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Multifactorial analysis of long-term follow-up (more than 5 years) of primary extremity sarcoma.

BACKGROUND: The majority of survival studies in patients with extremity soft tissue sarcoma have focused on early recurrence and mortality. There are few data addressing long-term follow-up and survival. OBJECTIVE: To analyze survival and recurrence in patients with extremity soft tissue sarcoma who survive for more than 5 years. METHODS: Patients who underwent treatment for primary tumors (July 1982 to July 1994) and were followed up for more than 5 years were the subject of study. Disease-specific and disease-free survival were determined actuarially. Significance was evaluated using log-rank testing for univariate analysis and Cox model stepwise regression for multivariate analysis. RESULTS: A total of 495 patients with primary extremity tumors were treated before July 1989 and eligible for 5-year follow-up. Of these, 282 have been followed up for more than 5 years (median follow-up, 84.4 months). Actuarial disease-specific survival of patients who survive for longer than 5 years was 79%+/-7% (+/-SEM) at 10 years, and of those who were metastasis free at 5 years was 91%+/-4% at 10 years. On univariate analysis, post-5-year disease-specific survival was influenced by positive microscopic margin and initial tumor size of 5 cm or greater. On multivariate analysis, post-5-year disease-specific survival was influenced only by positive margins. CONCLUSIONS: Based on these analyses, 21% of patients with primary extremity sarcoma who survive for 5 years will die of disease within 5 years. Even of those who are metastasis free at 5 years, 9% will die of disease within 5 years. In contrast to early mortality, tumor grade has no influence on post-5-year prognosis. Patients with positive microscopic margins are at risk for post-5-year disease-specific mortality and therefore require long-term follow-up and consideration for investigational therapy.

Disease-Free Survival↗

Localized, operable soft tissue sarcoma of the lower extremity.

Recent developments in adjuvant treatment of soft tissue sarcomas of the extremities have altered the surgical approach to this disease. To assess the effects of changing management on local recurrence rates and to examine factors governing local failure, we reviewed the records of 315 adults with operable, nonmetastatic soft tissue sarcoma of the lower extremity who were treated at one institution over a ten-year period. The median follow-up was 8.2 years. One third of our patients presented with locally recurrent tumors after initial treatment elsewhere. Sixty-six percent of the lesions were above the knee, and 60% were high grade. Two thirds of the patients underwent limb-sparing surgery (LSS), which in the latter half of the study period outnumbered amputations by four to one. Local recurrence was directly related to the adequacy of the surgical margins. Adjuvant radiotherapy and chemotherapy did not significantly decrease local recurrence in patients who underwent LSS, although favorable trends were observed. A significantly increased risk of local failure was associated with age greater than 53 years, presentation with local recurrence, high tumor grade, deep location, positive nodes, and less than adequate surgical margins. Local failure also varied significantly with histologic type and was highest in patients with embryonal rhabdomyosarcoma and neurofibrosarcoma. Improved local control, particularly in patients with high-grade tumors, was observed in the latter half of the study period despite the increased use of LSS. When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of local failure: age greater than 53 years, presentation with local recurrence, high grade, less than adequate margins, embryonal rhabdomyosarcoma, and neurofibrosarcoma. The key to local control of sarcomas of the extremities is resection of the tumor with adequate margins. The role of adjuvant treatment, particularly following LSS, is still being evaluated. The risk factor profile should be considered when selecting a treatment program for patients with lower extremity sarcomas.

Adolescent↗

Upper extremity bypass grafting. A 15-year experience.

OBJECTIVE: To analyze the perioperative morbidity and mortality, long-term patient survival, and patency characteristics of arterial bypass related to upper extremity ischemia. DESIGN: This is a retrospective review of sequential patients undergoing upper extremity arterial bypass during a 15-year period at a single tertiary-care teaching hospital. Data are expressed in a 5-year life-table format and interpreted using log-rank analysis. PATIENTS: Seventy-four patients with upper extremity ischemia undergoing arterial bypass, which included 95 separate operations. MAIN OUTCOME MEASURES: Operative morbidity and mortality, life-table survival, life-table bypass graft patency, and limb salvage are reported. RESULTS: There was no operative mortality, and there was a single major amputation. Survival rate was 86% at 5 years, and overall patency rate was 61.2% at 5 years, with autogenous conduits superior at all sites compared with prosthesis (70.9% vs 37.7%). Secondary operation was inferior to primary bypass (66% vs 48%) and associated with higher morbidity (22% vs 5%). All far distal forearm prosthetic bypass grafts failed within 1 year. CONCLUSIONS: Primary upper extremity bypass with venous conduit is a safe, durable procedure, after which prolonged patient survival can be expected.

