RESUMEN

Mounting evidence from models and geological data implies that the Antarctic Ice Sheet may behave in an unstable manner and retreat rapidly in response to a warming climate, which is a key factor motivating efforts to improve estimates of Antarctic ice volume contributions to future sea-level rise. Here, we review Antarctic cooling history since peak temperatures of the Middle Eocene Climatic Optimum (approx. 50 Ma) to provide a framework for future initiatives to recover sediment cores from subglacial lakes and sedimentary basins in Antarctica's continental interior. While the existing inventory of cores has yielded important insights into the biotic and climatic evolution of Antarctica, strata have numerous and often lengthy time breaks, providing a framework of 'snapshots' through time. Further cores, and more work on existing cores, are needed to reconcile Antarctic records with the more continuous 'far-field' records documenting the evolution of global ice volume and deep-sea temperature. To achieve this, we argue for an integrated portfolio of drilling and coring missions that encompasses existing methodologies using ship- and sea-ice-/ice-shelf-based drilling platforms as well as recently developed seafloor-based drilling and subglacial access systems. We conclude by reviewing key technological issues that will need to be overcome.

RESUMEN

Plant protection problems are simulated by a system of ordinary differential equations with given initial conditions. The sensitivity and resistance of pathogen subpopulations to fungicide mixtures, fungicide weathering, plant growth, etc. are taken into consideration. The system of equations is solved numerically for each set of initial conditions and parameters of the disease and fungicide applications. Optimization algorithms were investigated and a computer program was developed for optimization of these solutions. 14 typical cases of the disease were simulated and optimized in order to determine optimal fungicide treatments. The optimized strategy for fungicide application differs considerably from the commonly used method and seems to be an important new principle in plant protection. The approach developed in this study may be useful for a wide spectrum of purposes in the simulation of leaf diseases. It may also help the biologist to decrease or pinpoint experimental work and analyze its results and is perspective for plant disease control.

Asunto(s)

RESUMEN

1. Intracerebroventricular (i.c.v.) administration of ouabain to rats induces motor hyper- and hypoactivity that have been hypothesized to model the mania and depression of bipolar illness, respectively. 2. The extent of ouabain-induced change in activity may vary according to the test environment. 3. To determine the degree of differential response to i.c.v. ouabain in the open field and automated activity monitors, the authors examined a large number of animals (n=40) in both environments. 4. I.c.v. ouabain produced a four-fold increase in open field activity versus i.c.v. artificial cerebrospinal fluid (aCSF) (mean +/- SD: 258.7 +/- 316.61 vs. 84.8 +/- 86.16 squares traversed) (t = 2.648, P = 0.011), but did not alter horizontal activity in automated activity monitors (8193.5 +/- 4902.52 vs. 7088.47 +/- 3046.85 beam interruptions) (t = 0.847, P = 0.4). This increase in activity persisted for at least one week (161.0 +/- 186.35 for i.c.v. ouabain vs. 46.1 +/- 47.46 for i.c.v. aCSF, P = 0.065). 5. Open field is superior to automated activity monitors in capturing ouabain-induced hyperlocomotion response.

Asunto(s)

RESUMEN

BACKGROUND: The ability to measure productivity, work performed, or contributions toward the clinical mission has become an important issue facing anesthesiology departments in private practice and academic settings. Unfortunately, the practice and billing of anesthesia services makes it difficult to quantify individual productivity. This study examines the following methods of measuring individual productivity: normalized clinical days per year (nCD/yr); time units per operating-room day worked (TU/OR day); normalized time units per year (nTU/yr); total American Society of Anesthesiologists (ASA) units per OR day (tASA/OR day); and normalized total ASA units per year (ntASA/yr). METHODS: Billing and scheduling data for clinical activities of faculty members of an anesthesiology department at a university medical center were collected and analyzed for the 1998 fiscal year. All clinical sites and all clinical faculty anesthesiologists were included unless they spent less than 20% of their time during the fiscal year providing clinical care, i.e., less than 0.2 clinical full-time equivalent. Outliers, defined as faculty who had productivity greater or less than 1 SD from the mean, were examined in detail. RESULTS: Mean and median values were reported for each measurement, and different groups of outliers were identified. nCD/yr identified faculty who worked more than their clinical full-time equivalent would have predicted. TU/OR day and tASA/OR day identified apparently low-productivity faculty as those who worked a large portion of their time in obstetric anesthesia or an ambulatory surgicenter. tASA/OR day identified specialty anesthesiologists as apparently high-productivity faculty. nTU/yr and ntASA/yr were products of the per-OR day measurement and nCD/yr. CONCLUSION: Each of the measurements studied values certain types of productivity more than others. By defining what type of service is most important to reward, the most appropriate measure or combination of measures of productivity can be chosen. In the authors' department, nCD/yr is the most useful measure of individual productivity because it measures an individual anesthesiologist's contribution to daily staffing, includes all clinical sites, is independent of nonanesthesia factors, and is easy to collect and determine.

