Rupture of a hepatic artery aneurysm and renal infarction: 2 complications of fibromuscular dysplasia that mimic vasculitis

Fibromuscular dysplasia (FMD) is one of the most important mimics of vasculitis. FMD is more prevalent in women and may cause infarcts of organ systems including the brain, intestines, and extremities. These acute clinical presentations often raise the suspicion of vasculitis and therefore rheumatologists will be asked to evaluate these patients. One of the frequent manifestations of FMD is renal artery involvement. Angiographic evaluation often shows a "string of beads" appearance of the renal arteries but sometimes only tapering of the vascular lumen or cutoffs may be seen. In contrast, hepatic artery involvement with FMD occurs much less frequently and may initially present with life threatening intraabdominal bleeding. Celiac angiograms of these patients often show aneurysms, a presentation similar to vasculitis. Only a high level of suspicion for FMD and careful evaluation of clinical facts will lead to correct diagnosis. This will prevent the wrong diagnosis of vasculitis and subsequent treatment with potentially toxic medications. We present 2 cases of FMD involving the renal and hepatic arteries that illustrate this diagnostic challenge.     

Multiple evolutionary origins of the fungus causing Panama disease of banana: concordant evidence from nuclear and mitochondrial gene genealogies

Panama disease of banana, caused by the fungus Fusarium oxysporum f. sp. cubense, is a serious constraint both to the commercial production of banana and cultivation for subsistence agriculture. Previous work has indicated that F. oxysporum f. sp. cubense consists of several clonal lineages that may be genetically distant. In this study we tested whether lineages of the Panama disease pathogen have a monophyletic origin by comparing DNA sequences of nuclear and mitochondrial genes. DNA sequences were obtained for translation elongation factor 1alpha and the mitochondrial small subunit ribosomal RNA genes for F. oxysporum strains from banana, pathogenic strains from other hosts and putatively nonpathogenic isolates of F. oxysporum. Cladograms for the two genes were highly concordant and a partition-homogeneity test indicated the two datasets could be combined. The tree inferred from the combined dataset resolved five lineages corresponding to "F. oxysporum f. sp. cubense" with a large dichotomy between two taxa represented by strains most commonly isolated from bananas with Panama disease. The results also demonstrate that the latter two taxa have significantly different chromosome numbers. F. oxysporum isolates collected as nonpathogenic or pathogenic to other hosts that have very similar or identical elongation factor 1alpha and mitochondrial small subunit genotypes as banana pathogens were shown to cause little or no disease on banana. Taken together, these results indicate Panama disease of banana is caused by fungi with independent evolutionary origins.     

Cancer pain management in developing countries: a mosaic of complex issues resulting in inadequate analgesia

OBJECTIVE: To determine the prevalence of suicidal ideation and the symptomatic profile as well as to identify the sociodemographic characteristics highlighting female adolescents with the highest scores on suicidal ideation in adolescents living in Mexico City: students and suicidal patients. MATERIAL AND METHODS: A cross-sectional and ex-post-facto study was carried out in order to analyze information from two samples: 1,712 junior and junior high school women students (representative student sample in Mexico City), and 30 adolescents inpatient hospitalized for her suicide attempts (clinical sample). RESULTS: Prevalence of presence as well as persistence of suicidal ideation were higher in the clinical sample, nevertheless 11.8% of the school sample had everyone of the symptoms in a range of 1 to 7 days. The most persistent of the ideation symptoms was: "My family would be better if I were dead"; and in the clinical sample it was "I thought about killing myself". Finally, the sociodemographic characteristics that best matched the student girls having the highest scores in suicidal ideation were: to be on junior high school, to get low grades, to acknowledge school performance as bad and to have interrupted her studies. The characteristics that highlight the girls with a first attempt were analyzed in the clinic sample in comparison with those ones with two or more attempts. It was significant that girls in the second group were living only with one parent and they thought in the last attempt that their dead would be possible or certain. CONCLUSIONS: The prevalence of suicidal ideation was important in the school sample. If it is considered that this psychological construct has a strong association with suicidal attempt, and multiple suicide conduct, then is a priority to detect adolescents in risk and to make preventive efforts, considering the sociodemographic characteristics that configurate in risk for suicidal ideation.     

