Nonsecretory multiple myeloma

Nonsecretory multiple myeloma (NSMM) is a rare variant of the classic form of multiple myeloma (MM) and accounts for 1% to 5% of all cases of MM. The clinical presentation and radiographic findings of NSMM and MM are the same. The diagnosis of MM requires the detection of a monoclonal gammopathy in the serum or urine. In NSMM, however, no such gammopathy can be demonstrated, making the diagnosis more difficult. We describe a 43-year-old African American woman who initially had back pain and pathologic vertebral compression fractures that were thought to be due to osteoporosis. Five months later, hypercalcemia developed and NSMM was diagnosed. No monoclonal gammopathy was found in the serum or urine, but skeletal survey showed diffuse osteolytic lesions, and bone marrow biopsy revealed marked plasmacytosis. The immunohistochemical techniques and chromosomal analysis methods that are currently available are discussed.     

Hypersensitive knockin mouse strains identify receptors and pathways for nicotine action

Two series of knockin mouse strains have been constructed with point mutations that result in hypersensitive neuronal nicotinic acetylcholine receptors containing alpha 4- or alpha 7-subunits. The full expression of the stronger alleles produces neonatal excitotoxic lethality; however, mice with attenuated expression or milder alleles are viable, and display a range of hypersensitive responses to nicotine. To date, measurements have been made on nicotine-induced seizures, Straub tail, hypothermia, antinociception, electroencephalograms and cellular electrophysiological responses. These strains are helping to define the occurrence of these important receptor subtypes, and their role in the acute and chronic actions of nicotine. The hypersensitive strains may be useful for the development of nicotinic drug therapy.     

Consanguinity and apnea of prematurity

Consanguinity, marriage between relatives, has been associated with perinatal mortality and morbidity. Apnea of prematurity is defined as the cessation of breathing for longer than 20 seconds or that of any duration if accompanied by cyanosis and sinus bradycardia, for infants born before 37 weeks of gestation. The objective of the study was to examine the association between consanguinity and apnea of prematurity in Greater Beirut, an area having a relatively high prevalence rate of consanguineous marriages. The study was cross-sectional. Between September 1, 1998, and March 31, 2001, 21723 newborn infants were admitted to the National Collaborative Perinatal Neonatal Network in Greater Beirut, Lebanon. The inclusion criteria were infants less than 37 weeks of gestation who were admitted to the intensive care unit, with no congenital malformations, sepsis, or neurologic disorders. Analysis was based on 597 infants of whom 66 had apnea of prematurity. With adjustment for weeks and type of gestation, pregnancy complications, and Apgar score, the odds ratio of apnea of prematurity for first-degree consanguineous parents as compared with other marriages was 2.9 (95% confidence interval: 1.3, 6.4). In addition to the recognized etiologic factors for apnea of prematurity, this study suggests a role played by genetic factors.     

Two ATS Recommended Protocols for Administration of Methacholine Are Not Equal

Background. The 1999 American Thoracic Society methacholine challenge guidelines stated that the 5-breath dosimeter method of methacholine administration is similar to the 2-minute tidal breath method. Recent data has disputed this assertion. We examined the differences in the diagnosis of asthma using these two methods. Methods. Data were abstracted from a prospectively generated pulmonary function database over 4 years. During the first 2 years the 5-breath dosimeter method was used, and the subsequent 2 years the 2-minute tidal breath method was used. The effect of the delivery technique was assessed by crude and adjusted odds ratios, controlling for known confounders and group differences. Results. A total of 907 subjects underwent methacholine challenge testing during the 4-year study period: 19.3% of the subjects tested with the 5-breath dosimeter method and 31.2% of those tested with the 2-minute tidal breathing method had a PC20 ≤ 8.0 mg/mL (OR 1.90, 95% CI 1.4 to 2.58, p < 0.001). The ability to reliably exclude airway hyper-responsiveness (PC20 > 16.0 mg/mL) was also altered by the differences between the testing techniques. Using the 5-breath dosimeter method, 72.4% of subjects were ruled out for airway hyper-responsiveness, whereas only 59.9% of subjects were ruled out with the 2-minute tidal breathing technique (p < 0.001). Conclusion. The two recommended protocols for the diagnosis of asthma are not equivalent and significantly alter the rate of diagnosis of asthma as well as the severity. The differences were seen across all PC20 levels, from those with strongly positive tests (PC20 ≤ 1.0 mg/mL) as well as those with negative tests for airway hyper-responsiveness (PC20 > 16.0 mg/mL).     

Effect of a novel drug-eluted balloon coated with Genistein before stent implantation in porcine coronary arteries

Background  The major drawback of stent implantation in native human coronary vessels is the occurrence of restenosis. Drug-eluting stents significantly reduce restenosis after percutaneous coronary intervention (PCI), but may be associated with persistent local inflammation involved in the restenosis mechanisms. In this setting coating coronary devices with anti-inflammatory agents represents an intriguing alternative to stent-based local drug delivery. The aim of the present study was to test in a porcine model the safety and efficacy of a novel Genistein-eluting balloon preceding coronary stenting. Design  Female piglets underwent PCI in a randomized fashion with either a Genistein-eluting or a standard balloon angioplasty, followed in all vessels by bare-metal stent implantation. Pigs were sacrificed at different time points to appraise safety (i.e. endothelialization) and efficacy (i.e. anti-inflammatory and anti-proliferative effects): 1, 4, and 6–8 weeks following PCI. Results  Overall analysis was conducted on 14 piglets. Twenty-five bare-metal stents were implanted preceded by angioplasty with a conventional balloon in 13 vessels and by the Genistein-eluted balloon in 12. No untoward effects were reported in either group. Healing and endothelialization appeared universal within 4 weeks. The Genistein-eluted balloon group disclosed a significant reduction, at four weeks from implantation, of the peri-stent inflammatory cells count (mononucleocytes 39 ± 32 Vs. 96 ± 29 per square millimetre, P = 0.019). This effect did not clearly translate into a trend towards a reduced neointimal hyperplasia at 6–8 weeks (0.13 ± 0.11 Vs. 0.14 ± 0.09, P = 0.835). Conclusion  This study provides the first in vivo demonstration of the anti-inflammatory effects of a Genistein-eluting balloon in PCI, warranting further research including the combination of a Genistein-eluting balloon with standard drug-eluting stent.