Asunto(s)

RESUMEN

Intracerebroventricular (i.c.v.) administration of ouabain has been shown to alter motor activity in the rat. It has been purported that this may model the behavioral abnormalities of human manic-depressive (bipolar) illness. Since manic-depression is a recurrent condition, we elected to investigate the effects of the multiple administration of i.c.v. ouabain. Male Sprague-Dawley rats were allowed to acclimate to the animal facility for 7-10 days after which time i.c.v. cannulae were placed. Animals received two i.c.v. injections of either ouabain (10[-3] M) or artificial cerebrospinal fluid (aCSF) 9 days apart, so that 6 rats received aCSF-aCSF, 6 received ouabain-aCSF, and 6 received ouabain-ouabain. Behavioral activity was evaluated in an open field (86 x 86 cm subdivided into sixteen 21.5 x 21.5-cm squares) for 20 min at baseline and immediately following each i.c.v. injection. After the last behavioral test, the animals were killed, and the brains were rapidly harvested and dissected over ice. Specific ouabain binding and sodium pump activity were determined. A single dose of ouabain produced a marked increase (297.0%, p = 0.002) in open field activity compared to both baseline behavior and to aCSF injected animals. The effects of ouabain appeared to last for 9 days. A second i.c.v. injection of either ouabain (136.5 +/- 60.4 SEM) or aCSF (108.0%, p < 0.01) had no effect on the activity level which was intermediate between the initial ouabain hyperactivity and the baseline level. Nine days after ouabain administration, hippocampal ouabain binding was increased relative to the control group (5477 +/- 485.7 vs. 3579 +/- 518.6, p < 0.05) and sodium pump activity was relatively lower (2293.8 +/- 265.5 vs. 3174.2 +/- 410.5, p < 0.05).

Asunto(s)

RESUMEN

A total of 1,717 total hip and 2,769 total knee medical device reports submitted to the U.S. Food and Drug Administration (FDA) from 1984 through 1993 were reviewed. A large percentage of total hip complications could be attributed to some aspect of component modularity. Cementless modular acetabular components were the single largest source of device-related complications. Fifty-six percent of total knee medical device reports (MDRs) were associated with accelerated polyethylene wear. By location, MDRs identified patellar (46%), tibial (33%), and femoral (5%) component complications. It was estimated that less than 5% of device-related complications were reported to the FDA. Based on the reports received, it was apparent that mechanical failure of components was a common and increasing cause of total joint revision.

Asunto(s)

RESUMEN

Both mania and bipolar depression have been associated with decrements in the activity of the sodium and potassium-activated adenosine triphosphatase (Na,K-ATPase) membrane pump. Although the role of this observation in the pathophysiology of bipolar illness is unclear, it has been proposed that this defect could be central to the pathogenesis of the illness. In an effort to test this hypothesis, the authors examined the efficacy of lithium pretreatment in attenuating behavioral changes secondary to acute administration of a single intracerebroventricular (i.c.v.) dose of the Na,K-ATPase-inhibiting compound, ouabain, in the Sprague-Dawley rat. Ouabain (10(-3)M) significantly decreased motor activity in automated activity monitors. Lithium pretreatment for 7 d totally prevented this effect. These preliminary data suggest that i.c.v. ouabain administration in the rat may prove to be a viable animal model for bipolar illness.

Asunto(s)

RESUMEN

Twenty consecutive cases of infected total knee replacements surgically treated between 1990 and 1993 in which complete clinical and financial data were available were reviewed to determine the resources required of the hospital and the surgeon. These results were compared with a similar analysis of a stratified, unselected sample 30 cases each of primary total knee arthroplasty and nonseptic revision total knee arthroplasty during the same period. Parameters compared between the infected total knee replacement, noninfected revision total knee replacement, and primary total knee replacement included number of surgical procedures performed, number of hospitalizations, number of hospital days, total operative time, and total intraoperative blood loss. Financial data included the amount charged and reimbursed by the hospital and by the surgeon. The actual hospital cost was estimated as well. Based on all parameters measured, surgical treatment of the infected total knee implant required 3 to 4 times the resources of the hospital and the surgeon compared with a primary total knee implant and approximately twice the resources of a nonseptic revision total knee implant. The reimbursement received resulted in an estimated net loss of approximately $15,000 per case to the hospital for the group as a whole, but approximately $30,000 per case per Medicare patient.

