Resonant-mass detectors of gravitational radiation.

A network of second-generation low-temperature gravitational radiation detectors is nearing completion. These detectors, sensitive to mechanical strains of order 10(-18), are possible because of a variety of technical innovations hat have been made in cryogenics, low-noise superconducting instrumentation, and vibration isolation techniques. Another five orders of magnitude improvement in energy sensitivity of resonant-mass detectors is possible before the linear amplifier quantum limit is encountered.

Refractory hypercalcemia in an infant secondary to talc pleurodesis resolving after renal transplantation.

Talc pleurodesis is the definitive therapy of recurrent pneumothorax and has not been associated with metabolic complications. We report an anephric male infant who developed severe hypercalcemia 6 months following talc pleurodesis for recurrent peritoneal dialysis-related hydrothorax. The etiology of hypercalcemia was related to persistently elevated 1,25-dihydroxyvitamin D(3) (1,25[OH]2D) levels. The source appeared to be the extrarenal production of 1,25(OH)2D from macrophages in a large thoracic talc granuloma. Hypercalcemia was controlled with a combination of a low calcium diet, low calcium dialysis, ketoconazole and hydroxychloroquine, but elevated 1,25(OH)2D levels persisted. At 32 months of age the child underwent renal transplantation with alemtuzumab pre-conditioning. The hypercalcemia resolved immediately, with normalization of serum 1,25(OH)2D levels and without hypercalciuria. This case demonstrates that hypercalcemia is a potential complication of talc pleurodesis from the extrarenal production of 1,25(OH)2D and that alemtuzumab, a monoclonal antibody directed against the CD52 antigen (which is expressed on almost all macrophages), may have a role in the treatment of hypercalcemia associated with granulomatous conditions.

Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial.

PURPOSE: To evaluate the effects of oral N-acetylcysteine (NAC), which replenishes systemic glutathione, on decreasing inflammation and improving lung function in CF airways. METHODS: A multicenter, randomized, double-blind proof of concept study in which 70 CF subjects received NAC or placebo orally thrice daily for 24 weeks. ENDPOINTS: primary, change in sputum human neutrophil elastase (HNE) activity; secondary, FEV(1) and other clinical lung function measures; and safety, the safety and tolerability of NAC and the potential of NAC to promote pulmonary hypertension in subjects with CF. RESULTS: Lung function (FEV(1) and FEF(25-75%)) remained stable or increased slightly in the NAC group but decreased in the placebo group (p=0.02 and 0.02). Log(10) HNE activity remained equal between cohorts (difference 0.21, 95% CI -0.07 to 0.48, p=0.14). CONCLUSIONS: NAC recipients maintained their lung function while placebo recipients declined (24 week FEV1 treatment effect=150 mL, p<0.02). However no effect on HNE activity and other selected biomarkers of neutrophilic inflammation were detected. Further studies on mechanism and clinical outcomes are warranted.

Human bronchial epithelial cells secrete laminin 5, express hemidesmosomal proteins, and assemble hemidesmosomes.

Epithelial cells attach to the basement membrane through adhesive contacts between the basal cells of the epithelium and the proteins of the extracellular matrix (ECM). The hemidesmosome (HD) is a specialized cell-ECM contact, that mediates the attachment of the epithelial cell basal surface to the ECM. In bronchial epithelial cells, the protein components that constitute the HD have not been demonstrated. Using immunohistochemical techniques, we determined that normal human bronchial epithelial (NHBE) cells express the HD cell surface integrin alpha6beta4 and produce laminin 5, the ECM protein associated with HDs. Furthermore, expression of the HD-associated structural proteins, bullous pemphigoid antigens 1 (BPAG 1) and 2 (BPAG 2), was demonstrated in NHBE cells by immunofluorescence microscopy and immunoblot analyses. In addition, we confirmed the presence of laminin 5 in the basement membrane (BM) of bronchial epithelial biopsy specimens and of BP230, BP180, and the alpha6beta4 integrin heterodimer at the site of bronchial epithelial cell-ECM interaction in vivo. Finally, using electron microscopy, we were able to demonstrate intact HDs in a glutaraldehyde-fixed NHBE cell monolayer. These findings suggest that bronchial epithelium forms HDs and that the laminin 5-alpha6beta4 integrin interaction may be important in stabilizing epithelial cell adhesion to the BM in the lung.