Assessment of the nutritional state of dialysis patients

Obstructive sleep apnea syndrome (OSAS) has been associated with a higher than normal cardiovascular morbidity and mortality. Some OSAS patients lack the sleep-related, nocturnal decrease, or "dip," in blood pressure which is seen in normal individuals. These subjects, called "non-dippers," may be at greater risk for cardiovascular problems. We studied 40 OSAS patients (including 3 women) and 6 control subjects, all identified by polysomnography, for nocturnal blood pressure "dipping." We performed a second nocturnal polysomnogram to determine their apnea and hypopnea indices, (A + H)I, and oxygen saturation levels at the beginning of the study and then initiated 48 hours of ambulatory blood pressure monitoring, with data points collected every 30 minutes. Controls, which included one hypertensive subject, were all dippers. Nineteen OSAS subjects (48% of OSAS individuals) were systolic non-dippers and only 9 of them (22.5%) were diastolic non-dippers. We considered the following clinical variables as potential predictors of non-dipping: age, body mass index, respiratory disturbance index, years of reported loud snoring by bed partners, lowest oxygen saturation during nocturnal sleep, and percentage of sleep time spent with oxygen saturation below 90%. Multiple regression analyses indicated respiratory disturbance index as the only significant variable for systolic (p = 0.04) and diastolic (p = 0.03) blood pressure non-dipping. When we forced the following two nonsignificant variables into the model, they showed a very meager impact: number of years with reported loud snoring (p = 0.4 and p = 0.5, respectively for systolic and diastolic blood pressure non-dipping) and age (p = 0.5 and p = 0.6). The calculated model explained only a low percentage of the variance with an r2 of 0.25 and 0.26 for systolic and diastolic blood pressure non-dipping, respectively. Analysis of hypertension/normotension and dipping/non-dipping failed to show a significant relationship in the studied population. Fifty percent of the normotensive OSAS subjects were non-dippers and 43% of the hypertensive OSAS subjects were also non-dippers. We found a relationship between increasing respiratory disturbance index and increasing average 24-hour systolic blood pressure only when OSAS subjects were non-dippers and hypertensive.     

Iterative optimization of high-affinity proteases inhibitors using phage display. 1. Plasmin

We generated a series of libraries having variants of the first Kunitz domain of human lipoprotein-associated coagulation inhibitor (LACI-D1, also known as tissue-factor pathway inhibitor-I) displayed on bacteriophage M13 as pIII-fusions. We varied LACI-DI iteratively in two regions: the P1 region (positions 10-21) and the "second loop", (positions 31-39), which together form one end of the domain. Display-phage library Lib#1 allows 31 200 amino-acid sequences in P1 region (residues 13, 16-19). Preliminary, we screened Lib#1 against human plasmin (PLA, EC 3.4.21.7) immobolized on agarose to enrich for phage displaying variants with PLA affinity. We introduced a 1600-fold increase in second-loop diversity (residues 31, 32, 34, 39) into the population of selectants from Lib#1, yielding Lib#2. Lib#2 (allowing approximately 50 million amino-acid sequences) was screened against PLA-agarose to isolate highest affinity binders. Protein EPI-P211, derived from the best isolate of Lib#2, inhibits PLA with Ki = 2 nM (at least 500-fold better than LACI-D1) and with high specificity. We used amino-acid sequences of PLA-binding selectants to design a PLA-biased library (Lib#3) which we screened against PLA. The protein EPI-P302 (derived from the best binder obtained from Lib#3) has Ki for PLA inhibition of 87 pM, which is 25-fold better than the first-round best binder and > or = 12 500-fold better than LACI-D1. EPI-P302 also shows very high specificity for PLA vs other human proteases and is resistant to inactivation by oxidants and extremes of temperature or pH. Thus, one can use selectants from one library to design target-tailored combinatorial libraries and obtain quite stable, highly specific, very high-affinity binding molecules while maintaining an essentially human framework.     

The course of geriatric depression with "reversible dementia": a controlled study

OBJECTIVE: The goals of this longitudinal investigation were 1) to study the rate of development of irreversible dementia in elderly depressed patients with a dementia syndrome that subsided after improvement of depression and 2) to compare it with that of depressed, never-demented patients. METHOD: The subjects were 57 elderly patients consecutively hospitalized for major depression. At entry into the study, 23 subjects also met criteria for "reversible dementia," while 34 were without dementia. After a systematic clinical evaluation, the subjects were followed up at approximately yearly intervals for an average of 33.8 months. RESULTS: Irreversible dementia developed significantly more frequently in the depressed group with reversible dementia (43%) than in the group with depression alone (12%). Survival analysis showed that the group with reversible dementia had a 4.69-times higher chance of having developed dementia at follow-up than the patients with depression alone. No clinical characteristics at entry into the study were found to discriminate the subjects who developed irreversible dementia during the follow-up period from those who remained nondemented. CONCLUSIONS: These findings suggest that geriatric depression with reversible dementia is a clinical entity that includes a group of patients with early-stage dementing disorders. Therefore, identification of a reversible dementia syndrome is an indication for a thorough diagnostic workup and frequent follow-ups in order to identify treatable neurological disorders.     

Comparative analysis of 8-oxo-2' -deoxyguanosine in DNA by 32P- and 33P-postlabeling and electrochemical detection

