A unique case of acute embolus in a renal transplant with salvage by catheter-directed thrombolysis.

INTRODUCTION: Acute renal transplant emboli can be disastrous and result in loss of the renal transplant. This case was successfully treated with thrombolysis. CASE PRESENTATION: A 66-year-old female underwent a right-sided deceased heart-beating donor renal transplant. She had excellent transplant function but presented acutely three years later with pain in the transplanted kidney, an acute rise in serum creatinine and new onset atrial fibrillation. Bedside ultrasound scan demonstrated absent transplant perfusion. Emergency angiogram confirmed acute emboli in the transplant renal artery with some kidney perfusion. Thrombolysis with alteplase and anticoagulation with heparin was commenced. Serial imaging at 24 and 36 h demonstrated significant improvement in transplant perfusion. Following a period of supportive therapy, her transplant function recovered, although not to pre-morbid baseline levels. CONCLUSION: Consider acute embolus in a renal transplant patient with acute kidney injury, transplant tenderness and cardiac arrhythmia. Early thrombolysis may salvage renal transplants and good transplant function may be regained.

Race, Medical Mistrust, and Segregation in Primary Care as Usual Source of Care: Findings from the Exploring Health Disparities in Integrated Communities Study.

Compared to White Americans, African-Americans are less likely to use primary care (PC) as their usual source of care. This is generally attributed to race differences in socioeconomic status and in access to primary care services. Little is known about the relationship between race differences in medical mistrust and the usual source of care disparity. Using data from the Exploring Health Disparities in Integrated Communities (EHDIC) study, we examined the role of medical mistrust in choosing usual source of care in 1408 black and white adults who were exposed to the same healthcare facilities and low-income racially integrated community. Multinomial logistic regression models were estimated to examine the relationship between race, medical mistrust, and usual source of care. After adjusting for demographic and health-related factors, African-Americans were more likely than whites to use the emergency department (ED) (relative risk ratio [RRR] = 1.43 (95 % confidence interval (CI) [1.06-1.94])) and hospital outpatient department (RRR1.50 (95 %CI [1.10-2.05])) versus primary care as a usual source of care. When medical mistrust was added to the model, the gap between African-Americans' and whites' risk of using the ED versus primary care as a usual source of care closed (RRR = 1.29; 95 % CI [0.91-1.83]). However, race differences in the use of the hospital outpatient department remained even after accounting for medical mistrust (RRR = 1.67; 95 % CI [1.16-2.40]). Accounting for medical mistrust eliminated the ED-as-usual-source of care disparity. This study highlights the importance of medical mistrust as an intervention point for decreasing ED use as a usual source of care by low-income, urban African-Americans.

Health insurance and chronic conditions in low-income urban whites.

Little is known about how health insurance contributes to the prevalence of chronic disease in the overlooked population of low-income urban whites. This study uses cross-sectional data on 491 low-income urban non-elderly non-Hispanic whites from the Exploring Health Disparities in Integrated Communities-Southwest Baltimore (EHDIC-SWB) study to examine the relationship between insurance status and chronic conditions (defined as participant report of ever being told by a doctor they had hypertension, diabetes, stroke, heart attack, anxiety or depression, asthma or emphysema, or cancer). In this sample, 45.8 % were uninsured, 28.3 % were publicly insured, and 25.9 % had private insurance. Insured participants had similar odds of having any chronic condition (odds ratios (OR) 1.06; 95 % confidence intervals (CI) 0.70-1.62) compared to uninsured participants. However, those who had public insurance had a higher odds of reporting any chronic condition compared to the privately insured (OR 2.29; 95 % CI 1.21-4.35). In low-income urban areas, the health of whites is not often considered. However, this is a significant population whose reported prevalence of chronic conditions has implications for the Medicaid expansion and the implementation of health insurance exchanges.

Solid-state NMR study of antimicrobial peptides from Australian frogs in phospholipid membranes.