Adolescent↗

Magnetic resonance angiography for the evaluation of lower extremity arterial disease: a meta-analysis.

CONTEXT: Magnetic resonance angiography (MRA) is a rapidly evolving technique that has been reported to be accurate for assessment of lower extremity arterial disease. OBJECTIVE: To obtain the best available estimates of the diagnostic performance of MRA in patients with lower extremity arterial disease. DATA SOURCES: Studies published from January 1985 through May 2000 in English, German, or French, identified from the MEDLINE, EMBASE, and Current Contents databases. STUDY SELECTION: Studies were included that allowed construction of 2 x 2 contingency tables for detection of stenosis greater than 50% or occlusion with MRA or arteriography in patients with claudication or critical ischemia. DATA EXTRACTION: Two observers graded the following elements of study quality: consecutively enrolled patients, prospective study design, clear cut-off levels, blinded assessment, and clear description of MRA technique. Summary receiver operating characteristic analysis was performed to examine the influence of year of publication, all methodological criteria, arterial tract, number of subdivisions within arterial tracts, and MRA technique on diagnostic performance. DATA SYNTHESIS: Of 3583 studies initially identified, 34 were included that evaluated MRA in 1090 patients (72% men; median age, 65 years). Magnetic resonance angiography was highly accurate for assessment of all lower extremity arteries. Three-dimensional gadolinium-enhanced (3-D Gd) MRA improved diagnostic performance compared with 2-D MRA (relative diagnostic odds ratio, 2.8 [95% confidence interval, 1.2-6.4]), adjusted for number of subdivisions within arterial tracts. The estimated points of equal sensitivity and specificity were 94% and 90% for 3-D Gd MRA and 2-D MRA, respectively. CONCLUSIONS: Magnetic resonance angiography is highly accurate for assessment of the entire lower extremity for arterial disease. Three-dimensional Gd-enhanced MRA improves diagnostic performance compared with 2-D MRA.

Aged↗

Pharmacokinetics of dacarbazine in the regional perfusion of extremities with melanoma.

BACKGROUND: The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required. METHODS: A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC. 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). 99(m)Tc (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity. RESULTS: High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity. CONCLUSIONS: High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion.

Antineoplastic Agents↗

Extremity soft tissue sarcoma with metastases to abdominopelvic surfaces.

BACKGROUND: In a majority of patients with extremity soft tissue sarcoma, the lungs are the first site at which recurrent disease is detected. Other common sites of recurrence are the resection site, bone metastasis, and liver metastasis. Although abdomino pelvic sarcomatosis is common as a site of recurrence for visceral and retroperitoneal sarcoma, it has not been previously reported for extremity sarcoma. METHOD: We present three patients in whom extremity soft tissue sarcoma metastasized to the peritoneal surfaces, and in all three patients this was symptomatically the dominant site for recurrence. All of them underwent a palliative surgical cytoreduction and were then treated with intraperitoneal chemotherapy. RESULTS: In two of the three patients, isolated progression of peritoneal sarcomatosis has again occurred: one patient remains disease free at 14 months. CONCLUSIONS: Metastasis to peritoneal surfaces within the abdomen and pelvis must be considered a possible site for systemic dissemination of extremity soft tissue sarcomas. Effective treatments for sarcoma spread to peritoneal surfaces would benefit this small but symptomatic group of patients.

Adult↗

Anatomic and physiologic evaluation of upper extremity ischemia.

