The ORF47 and ORF66 putative protein kinases of varicella-zoster virus determine tropism for human T cells and skin in the SCID-hu mouse

The varicella-zoster virus (VZV) genes ORF47 and ORF66 are predicted to encode serine/threonine protein kinases, which are homologs of herpes simplex virus 1 (HSV-1) UL13, and US3. When mutants were constructed by inserting stop codons into ORF47 and ORF66, the recombinants ROka47S and ROka66S, as well as intact ROka replicated in tissue culture. In contrast, inoculation of human thymus/liver or skin implants in SCID-hu mice showed that ORF47 protein was required for viral growth in human T cells and skin. Eliminating ORF66 expression inhibited VZV infectivity for T cells partially but did not impair replication in skin compared with ROka. Infectivity for T cells and skin was restored when ROka47S virus was complemented by insertion of ORF47 into a distant, noncoding site. The ORF47 gene product is the first VZV protein identified as necessary for T cell tropism. It also is essential for skin infectivity in vivo, as is glycoprotein C. Expression of ORF66 did not compensate for the absence of the ORF47 protein. The requirement for ORF47 expression in T cells and skin indicates that this gene product, which is dispensable in vitro, has a critical role within differentiated cells that are essential targets for VZV pathogenesis in vivo.     

Adaptation effects and reversible figures: a comment on Horlitz and O'Leary

Horlitz and O'Leary have provided further evidence for the important role of such top-down processes as attention and familiarity on reported reversals of ambiguous figures. As such, these results are consistent with the claims of several other investigators who have argued that any theory of phenomenal reversal that is based solely on passive neural processes is likely to be incomplete. However, Horlitz and O'Leary make the additional claims (1) that the several reports of adaptation effects in the literature are readily reinterpreted within an information-access framework and (2) that their own empirical work demonstrates a basic failure of neural-adaptation effects with reversible figures. It is proposed here that these claims must be viewed with caution. First, Horlitz and O'Leary's explanation for the discrepancy of their results from those of ostensibly similar experimental procedures in the reversible-figure literature is not the only, or the most likely, possibility. A plausible alternative model that posits critical procedural differences (specifically, duration of adaptation) across studies has been offered, and supporting empirical work for this latter suggestion has been presented. Second, the empirical efforts of Horlitz and O'Leary, while providing further evidence for top-down processes, do not eliminate the likely role of adaptation effects with reversible figures. There is strong reason to believe that the viewing conditions selected by these researchers may not have been sufficient to produce appreciable adaptation. Moreover, there is excellent reason to believe that both bottom-up and top-down processes moderate reported reversals of these figures.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drugs of abuse testing in a psychiatric outpatient service

Drug testing of patients in a psychiatric outpatient service is an effective way to identify patients who relapse into renewed use of drugs of abuse and in monitoring the effectiveness of ongoing medical and psychological therapy. Most of this testing involves the analysis of urine specimens with immunoassays. Hair testing affords an alternative specimen matrix that is easy to obtain and not readily adulterated and offers the advantage of a wider surveillance window. Hair analysis is technically demanding, and the possibility of false-positives caused by environmental contamination renders it a controversial alternative. Sweat and saliva are potentially useful testing matrices, but their usefulness in clinical practice must await validation by additional clinical and laboratory experience. The correct interpretation of drug test results is predicated on knowing the performance characteristics of the analytical method, route of administration, and pharmacokinetics of the drug. All questionable positive results need confirmation testing to verify true positivity.     

MR angiography of the peripheral vasculature

MR angiography (MRA) for the evaluation of peripheral arterial occlusive disease is a rapidly evolving technique. Recent prospective clinical trials have indicated that MRA may play an important role in the evaluation of patients with peripheral arterial disease. This article discusses the pertinent technical aspects and limitations of peripheral MRA as well as some of the clinical data available.     