Antimicrobial peptides, isolated from the dorsal glands of Australian tree frogs, possess a wide spectrum of biological activity and some are specific to certain pathogens. These peptides have the capability of disrupting bacterial membranes and lysing lipid bilayers. This study focused on the following amphibian peptides: (1) aurein 1.2, a 13-residue peptide; (2) citropin 1.1, with 16 residues; and (3) maculatin 1.1, with 21 residues. The antibiotic activity and structure of these peptides have been studied and compared and possible mechanisms by which the peptides lyse bacterial membrane cells have been proposed. The peptides adopt amphipathic alpha-helical structures in the presence of lipid micelles and vesicles. Specifically 15N-labelled peptides were studied using solid-state NMR to determine their structure and orientation in model lipid bilayers. The effect of these peptides on phospholipid membranes was determined by 2H and 31P solid-state NMR techniques in order to understand the mechanisms by which they exert their biological effects that lead to the disruption of the bacterial cell membrane. Aurein 1.2 and citropin 1.1 are too short to span the membrane bilayer while the longer maculatin 1.1, which may be flexible due to the central proline, would be able to span the bilayer as a transmembrane alpha-helix. All three peptides had a peripheral interaction with phosphatidylcholine bilayers and appear to be located in the aqueous region of the membrane bilayer. It is proposed that these antimicrobial peptides have a "detergent"-like mechanism of membrane lysis.

The orientation of the antibiotic peptide maculatin 1.1 in DMPG and DMPC lipid bilayers. Support for a pore-forming mechanism.

Maculatin 1.1 is an antimicrobial peptide isolated from the Australian tree frog Litoria genimaculata that adopts an amphipathic, alpha-helical structure in solution. Its orientation and conformation when incorporated to pre-formed DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) and DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) vesicles was determined using polarised Fourier transform infrared-attenuated total reflection infrared and deuterium exchange experiments. For DMPG membranes, our results show insertion of 70% of the maculatin 1.1 molecules, with an angle of insertion of approximately 35 degrees to the membrane normal and with a predominant alpha-helical structure. These results suggest that maculatin 1.1 acts through a pore-forming mechanism to lyse bacterial membranes. A similar degree of insertion in DMPG (65%) and alpha-helical structure was observed for a biologically inactive, less amphipathic maculatin 1.1 analogue, P15A, although the helix tilt was found to be greater (46 degrees) than for maculatin 1.1. Similar experiments performed using DMPC liposomes showed poor insertion, less than 5%, for both maculatin 1.1 and its analogue. In addition, the shape of the amide I band in these samples is consistent with alpha-helix, beta-structure and disordered structures being present in similar proportion. These results clearly show that maculatin 1.1 inserts preferentially in negatively charged membranes (DMPG) which mimic the negatively charged membrane of Gram-positive bacteria. We attribute the high percentage of insertion of the biologically inactive analogue in DMPG to the fact that its concentration on the membrane surface in our experiments is likely to be much higher than that found in physiological conditions.

Negative ion fragmentations of deprotonated peptides: backbone cleavages directed through both Asp and Glu.

The collision-induced spectra of [M - H](-) ions of a variety of natural and synthetic amphibian peptides containing Asp and/or Glu exhibit characteristic gamma backbone cleavage ions that identify the positions of these residues in the peptide. A theoretical study suggests that the Glu cleavage involves an S(N)i reaction of the carboxylate anion from the Glu alpha side chain to form a deprotonated cyclic lactone. The presence of either Asp or Glu or other residues that effect pronounced side-chain cleavages (e.g. Ser or Thr) results in the normal alpha and beta backbone cleavages being reduced in comparison to those cleavages which originate from side chains.

Bioactive dahlein peptides from the skin secretions of the Australian aquatic frog Litoria dahlii: sequence determination by electrospray mass spectrometry.

Eleven dahlein peptides are present in the skin secretion of the Australian aquatic frog Litoria dahlii. All peptides have been sequenced using a combination of electrospray mass spectrometry (ES-MS) and Lys-C digestion/MS, with each sequence confirmed by automated Edman sequencing. The 13-residue dahlein 1 peptides (e.g. dahlein 1.1 GLFDIIKNIVSTL-NH(2)) exhibit weak wide-spectrum antimicrobial activity but no significant activity in the anticancer testing program of the National Cancer Institute (Washington). There are no potent antimicrobial peptides present in the glandular secretion, but the dahleins 5 strongly inhibit the formation of NO by neuronal nitric oxide synthase (e.g. dahlein 5.1 GLLGSIGNAIGAFIANKLKP-OH).