This study assessed the accuracy of arteriography and laser Doppler perfusion imaging (LDPI) as predictors of digital ischemia and correlated upper extremity symptoms, function, and nutritional flow with arteriographic and laser Doppler assessments. Multiple-level occlusive disease was documented in 25 hands (23 patients) by arteriography. LDPI demonstrated one or more hypoperfused digits in 17 hands. Patient questionnaires were used to assess upper extremity symptoms, pain, cold sensitivity, and function. Spearman correlation coefficients indicated that arteriography is a poor indicator of nutritional perfusion as measured by LDPI. Neither arteriography or laser Doppler perfusion imaging served as an indicator of the severity of cold intolerance. However, upper extremity symptoms and functional status correlated with both laser Doppler measurements and the level of cold sensitivity. Laser Doppler perfusion imaging and arteriographic analysis provide complimentary data in the evaluation of upper extremity ischemia.

Adolescent↗

Upper extremity replantation: three-year experience.

Microsurgery in Mexico was initiated in 1967, when the first report of the subspecialty was published. At our hospital, we have had a well-organized microsurgery department since 1995. This has improved our management of patients with amputations of the upper extremity. This article presents our experience with upper extremity replantation, including hand and fingers. During the first 3 years, we managed 55 patients, 42 male and 13 female, aged 2-52 years, who had suffered amputations of some part of their upper extremity or even of the complete limb. These patients underwent surgical exploration for replantation. We analyzed 103 amputations in the 55 patients operated. The amputated parts are summarized as follows: 11 thumbs, 25 index, 24 middle, 22 ring, and 12 little fingers; 5 hands, 5 forearms, and 2 arms. The average hospital stay was 10 days. The follow-up was 6-24 months. Replantation success was 82%, with 18% failure for survival of the replanted part. Functional recovery was satisfactory in the 50% of cases, and sensitive recovery was satisfactory in 75% of cases. We conclude that although our experience on upper extremity replantation is not so large, our results are similar to those from other series. We discussed our results.

Adolescent↗

Epinephrine for the resuscitation of apparently stillborn or extremely bradycardic newborn infants.

BACKGROUND: Epinephrine is a cardiac stimulant with complex effects on the heart and blood vessels. It has been used for decades in all age groups to treat cardiac arrest and bradycardia. Despite formal guidelines for the use of epinephrine in neonatal resuscitation, the evidence for these recommendations has not yet been rigorously scrutinised. While it is understood that this evidence is in large part derived from animal models and the adult human population, the contribution from work in the neonatal population remains unclear. In particular, it remains to be determined if any randomised studies in neonates have helped to establish if the administration of epinephrine in the context of apparent stillbirth or extreme bradycardia might influence mortality and morbidity. OBJECTIVES PRIMARY OBJECTIVE: ~bullet~To determine if the administration of epinephrine to apparently stillborn and extremely bradycardic newborns reduces mortality and morbidity Secondary objectives: ~bullet~To determine the effect of intravenous versus endotracheal administration on mortality and morbidity ~bullet~To determine the effect of high dose versus standard dose epinephrine on mortality and morbidity, where high dose is defined as any dose greater than the current recommended standard dose of 0.1 to 0.3ml/kg of a 1:10,000 solution of epinephrine ~bullet~To determine whether the effect of epinephrine on mortality and morbidity varies with gestational age, i.e. term (greater than or equal to 37 weeks) versus pre-term (less than 37 weeks) SEARCH STRATEGY: Searches were made of Medline from 1966 to December 2002, CINAHL (from 1982), Current Contents (from 1988), EMBASE, and the Cochrane Controlled Trials Register (2002, issue 4). Bibliographies of conference proceedings were reviewed and unpublished studies were sought by hand searching the conference proceedings of the Society for Pediatric Research and the European Society for Pediatric Research from 1993 to 2002. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of newborns, both pre-term and term, receiving epinephrine for unexpected apparent stillbirth or extreme bradycardia. DATA COLLECTION AND ANALYSIS: No studies were found meeting the criteria for inclusion in this review MAIN RESULTS: No studies were found meeting the criteria for inclusion in this review. REVIEWER'S CONCLUSIONS: We found no randomised, controlled trials evaluating the administration of epinephrine to the apparently stillborn or extremely bradycardic newborn infant. Similarly, we found no randomised, controlled trials which addressed the issues of optimum dosage and route of administration of epinephrine. Current recommendations for the use of epinephrine in newborn infants are based only on evidence derived from animal models and the human adult literature. Randomised trials in neonates are urgently required to determine the role of epinephrine in this population.

