Inhibition of the expression of lysyl oxidase and its substrates in cadmium-resistant rat fetal lung fibroblasts.

Copper (Cu)-dependent lysyl oxidase (LO) catalyzes crosslinking of collagen and elastin stabilizing the extracellular matrix (ECM). Chronic inhalation of cadmium (Cd), a toxic metal, induces emphysema. To probe mechanisms of Cd injury to the lung, we developed Cd-resistant (CdR) cells from rat fetal lung fibroblasts (RFL6) by chronic exposure to CdCl(2) from 1 to 40 microM and further examined their expressions of LO, LO substrates, and Cu-scavenging thiols. Levels of cellular thiols, metallothionein, and glutathione in CdR cells were elevated to 13.0- and 3.2-fold of parental controls, respectively, whereas LO mRNA and protein levels were markedly reduced in these cells, with catalytic activity declining to only 16% of the parental control. A conspicuous 52 kDa species rather then the normal 50 kDa proenzyme appeared in the CdR cell extract but not in the conditioned medium, which was codistributed with the endoplasmic reticulum marker [DiOC5(3)] within the cell, implying the Cd-induced 52 kDa species as a product of an abnormal LO-processing defect in secretion. Addition of Cu into CdR cell cultures enhanced the expression of LO mRNA, protein and catalytic activities reflecting limitation of Cu bioavailability for LO in these cells. With inhibition of LO, CdR cells also displayed downregulation of collagen and elastin, substrates of LO. Restoration of collagen synthesis by exposure of CdR cells to purified LO or Cu suggests that inhibition of LO and limitation of Cu cofactor by Cd, as key phenotype changes, accelerated collagen and elastin damage, a critical event pertinent to emphysema pathogenesis.     

Handcuff neuropathies

Compressive neuropathy due to tight application of handcuffs occurred in 5 patients. The superficial radial nerve was affected in 8 hands and the median nerve in two. Neurologic deficits persisted as long as 3 years after handcuffing. Nerve conduction studies helped to exclude malingering and other diagnoses. All patients had been intoxicated when handcuffed or had been arrested with force. The handcuff mechanism, which allows accidental overtightening after application, is an unrecognized factor in these neuropathies.     

Uveal melanoma radiation. 125I brachytherapy versus helium ion irradiation

The optimum radiation therapy for uveal melanoma is uncertain. Both helium ion irradiation and 125I brachytherapy have been used to treat this neoplasm. This investigation analyzed the control and complication rates of uveal melanomas treated with helium ions of 125I plaques. In both a retrospective and a prospective dynamically balanced study, the control rates appeared to be similar. There were more posterior segment complications after 125I plaques and more anterior segment complications, including neovascular glaucoma, after helium ion irradiation. The follow-up period is too short to draw definitive conclusions on the radiation complications. Overall, approximately 89% of eyes were retained and less than 4% of treated eyes were removed because of failure to control the tumor.     

Managing self-injection difficulties in patients with relapsing-remitting multiple sclerosis.

Difficulties with self-injection, including inabillity to self-inject, are common for individuals taking home-administered injectable medications. In relapsing-remitting multiple sclerosis (MS), all of the currently available disease-modifying medications are injectables marketed for self-injection. Problems with self-injection pose a barrier to treatment adherence for many patients. Clinicians at the University of California, San Francisco (UCSF) Multiple Sclerosis Center have developed a number of strategies to help patients who experience anxiety associated with self-injection. These strategies have been empirically tested and found to be effective and easily implemented by mental health professionals and nurses. This article offers case examples and discussion of the principles of the techniques developed at UCSF to remediate patients' difficulties with self-injection. Nurses are most often the healthcare providers responsible for training MS patients in self-injection and monitoring their compliance. Nurses who are familiar with these tools have the opportunity to have a significant positive impact on patient comfort, confidence, and, ultimately, successful long-term adherence to disease-modifying medications.     

Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.