Difference in pain relief after trigger point injections in myofascial pain patients with and without fibromyalgia

OBJECTIVE: To compare responses to trigger point (TrP) injection between patients having both myofascial pain syndrome (MPS) caused by active TrPs and fibromyalgia syndrome (FMS) and patients with MPS due to TrPs but without FMS. DESIGN: Prospective design blinded measurement, before- after trial. SETTING: A pain control medical clinic. PATIENTS: Group 1: MPS + FMS; Group 2: MPS only. All patients (9 in each group) had active TrPs in the upper trapezius muscle. INTERVENTION: Myofascial TrP injection with 0.5% xylocaine. MAIN OUTCOME MEASURES: Subjective pain intensity (PI), pain threshold (PT), and range of motion (ROM) were assessed before, immediately after, and 2 weeks after TrP injection. RESULTS: In a comparison of preinjection measures to immediate postinjection measures, only ROM was significantly improved (p < .05) in Group 1 patients; all three parameters were significantly improved (p < .05) in the Group 2 patients who had only MPS. Two weeks after injection, both groups showed significant improvement (p < .05) in all three measured parameters as compared to preinjection measurements. In a comparison of the two groups, the immediate effectiveness of TrP injection was significantly less (p < .05) in Group 1 than in Group 2 for all three parameters. Two weeks after injection, the degree of improvement in PT or ROM (but not PI) was not significantly different between two groups. Postinjection soreness (different from myofascial pain) was more severe, developed sooner, and lasted longer in Group 1 than in Group 2. CONCLUSION: Trigger point injection is a valuable procedure for pain relief for patients in both group. Patients with FMS are likely to experience significant but delayed and attenuated pain relief following injection of their active TrPs compared to myofascial pain patients with similar TrPs but without FMS. Also, FMS patients are likely to experience significantly more postinjection soreness for a longer period of time.     

Risk factors for cardiovascular disease in Latina women

Cardiovascular disease is the leading cause of death for Latina women in the United States. Nevertheless, the literature available about the risk factors for cardiovascular disease is inconsistent and hampered by issues related to race and ethnic identification and the exclusion of Latina women from major population-based studies. Compared with white women, Latina women have more of the major and contributing factors for cardiovascular disease, including hypertension, diabetes, overweight/obesity and physical inactivity. This article presents an overview of the literature on cardiovascular disease in Latina women. Literature on mortality, as well as key risk factors (hypertension, cigarette smoking, elevated serum lipids, overweight and obesity, diabetes mellitus and physical inactivity) are reviewed. Issues related to the sociocultural environment of Latina women are also discussed. The article concludes with the implications for clinical practice and further nursing research. The information provided in this article may help nurse clinicians, educators and researchers design and implement nursing interventions that can promote heart health and prevent cardiovascular disease in Latina women.     

Cytopathological analysis of sputum in patients with airflow obstruction and significant smoking histories

Advances in the understanding of lung cancer biology have led to observations that specific genetic changes occur in premalignant dysplasia. These observations have occurred predominantly in molecular studies of resected lung tumors and consequently, they may not be fully representative of those biological abnormalities characterizing premalignant lesions in individuals without overt lung cancer. Studies of premalignant epithelial cell biology and chemoprevention are needed in this patient subgroup. Such an initiative is now underway through the lung cancer Specialized Program of Research Excellence (SPORE) grant awarded to the University of Colorado Cancer Center (and affiliated institutions) by the National Cancer Institute. To identify participants for the early detection and chemoprevention trials of the Colorado SPORE, we initiated a sputum cytology screening program targeting persons with chronic obstructive pulmonary disease and smoking histories of 40 or more pack-years. During the first 26 months after activation of the screening program, sputum samples from 632 participants were evaluated. Of these, 533 (84%) of the subjects submitted specimens deemed adequate for cytopathological interpretation; 99 (16%) provided sputum samples unsuitable for cytodiagnosis. Of those participants who submitted adequate samples, 48% had cytodiagnoses of mild dysplasia, 26 % had moderate to severe dysplasia, and 2% presented with carcinoma in situ or invasive carcinoma. Logistic regression modeling was pursued to determine whether selected demographic and/or clinical status variables could be identified as statistically significant predictors of the specific cytological outcome to be expected (mild dysplasia, moderate dysplasia, and so forth). The only apparent associations found from both univariate and multivariate analyses were that the total number of pack-years of smoking history decreased with severity of cytodiagnosis and that those individuals with mild or moderate dysplasia were more likely to be ex-smokers than those with grades of regular metaplasia or lower. Based on the initial results of the Colorado SPORE sputum cytology screening program, we conclude that persons with chronic obstructive pulmonary disease and 40 or more pack-years of smoking history have a high prevalence of premalignant dysplasia detectable through sputum cytology and should be targeted for research programs focusing on lung cancer prevention, early detection, and exploratory biomarker studies.     