Bradycardia↗

In search of spatial extremes.

In environmental studies attention increasingly focuses on identification of spatial extremes: locations with observations that are apparently higher than either a preset background threshold or neighbouring observations. We consider various procedures for identifying values and locations of these extremes: extreme value theory, conditionally simulated fields and disjunctive kriging. In a recent research project we studied the distribution of nine environmental pollutants (heavy metals, polyaromatic hydrocarbons and mineral oil) in a large industrial estate in the southern Netherlands. This area is interesting as it is influenced by three contaminating processes: inundation by the river Meuse, anthropogenic heightening with contaminated materials and local industrial activities. Concentrations are measured. In this paper the peaks over threshold method was useful for finding extremes for spatially uncorrelated variables, whereas conditional simulations applied in particular to areas with spatial dependence.

Animals↗

Assessment of upper extremity role functioning in students.

BACKGROUND: Upper extremity symptoms associated with use of computers and other upper extremity activities are common in students. Research on these disorders requires psychometrically sound measures of health-related student role function; no such measure is available currently. METHODS: Based upon input from students and clinicians, we developed a 10-item scale to measure student health-related role function. The measure was administered as part of a survey of 193 undergraduates at one university. A follow-up survey was administered 1 month later. The student health-related role function questionnaire was assessed for internal consistency, ceiling effects, convergent and discriminant validity, and responsiveness to self-reported change in functional status. RESULTS: Eighty-two percent of students who were given the survey completed it and 65% completed a follow-up survey 1 month later. The new measure was reliable (Cronbach's alpha 0.87). Forty-six percent of respondents reported "no difficulty" on all items of the health-related student role function measure while 64% reported "no difficulty" on all items of a generic upper extremity functional status measure. This finding indicates that the new measure was better able to detect functional limitations; it had a less prominent ceiling effect. The new measure had moderately high correlations with measures of symptom severity and pain, documenting convergent validity. It distinguished students who utilized clinician services, medications, or academic accommodation from students who did not utilize these resources, documenting discriminant validity. The measure was responsive to self-perceived change, as demonstrated by a highly significant association (P < 0.0001) between changes in score over a 1-month follow-up and students' perceptions of whether they had improved in functional abilities after the month, deteriorated or remained stable. CONCLUSIONS: The student health-related role functioning measure is reliable, valid and responsive to change. It is an appropriate measure for research on upper extremity symptoms in students.

Arm↗

A quantitative assessment of limited joint mobility in patients with diabetes. Goniometric analysis of upper extremity passive range of motion.

OBJECTIVE: The syndrome of limited joint mobility is a common but not widely recognized musculoskeletal complication of diabetes. The purpose of this study was to further characterize this syndrome using quantitative goniometric measures. METHODS: Cross-sectional analysis of a sample population was performed to establish the prevalence, location, and severity of limited joint mobility and to determine its relationship to extraarticular manifestations and complications of diabetes. Passive range of motion of both upper extremities was measured by goniometry in 70 adult patients with insulin-dependent diabetes mellitus and 70 nondiabetic controls who were group-matched for age, sex, and general activity level. Joint mobility was assessed by both individual joint motions and a composite scoring technique. RESULTS: Analysis of individual joints and composite scores revealed significant differences between dominant and nondominant extremities in both the control and the diabetic groups. Diabetic patients were generally less flexible than nondiabetic subjects throughout the arm, especially in shoulder and finger joints. In the full study population, multivariate analysis revealed that advanced age, male sex, and the presence of diabetes were associated with decreased passive range of motion for a majority of joints (P < 0.05). In the diabetes group, passive range of motion was significantly correlated (P < 0.05) with age, sex, duration of diabetes, and to a variable extent, glucose control, but was not correlated with the presence of clinically significant neuropathy, retinopathy, nephropathy, or peripheral vascular disease, with activity level, or with hand dominance. Stepwise regression analysis failed to identify single key joint motion(s) to serve as possible screening tests in predicting generalized limited joint mobility of the upper extremity. Finally, the effect of limb usage on range of motion in flexion may differ in diabetic and nondiabetic subjects. CONCLUSION: Limited joint mobility is a generalized phenomenon occurring throughout the upper extremities of many diabetic patients. It is significantly related to age, sex, and to a variable extent duration of diabetes and glucose control. It is not related to the standard complications of diabetes as defined in this study.