Stabilizing membrane proteins.

Membrane proteins can be extremely stable in a bilayer environment, but are often unstable and rapidly lose activity after detergent solubilization. Poor stability can preclude the detailed characterization of many membrane proteins. One way to alleviate this problem is to find more stable mutants of a membrane protein of interest. This approach is made tractable by the finding that stability-enhancing mutations appear to be relatively common in membrane proteins.

Polymerization of the SAM domain of TEL in leukemogenesis and transcriptional repression.

TEL is a transcriptional repressor that is a frequent target of chromosomal translocations in a large number of hematalogical malignancies. These rearrangements fuse a potent oligomerization module, the SAM domain of TEL, to a variety of tyrosine kinases or transcriptional regulatory proteins. The self-associating property of TEL-SAM is essential for cell transformation in many, if not all of these diseases. Here we show that the TEL-SAM domain forms a helical, head-to-tail polymeric structure held together by strong intermolecular contacts, providing the first clear demonstration that SAM domains can polymerize. Our results also suggest a mechanism by which SAM domains could mediate the spreading of transcriptional repression complexes along the chromosome.

The search for charge-remote reactions of even-electron anions derived from 1,3-disubstituted adamantanes in the gas phase. Retro Diels-Alder and Norrish II processes.

The collision induced decompositions of 3-substituted adamantane carboxylate anions have been studied with a view to uncovering charge-remote fragmentations of the 3-substituent. The 3-substituent is chosen so that it cannot approach the anion site, and so any fragmentations of that substituent should proceed independently of the charged centre, viz. charge-remote reactions. The following systems have been studied (i) the 3-cyclohexenyl system shows no charge-remote retro Diels-Alder fragmentation (DeltaH = +157 kJ mol(-1)), instead, charge-remote loss of the cyclohexenyl radical is noted, (ii) the 3-isobutyl ketone system shows no Norrish II cleavage (loss of C(3)H(6), DeltaH = +18 kJ mol(-1)), instead, the competitive losses of CO(2) from the charged carboxyl centre, together with charge-remote radical loss of the 3-substituent are observed, and (iii) the corresponding 3-isopropyl ester does show the "Norrish II" loss of C(3)H(6), together with competitive losses of CO(2) and the 3-substituent. It is concluded for cases (ii) and (iii), that an adamantane carboxylate anion system with a carbonyl group directly attached at the 3-position is not a suitable model system for studying charge-remote reactions.

Nonstenotic internal carotid arteries: effects of age and blood pressure at the time of scanning on Doppler US velocity measurements.

PURPOSE: To assess the effects of age and blood pressure at the time of scanning on internal carotid artery velocities and cross-sectional diameter at Doppler ultrasonography (US). MATERIALS AND METHODS: During 12 months, 1,020 consecutive patients underwent internal carotid artery Doppler US. No or minimal arterial disease was found in 142 patients (67 women, 75 men). Blood pressure was recorded prior to examination. The angle-corrected internal carotid artery peak systolic and end-diastolic velocities were obtained. The effects of systolic blood pressure, diastolic blood pressure, pulse pressure, age, chronic hypertension, and medications for hypertension on velocities were evaluated by using linear regression analysis. RESULTS: Peak systolic velocity was influenced by age (P =.008), systolic blood pressure (P =.009), diastolic blood pressure (P =.003), and pulse pressure (P =.017) but not history of hypertension (P =.53) or antihypertensive medication use (P =.77). Increasing age decreased peak systolic velocity by 0.34 cm/sec/y. End-diastolic velocity was influenced by age (P <.001) but not by systolic, diastolic, or pulse pressure (all P values were >.13). CONCLUSION: Internal carotid artery peak systolic velocities decrease with advancing age and increase with increasing pulse pressure. The effects of blood pressure at the time of scanning are small, but isolated systolic hypertension could cause increases in spurious velocity.

Inactivation mechanism of the membrane protein diacylglycerol kinase in detergent solution.