Primary Sjogren syndrome: clinical and immunopathologic features.

Primary Sjogren syndrome is an autoimmune condition in which dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) result from lymphocytic infiltration of lacrimal and salivary glands. Clinical and laboratory features of 60 primary Sjogren syndrome patients seen at our clinic during the past three years are presented. These patients illustrate the wide spectrum of extraglandular features that may occur as a result of lymphoid infiltration of lung, kidney, skin, stomach, liver, and muscle. They further emphasize the difficulty in classifying a patient as primary or secondary Sjogren syndrome (ie, sicca symptoms associated with systemic lupus erythematosus, rheumatoid arthritis, or scleroderma), particularly early in the disease course. As an initial step in understanding the pathogenesis, the lymphocytes that infiltrate the salivary glands and lymph nodes were characterized by using monoclonal antibodies that recognize distinct lymphocyte subsets and by using in vitro functional assays. These studies have demonstrated that affected tissues have infiltrates of T cells with helper/inducer activity and with a high frequency of "activation antigens." The immunohistologic techniques are useful in differentiating "benign" and "pseudolymphoma" lesions (both due predominantly to T cells) from non-Hodgkin lymphoma (usually due to B-cell infiltrates). Although there is no "cure" for primary Sjogren syndrome patient's symptoms may be significantly improved by measures aimed at prevention of ocular and dental complications and by the recognition of extraglandular features that may be amenable to specific treatment.

Ocular reticulum cell sarcoma. Presentation as retinal detachment with demonstration of monoclonal immunoglobulin light chains on the vitreous cells.

A 61-year-old man with a history of cerebral reticulum cell sarcoma-microglioma (histiocytic lymphoma) in remission was initially seen with uveitis and exudative retinal detachment. Pars plana vitreous biopsy established the diagnosis by cytologic findings and allowed the immunofluorescent demonstration of a monoclonal immunoglobulin within the vitreous cells. Direct immunofluorescent microscopy of the vitreous infiltrate may prove to be of benefit in the workup of patients with uveitis in whom malignant lymphoma must be excluded.

Endogenous Candida endophthalmitis leading to bilateral corneal perforation.

A premature neonate developed advanced bilateral endophthalmitis before the significance of underlying Candida sepsis was appreciated. Severe endophthalmitis resulted in corneal thinning, descemetocele formation, and perforation. The infection occurred in the clinical setting of broad-spectrum antibiotic therapy and indwelling intravenous catheters. Cultures of blood and catheter tips had been positive for Candida but were not considered significant until advanced ocular infection was noted. The septic process resulted in the infant's death after systemic amphotericin B therapy was discontinued because of renal toxicity.

Subretinal neovascular membrane and disciform scar in Behçet's disease.

A 33-year-old woman with a three-year history of aphthous ulceration of the mouth, vaginal ulceration, and erythema nodosum, also had a subretinal neovascular membrane in the left eye. She showed antibodies to guinea pig lip epithelium by indirect immunofluorescence. Thus, Behçet's disease must also be considered in the differential diagnosis of subretinal neovascular membrane in young patients, especially when antibodies to oral mucosa can be shown.

Ozone effects on the immediate-phase response to allergen in the nasal airways of allergic asthmatic subjects.