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is emerging as a useful marker for oxidative DNA damage. Reported basal levels determined by 32P-postlabeling (PPL) method were 10-fold or more higher than those obtained with HPLC/electrochemical detection (ECD). This discrepancy was investigated. In commercial calf thymus DNA, levels of 4 +/- 1 and 64 +/- 14 8-oxo-dG per 10(6) 2'-deoxynucleosides (dN) were measured by the standard HPLC/ECD and PPL methods, respectively. DNA digestion by micrococcal nuclease/spleen phosphodiesterase and nuclease P1 (as used in the standard PPL method), followed by ECD analysis resulted in a level of 8 +/- 3. In calf thymus DNA spiked with chemically synthesized 8-oxo-dGp to give an increment of 9 8-oxo-dG/10(6) dN, the added standard produced a significant increase with HPLC/ECD but not PPL. After spiking the DNA with 90 8-oxo-dG/10(6) dN, the added 8-oxo-dGp was detectable also with PPL, with a labeling efficiency of 65%. In order to investigate the role of ionizing radiation from 32P for the higher 8-oxo-dG levels in PPL, incubation times and amounts of radioactivity in the phosphorylation reaction with commercial dGp were increased, and external irradiation of commercial dG with 32P was investigated. All modifications resulted in higher values of 8-oxo-dG measured, but the effect was not large enough to fully explain the discrepancy between PPL and HPLC/ECD. Using [gamma-33P]ATP instead of [gamma-32P]ATP or adding [33P]phosphate to a 32P-PPL assay resulted in even higher levels of 8-oxo-dG measured. The increase in 8-oxo-dG levels during the PPL workup is attributed to the presence and oxidation of unmodified dGp in the reaction mixture. For a determination of true basal levels, the PPL method will have to be modified, including the removal of dGp prior to the phosphorylation reaction.     

Characterization of the radical trapping activity of a novel series of cyclic nitrone spin traps

alpha-Phenyl-tert-butyl nitrone (PBN) is a nitrone spin trap, which has shown efficacy in animal models of oxidative stress, including stroke, aging, sepsis, and myocardial ischemia/reperfusion injury. We have prepared a series of novel cyclic variants of PBN and evaluated them for radical trapping activity in vitro. Specifically, their ability to inhibit iron-induced lipid peroxidation in liposomes was assessed, as well as superoxide anion (O2(-.)) and hydroxyl radical ((.)OH) trapping activity as determined biochemically and using electron spin resonance (ESR) spectroscopy. All cyclic nitrones tested were much more potent as inhibitors of lipid peroxidation than was PBN. The unsubstituted cyclic variant MDL 101,002 was approximately 8-fold more potent than PBN. An analysis of the analogs of MDL 101,002 revealed a direct correlation of activity with lipophilicity. However, lipophilicity does not solely account for the difference between MDL 101,002 and PBN, inasmuch as the calculated octanol/water partition coefficient for MDL 101,002 is 1.01 as compared to 1.23 for PBN. This indicated the cyclic nitrones are inherently more effective radical traps than PBN in a membrane system. The most active compound was a dichloro analog in the seven-membered ring series (MDL 104,342), which had an IC50 of 26 mum, which was 550-fold better than that of PBN. The cyclic nitrones were shown to trap (.)OH with MDL 101,002 being 20 25 times more active than PBN as assessed using 2-deoxyribose and p-nitrosodimethylaniline as substrates, respectively. Trapping of (.)OH by MDL 101,002 was also examined by using ESR spectroscopy. When Fenton's reagent was used, the (.)OH adduct of MDL 101,002 yielded a six-line spectrum with hyperfine coupling constants distinct from that of PBN. Importantly, the half-life of the adduct was nearly 5 min, while that of PBN is less than 1 min at physiologic pH. MDL 101,002 also trapped the O2(-.) radical to yield a six-line spectrum with coupling constants very distinct from that of the (.)OH adduct. In mice, the cyclic nitrones ameliorated the damaging effects of oxidative stress induced by ferrous iron injection into brain tissue. Similar protection was not afforded by the lipid peroxidation inhibitor U74006F, thus implicating radical trapping as a unique feature in the prevention of cell injury. Together, the in vivo activity, the stability of the nitroxide adducts, and the ability to distinguish between trapping of (.)OH and O2(-.) suggest the cyclic nitrones to be ideal reagents for the study of oxidative cell injury.     

A prospective randomized comparison of epidural infusion of fentanyl and intravenous administration of morphine by patient-controlled analgesia after radical retropubic prostatectomy

In a prospective, randomized study, continuous infusion of epidural fentanyl citrate (group E) was compared with patient-controlled intravenously administered morphine sulfate (group P) for analgesia in 66 men after radical retropubic prostatectomy. Although both methods provided satisfactory analgesia, the mean comfort level scores were lower (that is, greater comfort) in group E than in group P at all observation times. The difference in mean resting comfort level scores between groups E and P was statistically significant (P < or = 0.05) at 9 of the 11 observation times. In addition, significant differences in comfort level scores were noted at 8 of the 11 observation times during deep breathing, 5 of 11 during coughing, and 3 of 9 during ambulation. Maximal and minimal comfort level scores recorded by each patient during the course of the study were significantly lower (that is, less pain) in group E than in group P for all four categories of activity. The percentage of patients who reported no pain was significantly higher in group E than in group P at 9 of 11 observation times during resting and 5 of 11 observation times during deep breathing. No significant differences were noted in side effect profiles or duration of hospital stay. In summary, when two effective methods of analgesia used after radical retropubic prostatectomy were compared prospectively, patients who received epidural infusion of fentanyl were more comfortable than those with patient-controlled intravenous administration of morphine, as evidenced by lower mean, maximal, and minimal comfort level scores and a greater proportion of patients with complete relief of pain.