Adult↗

Bone invasion in extremity soft-tissue sarcoma: impact on disease outcomes.

BACKGROUND: The purpose of the current study was to evaluate histologic bone invasion as a predictor of oncologic outcome in extremity soft-tissue sarcoma (STS) patients presenting to a specialty sarcoma center between 1986 and 2001. METHODS: All patients who underwent surgery for extremity STS were identified from the prospective database at the study institution. Patient demographic features were compared using chi-square analyses or independent-sample Student t-tests. The disease outcomes were compared for those with and without bone invasion using Kaplan-Meier survival analysis and Cox modeling. RESULTS: In a review of 874 patients with STS of the extremity, 48 patients (5.5%) had evidence of bone invasion. Patients with bone invasion presented with larger tumors that were more frequently deep in the extremity and more often had metastases at presentation. Patients with bone invasion had lower metastasis-free survival but bone invasion was not found to be an independent prognostic factor (P = .274) on Cox modeling. Bone invasion was found to be prognostic of overall survival on multivariate analysis (P < .0001). CONCLUSIONS: In a small percentage of patients with STS, bone resection may be required to obtain an adequate surgical margin, thereby limiting the risk of local tumor recurrence. Histologic bone invasion portends a poorer prognosis in terms of overall survival.

Adult↗

Use of extreme weight control behaviors with and without binge eating in a community sample: implications for the classification of bulimic-type eating disorders.

OBJECTIVE AND METHOD: To inform the classification of bulimic-type eating disorders not meeting formal diagnostic criteria for bulimia nervosa (BN), levels of eating disorder psychopathology and functional impairment associated with subjective and objective bulimic episodes (SBEs and OBEs) and purging and nonpurging methods of weight control were examined in a large community-based sample of women (n = 5,232). RESULTS: Participants who reported recurrent bulimic episodes had significantly higher levels of eating disorder psychopathology and functional impairment than those who did not and this was the case whether the episodes were objective or subjective. Similarly, participants who reported the use of extreme weight control behaviors had higher levels of eating disorder psychopathology and functional impairment than those who did not, and this was the case whether purging or nonpurging behaviors were employed. The combination of bulimic episodes and extreme weight control behaviors was associated with particularly high levels of eating disorder psychopathology and functional impairment. CONCLUSION: The combination of bulimic episodes, objective or subjective, and extreme weight control behaviors, purging or nonpurging, is significant in terms of impairment in psychosocial functioning among individuals affected by eating disorders not meeting formal diagnostic criteria for BN. The combination of SBEs and extreme weight control behaviors, in particular, warrants further investigation.

Adolescent↗

Diagnosis of arterial occlusive disease of the upper extremities: comparison of color duplex sonography and angiography.

PURPOSE: The aim of this study was to assess the abilities of color duplex sonography (CDUS) to detect and characterize arterial occlusive disease of the upper extremities. METHODS: We prospectively compared the results of CDUS with those of intra-arterial digital subtraction angiography, which were considered definitive, in patients with symptomatic arterial occlusive disease of the upper extremities. In each extremity, we visualized 9 arterial segments, which were each evaluated for stenoses and occlusions. Each segment was categorized on each imaging modality as not significantly narrowed (narrowed by <50%), significantly narrowed (narrowed by > or =50% but <100%), or occluded (100%). RESULTS: We examined a total of 578 segments in 57 patients (34 men and 23 women) with a mean age of 50 years (range, 20-74 years). CDUS had a sensitivity, a specificity, a positive predictive value, a negative predictive value, and an accuracy of 98%, 99%, 97%, 99.5%, and 99%, respectively, for detecting occluded lesions and 79%, 100%, 100%, 99%, and 99%, respectively, for detecting hemodynamically significantly stenotic lesions. Notably, the sensitivity of CDUS for diagnosing significantly stenotic lesions (79%) was lower than that for diagnosing occlusive disease (98%). CONCLUSIONS: With high sensitivity and accuracy rates, CDUS is a reliable screening method for detecting arterial occlusive disease of the upper extremities. This modality efficiently provides anatomic and hemodynamic data that are useful in cases of such disease.

