Degenerative disc disease (DDD) is a chronic process that can become clinically manifest in multiple disorders such as idiopathic low back pain, disc herniation, radiculopathy, myelopathy, and spinal stenosis. The limited available technology for the treatment of these and other pathologic and disabling conditions arising from DDD is highly invasive (eg, surgical discectomy and fusion), manifesting a certain degree of complications and unsatisfactory clinical outcomes. Although the precise pathophysiology of DDD remains to be clearly delineated, the progressive decline in aggrecan, the primary proteoglycan of the nucleus pulposus, appears to be a final common pathway. It has been hypothesized that imbalance in the synthesis and catabolism of certain critical extracellular matrix components can be mitigated by the transfer of genes to intervertebral disc cells encoding factors that modulate synthesis and catabolism of these components. The successful in vivo transfer of therapeutic genes to target cells within the intervertebral disc in clinically relevant animal models of DDD is one example of the rapid progress that is being made towards the development of gene therapy approaches for the treatment of DDD. This chapter reviews the ability of gene therapy to alter biologic processes in the degenerated intervertebral disc and outlines the work needed to be done before human clinical trials can be contemplated.
Pink salmon, Oncorhynchus gorbuscha, is the main salmon species of commercial importance in Prince William Sound. Unlike other Pacific salmon, they have a two-year life cycle and have adapted to spawn in the intertidal reaches of numerous small streams throughout the oil-spill area. Thus, they represent the species at highest potential risk for spill-related injury. This paper discusses results of field programs initiated within a few days of the spill and designed to assess spill effects on critical early life stages of pink salmon in postspill years. Samples of water and stream sediments from throughout the spill area were used to define the exposure of pink salmon to residual hydrocarbons from the spill. Mean sediment concentrations of polycyclic aromatic hydrocarbons (PAH) up to 300 ppb were measured in oiled streams in 1989 and generally followed a downward trend toward background in 1990 and 1991. These PAH concentrations were then used in regression analyses of potential effects on key early life stages of pink salmon. Water samples taken from both nearshore feeding and rearing areas and offshore migratory areas show that hydrocarbon concentrations were from one to four orders of magnitude lower than concentrations reported in the literature to cause acute or chronic effects on fish species. The postspill field and laboratory studies of pink salmon early life stages included examination of potential effects on 1989, 1990, and 1991 eggs, fry, and juveniles. Generally high survival, ranging from 77% to 100%, was observed in both oiled and reference streams in 1989, and a weak correlation was indicated with stream sediment PAH at only one of the three tide levels sampled (12 feet). In 1990, egg viability was 90.6% from reference streams and 91.1% from oiled streams, as determined through incubation studies. Mean condition index, kD, was 1.76 for fry from reference streams and 1.79 from oiled streams, indicating normal developmental timing. Study results show that no substantial effects on critical early life stages of pink salmon in Prince William Sound are attributable to the spill. Results of incubation experiments with eggs from the spill-affected area provide no indication of sterility or abnormal development. Our results are consistent with the pink salmon returns in 1990 and 1991 that yielded returns over three times the size of the parental year class.
This paper presents results of a field program designed to monitor the status of wildstock pink salmon populations in Prince William Sound following the Exxon Valdez oil spill. Field counts of spawning salmon were conducted each year from 1989 through 1992 to test for spill effects on the distribution and abundance of pink salmon adults spawning in selected streams in the southwestern portion of Prince William Sound, including streams from the most heavily oiled areas. Counts of whole-stream and intertidal escapement density were statistically compared for 40 study streams in 1989 and for a subset of those streams in successive years. Measurements of residual hydrocarbons were made from stream-bed sediments to test for correlations with spawning behavior. Adult pink salmon in the postspill years of 1990 and 1991, progeny of the year classes considered most vulnerable to the oil spill, returned in high numbers, with the wildstock spawners exceeding their parent year returns. In 1989, adult returns reflected the relatively weak run for that year with a mean spawner density of 0.68 fish/m2 in reference streams and 0.69 fish/m2 in oiled streams. In 1990, mean escapement density for reference streams was 1.40 fish/m2 and 1.55 fish/m2 for oiled streams, indicating the strongest run of the four study years. Trends in polycyclic aromatic hydrocarbon (PAH) concentrations for the majority of oiled streams show a general decline from 1989 to background levels by 1990. The measured PAH concentrations indicate low-level exposure to residual hydrocarbons that have not produced detectable differences in spawning behavior or escapement between streams from oiled areas compared with unoiled streams. In Part 1 of this paper, elements of the early lifestage survival of potentially affected year classes of pink salmon were examined by Brannon et al. (this volume). Conclusions indicate measures of early lifestages were largely indistinguishable between oiled and unoiled streams. The early lifestage data, in combination with observations of the strength of postspill returns and analyses of escapement reported herein, are the basis for the conclusion that changes in the wildstock pink salmon population in Prince William Sound could not be attributed to the oil spill.
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