis, granulomatosis with polyangiitis, and lymphoma, underscoring the importance of histopathology in making the diagnosis of IgG4-RD.This case series demonstrates that IgG4-RD may be the most common etiology of noninfectious HP and highlights the necessity of biopsy for accurate diagnosis.Abbreviations: ANCA = antineutrophil cytoplasmic antibodies, CNS = central nervous system, CSF = cerebrospinal fluid, CT = computed tomography, GPA = granulomatosis with polyangiitis, HP = hypertrophic pachymeningitis, HPF = high-power field, IgG4-RD = IgG4-related disease, MRI = magnetic resonance imaging, WBC = white blood cell     

Human T and natural killer cells possess a functional renin-angiotensin system: further mechanisms of angiotensin II-induced inflammation

The renin-angiotensin system (RAS) plays an important role in the regulation of inflammation and in the progression of chronic kidney disease. Accumulation of inflammatory cells into the renal parenchyma has been a hallmark of chronic kidney disease; however, little is known concerning the presence and the function of RAS elements in T and natural killer (NK) cells. Here is reported a co-stimulatory effect of angiotensin II (AngII) by showing an augmentation of mitogen and anti-CD3-stimulated T and NK cell proliferation with AngII treatment. Angiotensinogen and AngI also generated the same effect, suggesting that NK and T cells have functional renin and angiotensin-converting enzyme activity. Indeed, they express renin, the renin receptor, angiotensinogen, and angiotensin-converting enzyme by mRNA analysis. Flow cytometric analysis and Western blot revealed angiotensin receptor 2 (AT(2)) expression in T and NK cells, whereas AT(1) expression was found in T and NK cells and monocytes by Western blot. These receptors were shown to be functional in calcium signaling, chemotaxis, and proliferation. However, AT(1) and AT(2) antagonists alone or in combination were unable to abrogate completely the effects of AngII, suggesting that another AngII receptor may also be functional in leukocytes. This is the first study to show that T and NK cells are fully equipped with RAS elements and are potentially capable of producing and delivering AngII to sites of inflammation. Because their chemotaxis is enhanced by AngII, this creates a potential inflammatory amplification system.     

Importance of donor- and recipient-derived selectins in cardiac allograft rejection

The selectins expressed on activated endothelial cells (E- and P-selectin), leukocytes (L-selectin), and platelets (P-selectin) play crucial roles in the rolling and tethering of leukocytes. We explored the importance of donor and recipient selectins in acute and chronic cardiac allograft rejection using mice deficient in all three selectins (ELP-/-). In BALB/c recipients, survival of fully allomismatched hearts from ELP-/- C57BL/6 donors was almost double that of wild-type grafts. In ELP-/- cardiac allografts, mononuclear cell infiltration and vasculitis of intramyocardial coronary arteries were significantly reduced. Interestingly, ELP-/- grafts were rejected similarly in both the presence and the absence of recipient selectins, and both wild-type and ELP-/- recipients promptly rejected wild-type hearts. Alternative adhesive molecules such as alpha4beta7 integrin may compensate for the lack of selectins and may mediate rejection in ELP-/- recipients. Chronic rejection was evaluated in a major histocompatibility complex (MHC) class II mismatch model using C57BL/6.C-H2(bm12) mice. While lack of selectins in recipients did not offer protection against chronic rejection, luminal stenosis of coronary arteries in ELP-/- grafts was markedly diminished. In conclusion, donor-derived selectins contribute to the development of both acute and chronic cardiac allograft rejection, and targeting donor selectins may open novel therapeutic approaches in clinical transplantation.     

Treatment of non-small cell lung cancer in the older patient

Lung cancer is a disease of the elderly, with a median age at diagnosis of 70 years. However, there is a dearth of good quality evidence to guide treatment in this population and most of the data are extrapolated from younger patients. Current research is directed toward establishing simplified instruments to quantify fitness of older patients for various forms of therapy. Although current evidence suggests that outcomes after standard therapy are similar to those seen in younger patients, older patients have an increased incidence of adverse events. Until better predictive markers are available to guide treatment, therapy should be individualized using available instruments, including a comprehensive geriatric assessment. If an older patient is deemed to be fit, it is reasonable to use the treatment options recommended for younger individuals. This article summarizes the available data on the treatment of non-small cell lung cancer in the older patient.     

Management of squamous cell carcinoma of the head and neck in the elderly: Review and recommendations

In general, the management and reported outcomes for elderly patients with squamous cell carcinoma of the head and neck (SCCHN) have been similar to those of younger patients. But older adults are a distinct subpopulation of patients who differ from younger patients due to their increased risks for: comorbidities, decreased functional status, a potential decline in cognitive function and an increase in vulnerabilities. Older adults have been underrepresented in the clinical trials which define our best treatment strategies. This review explores the evidence used to establish common practice in managing SCCHN and evaluates the relevance of this evidence for the older adult, concluding with recommendations based on the review.     

Effect of a noise reduction program on a medical-surgical unit

This quasi-experimental study tested an intervention to reduce sound levels in an acute care hospital. A parallel pre- and posttest design with control group was used; patients and employees completed the Topf Adapted Sound Disturbance Scales, and environmental sound levels were recorded on a Quest 2900 Sound Level Meter. Treatment interventions included an educational PowerPoint presentation for employees, minor environmental acoustical alterations, and the use of a Quest 261 Sound Detector/Controller for behavioral modification. None of these interventions produced statistically significant changes in sound levels. Patients and employees reported slightly less disturbance due to noise postintervention on the treatment unit. The findings of this study support Philbin and Gray's suggestion that the use of sound-absorbing materials in the hospital's physical structure may be the most effective measure to reduce sound levels in the hospital setting.     

Intravenous levodopa administration in humans based on a two-compartment kinetic model

Levodopa, when combined with a decarboxylase inhibitor, essentially delivers dopamine directly to the brain, with no net effect on brain blood vessels. For future neuroimaging studies of Parkinson disease and Tourette syndrome, we sought to rapidly produce a biologically relevant levodopa concentration in plasma and then maintain that concentration long enough to assess motor, cognitive, emotional, and neuroimaging responses, while minimizing side effects in levodopa-naive individuals. Based on available pharmacokinetic data and a two-compartment model, we designed a decreasing-exponential-rate infusion to meet these goals. This report gives results of double-blind levodopa and placebo infusions in six healthy subjects. Mean plasma levodopa concentrations were within 3% of their 1200 ng/mL target at 20 and 40 min into the infusion, and within 20% between approximately 12 and 90 min. Levodopa significantly reduced serum prolactin and raised serum growth hormone concentrations. Volunteers had no significant side effects.