Asunto(s)

RESUMEN

Alcohol has been shown to confound the initial assessment of trauma victims, and cocaine is associated with numerous medical and anesthetic complications. A prospective study was performed to determine the prevalence of alcohol and illicit drug use in orthopedic trauma patients at an inner-city teaching hospital. All patients admitted to the orthopedic service during a 2-year period (January 1993 to December 1994) were prospectively studied. Patients < 14 years old were excluded. Blood alcohol levels were determined, and the urine was screened for cocaine, opiates, marijuana, barbiturates, amphetamines, benzodiazepines, and phencyclidine. Demographic data and a medical history were obtained. Seven hundred sixty-six patients met the study parameters. Of these, 628 (82%) had complete drug and alcohol screens available for review. The data were then sorted by diagnosis, mechanism of injury, type of injury (closed versus open), length of inpatient stay, age, sex, and race, and a statistical analysis was performed. The overall incidence of positive drug or alcohol tests was 56%. Twenty-four percent of patients tested positive for two or more drugs, and 9% for three or more. Alcohol (25%) was the most commonly detected drug, followed by cocaine (22%) and marijuana (21%). The highest incidence of drug use was found in males and in those ages 31-40 years. Hospital stay averaged 1.3 days longer in patients with positive screens. Patients with tibia fractures or open fractures, and those injuries sustained by gunshot, altercation, or pedestrian versus motor vehicle accident had the highest incidence of positive screens. These data show that drug-using patients have more severe orthopedic injuries (i.e., open fractures) and require longer hospitalizations. We conclude that drug and alcohol use is widespread in patients presenting with orthopedic injuries and we make recommendations regarding treatment of these patients. The majority of orthopedic trauma resources in this setting is devoted to treating intoxicated patients. Drug and alcohol use is a major social problem and may have an adverse effect on patient care.

Asunto(s)

RESUMEN

1. In human bipolar patients mania and bipolar depression are both characterized by decreased membrane Na,K-AtPase activity. Additionally, digoxin neurotoxicity in patients frequently presents with symptoms of mania or depression. 2. These findings suggest that central nervous system Na,K-ATPase inhibition may play a pathophysiologic role in bipolar illness. 3. The authors tested this hypothesis by administering intracerebroventricular (i.c.v.) ouabain to rats at sublethal doses. The authors then measured behavioral activity as total square crossings in an open field. 4. Motoric activity was significantly increased by i.c.v. administration of 5 microliters of ouabain at 10(-3) M. This preliminary study suggests that i.c.v. ouabain administration may provide a useful animal model of mania that is based on observed biochemical changes in humans.

Asunto(s)

RESUMEN

Cathepsin A (EC 3.4.16.1), a lysosomal carboxypeptidase, has been purified 1374-fold from pig kidney. Purification steps included concanavalin A-Sepharose and phenyl-Sepharose chromatography and chromatofocusing. The specific activity (16.9 U/mg) of the purified enzyme was significantly higher than previously reported values. The enzyme preparation appeared homogeneous when analyzed by non-denaturing polyacrylamide gel electrophoresis and was free of detectable protease contamination. The molecular mass (M(r) = 97,000), isoelectric point (5.0), and sensitivity to inhibitors were consistent with reported properties of cathepsin A. However, the previously reported three-peptide chain structure was not observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence or absence of 2-mercaptoethanol demonstrated that the enzyme is composed of two M(r) 47,000 subunits, each of which dissociate in the presence of 2-mercaptoethanol into two polypeptide chains of 19,000 and 31,000.

Asunto(s)

RESUMEN

Angiotensin carboxypeptidase (ACP) activity has been detected in urine samples from normal subjects and patients with hypertension and diabetes by determining the enzyme's ability to convert angiotensin I to des-Leu angiotensin I. Gel filtration chromatography of a concentrated urine sample indicated that about equal amounts of the enzyme exist as 100 kDa and 500 kDa molecular weight forms, respectively. This ACP activity co-eluted with activity that cleaved histidine from des-Leu angiotensin I to form angiotensin II and activity that cleaved tyrosine from benzyloxycarbonyl-glutamyl-tyrosine (ZGT). These results suggest that the urinary ACP activity is due to cathepsin A as we have reported previously for the porcine kidney enzyme. Analysis of sequential urine samples from a single individual over a 6-day period revealed as much as a 6-fold fluctuation in creatinine-normalized ACP activity. Of five male healthy adult subjects, the creatinine-normalized urinary ACP activity ranged from 1.7 to 3.7 mU/mL with a mean of 2.8 mU/mL. However, five male patients with renovascular hypertension had elevated levels of ACP activity with a mean of 11.6 mU/mL. Of five male patients with diabetic nephropathy, all had elevated ACP activity levels with a mean of 21.0 mU/mL. It is concluded that ACP activity in the urine is due to cathepsin A probably derived from kidney tissue, and that the release is increased in patients with kidney damage. We suggest that urinary ACP activity should be evaluated further for a possible relationship to renal hypertension and as a potentially early marker for diabetic nephropathy.