We have examined the irreversible inactivation mechanism of the membrane protein diacylglycerol kinase in the detergents n-octyl-beta-D-glucopyranoside (OG) at 55 degrees C and n-decyl-maltopyranoside (DM) at 80 degrees C. Under no inactivation conditions did we find any direct evidence for the chemical modifications that are commonly found in soluble proteins. Moreover, protein inactivated at 55 degrees C in OG could be reactivated by an unfolding and refolding protocol, suggesting that the protein is inactivated by a stable conformational change, not a covalent modification. We also found that the inactivation rate decreased with both increasing protein concentration and increasing thermodynamic stability, consistent with an inactivation pathway involving transient dissociation and/or unfolding of the protein. Our results suggest that the primary cause of diacylglycerol kinase inactivation is not low solubility, but poor intrinsic stability in the detergent environment.

Improving cervical cancer screening in hospital settings.

BACKGROUND: Identifying opportunities to offer cervical cancer screening to underscreened women is important for increasing early detection. Maryland law mandates offering Pap tests during hospital admissions. We examined organizational and physician attitudes and practices regarding inpatient screening, to identify mechanisms for increasing the law's effectiveness. METHODS: We analyzed state admission data, a hospital administrators telephone survey, and a mailed survey of Maryland primary and specialty care physicians, to identify overall patterns and subgroup differences regarding screening. RESULTS: Overall, we found significant concern regarding cancer, and evidence of policies and procedures for screening. However, most hospitals and providers offered screening without assessing clinical need or including persuasive recommendations. Providers with significantly less engagement in preventive assessment and screening included medical and surgical subspecialists and non-primary care providers. Providers to African-American and Medical Assistance women were also less likely to have knowledge, attitudes, and practices conducive to inpatient screening. CONCLUSIONS: Adequate support and infrastructure for preventive screening exist within hospitals. Adding clinical assessment and persuasive education could in crease the impact of these mechanisms, and improve prevention among underscreened inpatient populations.

Attitudes about racism, medical mistrust, and satisfaction with care among African American and white cardiac patients.

The authors examine determinants of satisfaction with medical care among 1,784 (781 African American and 1,003 white) cardiac patients. Patient satisfaction was modeled as a function of predisposing factors (gender, age, medical mistrust, and perception of racism) and enabling factors (medical insurance). African Americans reported less satisfaction with care. Although both black and white patients tended not to endorse the existence of racism in the medical care system, African American patients were more likely to perceive racism. African American patients were significantly more likely to report mistrust. Multivariate analysis found that the perception of racism and mistrust of the medical care system led to less satisfaction with care. When perceived racism and medical mistrust were controlled, race was no longer a significant predictor of satisfaction.

The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis. Part 2. Sequence determination using electrospray mass spectrometry.

Sixteen aurein peptides are present in the host defence secretion from the granular dorsal glands of the Green and Golden Bell Frog Litoria aureus and seventeen from those of the related Southern Bell Frog Litoria raniformis. All peptides have been sequenced using a combination of electrospray mass spectrometry and Lys-C digestion, with each sequence confirmed by automated Edman sequencing. The peptides are named in five groups, viz. aureins 1-5. Ten of these peptides are common to both species of frog. Thirteen of the aurein peptides show wide-spectrum antibiotic and anticancer activity. Amongst the more active peptides are aurein 1.2 (GLFDIIKKIAESF-NH2), the smallest peptide from an anuran reported to have both antibiotic and anticancer activity; aurein 2.2 (GLLDIVKKVIGAFGSL-NH2) and aurein 3.1 (GLFDIVKKIAGHIAGSI-NH2). The aurein 4 and 5 peptides, e.g. aurein 4.1 (GLIQTIKEKLKELAGGLVTGIQS-OH) and aurein 5.1 (GLLDIVTGLLGNLIVDVLKPKTPAS-OH), show neither antibacterial nor anticancer activity.

Value of prone positioning in the ultrasonographic diagnosis of gallstones: prospective study.