Epidemiologic and clinical trials have suggested that exposure to ozone increases airway hyperresponsiveness and inflammatory response to inhaled nasal allergen challenge in allergic asthmatic subjects. Previous studies have demonstrated an increased late-phase response to nasal allergen challenge; however, the early-phase response is unknown. We sought to characterize the early-phase response by measuring mast-cell inflammatory mediators and cellular influx at time points immediately following ozone exposure and subsequent allergen challenge. A cohort of mild, asymptomatic dust mite--sensitive asthmatic subjects was identified. Each subject underwent two separate exposures to both 0.4 ppm ozone and clean air in a randomized manner. Nasal lavage was performed before and after each exposure. Nasal allergen was then administered to a defined clinical end point, followed by nasal lavage. Differential cell counts and mast-cell products were identified in each lavage specimen. The mast-cell mediators tryptase and prostaglandin D2 were analyzed, as was a marker of epithelial cell permeability, albumin. Although allergen produced an increase in early-onset mediator release (mast cell-derived), no enhancement was noted after exposure to ozone. Neutrophil and eosinophil inflammatory mediators were not increased after ozone exposure or enhanced after allergen exposure, although ozone did enhance eosinophilic influx after exposure to allergen. Ozone exposure does not promote early-phase--response mediator release or enhance the response to allergen challenge in the nasal airways of extrinsic asthmatic subjects. Ozone, however, may promote an inflammatory cell influx, which helps induce a more significant late-phase response in this population.

Ocular and oral problems in arthritis. How to recognize, when to refer.

Recognition of oral and ocular problems is important in the management of arthritis. Although the focus of attention is usually on joint problems, patients with these chronic disorders require a comprehensive approach to their total medical care. Physicians need to watch for physical signs of significant inflammation and should alert their patients to watch for significant symptoms.

Adverse drug reaction reporting: a working system.

Adverse drug reactions (ADRs) are a severe problem. Up to 30% of hospitalized medical patients may have an ADR, and up to 5% of hospitalizations may be caused by an ADR. Reporting systems that track these reactions vary widely as to their capture rates. In a 12-month period, with the aid of the Medical Record Department at St. Elizabeth Hospital Medical Center, 150 adverse drug reactions were catalogued. Fifty-eight of these resulted in admission, while 92 occurred during hospitalization. Cardiovascular agents and antibiotics produced the most reports. Reactions are evaluated and tabulated by the Department of Pharmacy, and subsequently presented to the Pharmacy (P&T) Committee as part of the quality assurance program, which meets the standards mandated by the Joint Commission on Accreditation of Hospitals. The reporting system is described in this article.

Approaches to the treatment of Sjögren's syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by complaints of sicca symptoms (dry eye and mouth) and can be associated with other autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, etc). As a result, SS can be difficult to diagnose. Currently, there are several criteria standards for SS, including the San Diego criteria and the European Study Group criteria. According to the San Diego criteria, the incidence of SS is about 0.5%, whereas for the European Study Group it ranges from 3% to 5%. This almost 10-fold difference in SS incidence has led to confusion for both the clinician and researcher. The tearing reflex involves a neural loop in which afferent nerve signals from the ocular surface are relayed centrally to the medulla. The input from the afferent nerves is then processed and sent back via efferent nerves stimulating blood vessels and secretory glands to provide and pump water for tears. Immune factors, such as cytokines, have a profound effect on the tearing mechanism by damaging secretory glands and releasing antibodies to influence the response of muscarinic M3 receptors. Thus, the interaction of neural and immune factors affects the secretory response of glands and contributes to the pathogenesis of SS sicca symptoms. The recent development of muscarinic agonists, such as pilocarpine and cevimeline, serves an important step in recognizing the interaction between the immune and neuroendocrine systems.

American Society of Transplantation executive summary on pediatric lung transplantation.

Lung transplantation in children poses distinctly different challenges from those seen in the adult population. This consensus statement reviews the experience in the field of pediatric lung transplantation and highlights areas that deserve further investigation.

Red eye unresponsive to treatment.

Red eyes that fail to respond quickly and completely to topical antibiotic treatment require more extensive evaluation to relieve the symptoms and avert possible sight-threatening complications. The initial differential diagnosis of red eye, which includes iritis, acute glaucoma, keratitis and corneal ulcer, and rarer disorders, must be reexamined. A commonly misdiagnosed cause of red eye is the dry eye syndrome. As a primary or secondary problem, the dry eye syndrome must be treated appropriately to avert sight-threatening complications and to alleviate substantial discomfort. The dry eye syndrome may represent the presenting sign of Sjögren's syndrome or it may be due to medication use, with important systemic and ocular implications.