Asunto(s)

RESUMEN

The development of a structured psychoeducational support group model for blood donors who tested positive for human immunodeficiency virus Type I antibody is described. Salient group therapy techniques and educational content are discussed, issues of group structure are identified, and the need for support of clinicians is highlighted.

Asunto(s)

Asunto(s)

RESUMEN

We have reported the existence of a carboxypeptidase in a human renal extract that converts Angiotensin I (AI) to Angiotensin II (AII) in two steps with des-leu-AI (dl-AI) being formed as an intermediate. Since this carboxypeptidase had properties similar to cathepsin A, the ability of cathepsin A to metabolize AI was studied. Cathepsin A was purified from hog kidney with enzyme activity being monitored using both benzyloxycarbonyl-glutamyl-tyrosine (ZGT) and AI as substrates. The procedure separated the expected large and small molecular weight forms of cathepsin A as well as two additional isoenzymes. All of the isoenzymes had carboxypeptidase activity with ZGT, AI, and dl-AI. No detectable cleavage of AII was observed. Cathepsin A,S (small) activity with ZGT or AI as substrate was inhibited to a similar extent by diisopropylfluorophosphate, mersalyl acid, and a decapeptide renin inhibitor. It is concluded that the renal angiotensin carboxypeptidase activity is catalyzed by cathepsin A. By its ability to convert AI to AII, cathepsin A may be a component of the intrarenal renin-angiotensin system.

Asunto(s)

RESUMEN

The crude rat and bovine synaptosomal lysate from brain can hydrolyze angiotensin I (AI) to des-Leu angiotensin I (AI-dL) and no further. This cytosolic enzyme has a specificity for angiotensin-related sequences, R-His-Pro-Phe-His-Leu and therefore named angiotensin-related carboxypeptidase (ARC). These studies led to the biosynthesis and purification of AI-dL in order to determine if it can provoke a drinking response. This nonapeptide is a potent dipsogen when injected into the cerebroventricles of rats. The drinking response probably requires a second hydrolysis to angiotensin II (AII) since both captopril and saralasin can inhibit this response.

Asunto(s)

RESUMEN

Whole brain synaptosomes contain both an isorenin activity and angiotensin-related carboxypeptidase activity. Further hydrolysis of des-Leu angiotensin I (AI-dL) occurs more slowly; hydrolysis of angiotensin II (AII) is negligible. Vasopressin and oxytocin but not vasotocin can inhibit angiotensin-related carboxypeptidase activity. Since AII has been shown to induce vasopressin secretion, this correlation suggests a feedback inhibition by vasopressin of this enzymatic cascade. Commercially available radioimmunoassays for AI and AII show a 3.4 and 6.0% crossreactivity, respectively. When the absolute concentration of AI-dL exceeded 500 ng/ml, both antibodies to AI and AII showed maximal displacement of radiolabel. This suggests that these antibodies may not distinguish between AI-dL from other peptides during immunocytochemistry.

Asunto(s)

RESUMEN

Angiotensin II, the potent hypertensive octapeptide, can be generated by a sequential cleavage of the carboxyl-terminal leucine and histidine from angiotensin I by a human renal extract. This extract does not hydrolyze further the resulting octapeptide. The more widely recognized biosynthetic pathway is by the extracellular dipeptide cleavage of angiotensin I by an enzyme which also degrades bradykinin, i.e., angiotensin converting enzyme. The presence of a carboxypeptidase activity capable of generating but not further hydrolyzing angiotensin II was observed in an ammonium sulfate fraction of a human renal extract. This novel enzymatic activity is distinct from angiotensin converting enzyme activity in that it is not dependent upon calcium and is not inhibited by known angiotensin converting enzyme inhibitors.

Asunto(s)

RESUMEN

A simple, rapid method is described for the purification of radioiodinated peptides for use in radioimmuno- and in radioreceptor assays. Iodinated reaction mixtures are applied directly onto Sep-Pak disposable, reversed phase cartridges equilibrated with phosphate buffer. Unreacted 125-iodide and other non-peptide reaction components are eluted with buffer. The peptide fraction is then eluted with 70% buffer: 30% acetonitrile. The peptide fraction is further purified by reversed phase high pressure liquid chromatography to separate the native peptide and the mono- and diiodo-derivatives. In this study the method is used to prepare 125-iodide-labeled monoiodo-leucine enkephalin and monoiodo-angiotensin II, which are free of the parent peptides and diiodo-derivatives and are of maximum obtainable specific radioactivity. The usefulness of these labeled peptides in radioimmuno- and radioreceptor assays is demonstrated by their binding to specific antibodies and receptors, respectively.

Asunto(s)

Asunto(s)