To determine prospectively the value of prone/postprone positioning in the sonographic detection of gallstones, 682 patients were scanned in the recumbent, erect, and prone or postprone positions. The gallbladder was evaluated for an intraluminal hyperechoic focus, shadowing, and gravitational dependence and was identified in 679 patients. Among these, 28% had cholelithiasis. In five cases, prone positioning alone revealed gallstones. In 11 of 140 cases, gravitational dependence was only seen with prone scanning. The gallbladder was seen more frequently when the patients were prone than erect. Prone or postprone scanning is a useful supplement to the gallbladder examination, allowing increased demonstration of gravitational dependence and increased stone detection.

The antibiotic and anticancer active aurein peptides from the Australian Bell Frogs Litoria aurea and Litoria raniformis the solution structure of aurein 1.2.

Seventeen aurein peptides are present in the secretion from the granular dorsal glands of the Green and Golden Bell Frog Litoria aurea, and 16 from the corresponding secretion of the related Southern Bell Frog L. raniformis. Ten of these peptides are common to both species. Thirteen of the aurein peptides show wide-spectrum antibiotic and anticancer activity. These peptides are named in three groups (aureins 1-3) according to their sequences. Amongst the more active peptides are aurein 1.2 (GLFDIIKKIAESF-NH2), aurein 2.2 (GLFDIVKKVVGALGSL-NH2) and aurein 3.1 (GLFDIVKKIAGHIAGSI-NH2). Both L. aurea and L. raniformis have endoproteases that deactivate the major membrane-active aurein peptides by removing residues from both the N- and C-termini of the peptides. The most abundant degradation products have two residues missing from the N-terminal end of the peptide. The solution structure of the basic peptide, aurein 1.2, has been determined by NMR spectroscopy to be an amphipathic alpha-helix with well-defined hydrophilic and hydrophobic regions. Certain of the aurein peptides (e.g. aureins 1.2 and 3.1) show anticancer activity in the NCI test regime, with LC50 values in the 10-5-10-4 M range. The aurein 1 peptides have only 13 amino-acid residues: these are the smallest antibiotic and anticancer active peptides yet reported from an anuran. The longer aurein 4 and 5 peptides, e.g. aurein 4.1 (GLIQTIKEKLKELAGGLVTGIQS-OH) and aurein 5. 1 (GLLDIVTGLLGNLIVDVLKPKTPAS-OH) show neither antibacterial nor anticancer activity.

Physician training requirements in sonography: how many cases are needed for competence?

OBJECTIVE: Physician competence in the performance of sonographic studies was assessed after their involvement in predetermined increments of cases to determine whether the case volumes currently required by the American Institute of Ultrasound in Medicine and the American College of Radiology for training in sonography can be lowered substantially. MATERIALS AND METHODS: Sonographic competence tests were administered to 10 first-year diagnostic radiology residents after their involvement in increments of 50 cases, up to a total of 200 cases (four competency tests). Each competency test consisted of the resident's independently scanning and interpreting 10 clinically mandated studies that were scored in comparison with the examination performed by the sonographer and interpreted by an attending radiologist. Trainee studies were graded on the percentage of anatomic landmarks depicted, the number of reporting errors, the number of clinically significant reporting errors, and the percentage of cases receiving a passing score. RESULTS: Although resident performance improved progressively with increasing experience for all parameters assessed, performance of the group was poor even after their involvement in 200 cases. At this testing level, the mean percentage of anatomic landmarks depicted successfully was 56.5%; the mean total reporting errors per case was 1.2; the mean clinically significant errors per case was 0.5; and the mean percentage of cases receiving a passing score was 16%. Impressive performance differences were observed among residents for all parameters assessed, and these differences were not explained by the number of months of radiology training the resident had taken before the sonography rotation. CONCLUSION: Involvement in 200 or fewer cases during the training period is not sufficient for physicians to develop an acceptable level of competence in sonography.

What is the upper limit of normal for the common bile duct on ultrasound: how much do you want it to be?

Conventionally, the upper limit of normal for the common bile duct as measured by ultrasound is considered to be 6 mm. This review is a somewhat personalized account of how that number became the convention and cautions the reader to avoid being slavish in the use of this number. Two specific cautions are not to apply this limit to older patients and to consider where in the common bile duct the measurement was taken, as measurements taken closer to the pancreas may be larger than ones closer to the liver.