Rectal trauma: management based on anatomic distinctions

Principles of rectal wound management, including routine diversion, injury repair, presacral drainage and distal washout, evolved from World War II and the Vietnam conflict and have been questioned in recent years. We believe significant confusion arises because of imprecise definition of injury location relative to retroperitoneal involvement. Our 5-year experience with penetrating rectal injuries at a Level I trauma center was analyzed. Injuries to the anterior and lateral surfaces of the upper two-thirds of the rectum were classified as intraperitoneal (IP, serosalized), and those of the posterior surface extraperitoneal (EP, no serosa); injuries to the lower one-third were EP. A total of 58 injuries were managed (92% gunshot wounds). Of these, 16 were IP, and 42 had some EP component. Ten patients underwent repair without diversion (6 IP, 4 EP); there were no leaks. Ten septic complications occurred in the remaining population: 2 necrotizing fasciitis, 5 abdominal abscess, and 3 presacral infections (PIs) (2 presacral abscesses and 1 wound tract infection). PI is the only complication that can be specifically associated with EP rectal injuries relative to management; as associated injury confounds interpretation of the other complications. The operative management in the 38 patients with diverted EP wounds with respect to presacral infection (PI) demonstrated the following: repair injury (n = 10), 0 PI versus no repair (n = 28), 3 PI (P = 0.55); washout (n = 33), 2 PI versus no washout (n = 5), 1 PI (P = 0.35); presacral drain (n = 30), 1 PI versus no drain (n = 8), 2 PI (P = 0.11). We conclude that most IP injuries can be managed with primary repair. EP wounds to the upper two-thirds of the rectum should usually be repaired. EP wounds to the lower one-third, which are explored and repaired, do not require drainage. EP wounds that are not explored should be managed with presacral drainage to minimize the incidence of presacral abscess.     

Genetic susceptibility to head and neck cancer: interaction between nutrition and mutagen sensitivity

The development of head and neck cancer may depend not only on exposure to environmental carcinogens but also on a genetically based susceptibility to carcinogen-induced damage. This thesis presents a case-control study that demonstrates the significance of mutagen sensitivity, a measure of an individual's intrinsic DNA repair capacity against free radical damage, as a risk factor for the disease. As part of the case-control analysis, 167 previously untreated patients and 177 age- and sex-matched healthy controls were assessed for various lifestyle factors including tobacco and alcohol habits, occupational exposures, and diet. Mutagen sensitivity expressed by each individual was determined by quantifying bleomycin-induced chromosomal breaks within peripheral blood lymphocytes in vitro. Consistent with our initial observations and those of others, mutagen hypersensitivity was strongly associated with increased risk of head and neck cancer (odds ratio, 4.95; 95% confidence interval, 2.67 to 9.17) after adjusting for age, sex, and race. Low intake of vitamins C and E was also associated with an increased risk of disease and was interactive with mutagen sensitivity in risk estimates. Individuals with both a low intake of various antioxidants and increased chromosomal sensitivity to oxidant-induced DNA damage were at greatest risk. This study supports the concept that the risk of head and neck cancer is determined by a balance of factors that either enhance or protect against free radical oxygen damage, including innate capacities for DNA repair.