Adult↗

The thoracodorsal artery perforator flap with a vascularized scapular segment for reconstruction of a composite lower extremity defect.

High-energy trauma resulting in a composite defect of the lower extremity confronts the microvascular surgeon with more difficulties than do free flap reconstruction elsewhere in the body, since the choice of distant recipient vessels is particularly difficult. Combining principles of perforator flap surgery with those of composite tissue transfer, we designed a thoracodorsal artery perforator flap with a vascularized bone segment from the scapula for reconstruction of a composite lower extremity defect in a patient following a paragliding accident. This is the first report on the application of a composite thoracodorsal artery perforator flap with vascularized scapula in lower extremity reconstruction. Among its multiple advantages, such as preservation of latissimus dorsi function, it is a good tool for one-stage reconstruction of traumatic composite lower extremity defects because its low donor site morbidity and long vascular pedicle enables anastomosis placement outside the zone of injury.

Humans↗

Correction for regression dilution bias using replicates from subjects with extreme first measurements.

The least squares estimator of the slope in a simple linear regression model will be biased towards zero when the predictor is measured with random error, i.e. intra-individual variation or technical measurement error. A correction factor can be estimated from a reliability study where one replicate is available on a subset of subjects from the main study. Previous work in this field has assumed that the reliability study constitutes a random subsample from the main study. We propose that a more efficient design is to collect replicates for subjects with extreme values on their first measurement. A variance formula for this estimator of the correction factor is presented. The variance for the corrected estimated regression coefficient for the extreme selection technique is also derived and compared with random subsampling. Results show that variances for corrected regression coefficients can be markedly reduced with extreme selection. The variance gain can be estimated from the main study data. The results are illustrated using Monte Carlo simulations and an application on the relation between insulin sensitivity and fasting insulin using data from the population-based ULSAM study. In conclusion, an investigator faced with the planning of a reliability study may wish to consider an extreme selection design in order to improve precision at a given number of subjects or alternatively decrease the number of subjects at a given precision.

Aged↗

Life in unusual environments: progress in understanding the structure and function of enzymes from extreme halophilic bacteria.

Extreme halophilic archaea are saturated with salt and the intracellular electrolyte concentration exceeds that of the extracellular environment. Enzymes and other proteins from extreme halophilic archaea have been purified for many years and studied by biochemical and biophysical solution methodologies. They are active and stable at multimolar salt concentrations and denature below 2 to 3 M NaCl or KCl. Adaptation to these high concentrations of salt, genetic and evolutionary aspects, and the possibility of biotechnological applications are problems of considerable interest. Since the status of this fascinating field of research was reviewed in 1992, malate dehydrogenase from Haloarcula marismortui, now known to be a tetramer, was sequenced, its gene was cloned and expressed in active form, and its physical properties were redefined. A single mutation of Arg100 (in the enzyme active site) to Gln switched the enzyme specificity from malate to lactate dehydrogenase. Recent determination of its molecular structure by X-ray crystallography (O. Dym et al., in press) provides an exciting basis for the understanding of the structure and function of extreme halophilic enzymes. A major problem which so far has not been tackled in the study of extreme halophilic archaea is the understanding of protein nucleic acid interactions which are essential for the performance of biological function. Whereas the stability and activity of enzymes and other proteins can be modified to perform at high salt concentrations by use of currently known structural concepts, the existence of meaningful protein nucleic acid interactions in physiological concentrations of 4 to 5 M KCl constitutes an unsolved enigma worth intensive investigation.

Environment↗