Changes in circulating inflammatory markers following febrile non-haemolytic transfusion reactions to leucoreduced red cells.

It would be desirable to be able to distinguish fever as a result of febrile non-haemolytic transfusion reactions (FNHTR) from other febrile conditions. To further characterize the inflammatory feature of FNHTR, we measured a large panel of inflammatory markers in pre- and posttransfusion plasma samples from patients with and without FNHTR following the transfusion of leucoreduced red blood cells. As FNHTR patients only displayed a significant increase in IL-6, we conclude that changes in plasma cytokine levels during FNHTR are unlikely to be used diagnostically. An incidental finding of a distinct cytokine pattern in pretransfusion samples from FNHTR patients warrants further investigations, as it might be used to characterize the nature of FNHTR and to predict the risk of these adverse events.

Steroid hormone regulation of nuclear proto-oncogenes.

The role of the nuclear proto-oncogenes as rapidly responding nuclear regulators in the cascade model for steroid hormone action is proposed. In this model, the nuclear proto-oncogenes respond within minutes to steroids and would code for regulatory proteins that in turn enter the nucleus to positively or negatively regulate "late" structural gene transcription and mRNA processing. The potential involvement of the nuclear matrix and one of its components, a receptor binding factor (RBF-1) for steroid receptors of these genes, is discussed. The nuclear proto-oncogenes, thus, may serve as important "early" regulatory genes and as excellent universal markers in all tissues in steroid hormone action. Proto-oncogenes are known to be regulatory genes since genetic alterations of amplification, mutations, chromosome translocation, and other rearrangements which result in overexpression, inactivation, and/or loss of regulatory control result in malignant transformation of the cell. It is now known that as many as six different proto-oncogenes must undergo alteration to induce the loss of cellular control of replication and/or for transformation to occur. The nuclear oncogenes, representing only one class of several of the known proto-oncogenes, code for transcription factors and enzymes involved in regulating these factors and other features of gene transcription. Possibly RNA processing is another function. Many of these genes and their responses to steroids are described in this chapter. The steroid receptors belong to a family which themselves represent transcription factors in that they reside in the nucleus and bind to specific DNA elements or other transcription factors to alter gene transcription and/or mRNA processing. The receptors for the various steroids are described as having a common structural motif and function using the above mentioned pathways. In the majority of cases cited, the steroid receptors mediate the rapid regulation of the nuclear proto-oncogene transcription. The role of palindromic SRE in or near these genes is to bind steroid hormone receptor dimers to regulate transcription. More powerful steroid response units (SRU), composed of two or more response elements for steroids or transcription factors, can act at great distances from the gene as enhancers for steroid- regulated transcription. What has become obvious from the studies of steroid effects on nuclear proto-oncogenes, is that, despite the tremendous scientific strides that have been made toward understanding gene regulation by steroids, we are still relatively naive.(ABSTRACT TRUNCATED AT 400 WORDS)

Body mass index greater than 35 is associated with severe Clostridium difficile infection.

BACKGROUND: Obesity has been implicated in the acquisition of Clostridium difficile infections (CDI), however, no study has investigated whether there is a correlation between body mass index (BMI) and CDI severity. AIM: To determine whether obesity, as measured by BMI correlates with severe hospital-onset or community-onset CDI. METHODS: Patients admitted with CDI at a tertiary-care center from January 2013 to June 2015 were identified. The cohort was stratified by onset of disease using the National Healthcare Safety Network criteria, and by severity using the 2013 American College of Gastroenterology guidelines. Multivariate logistic regression was used to determine independent predictors of severe CDI. RESULTS: A total of 196 met the inclusion criteria, of which 57.1% (112) met criteria for severe disease. Overall, BMI >35 kg/m2 was 1.7-fold more likely to be associated with severe CDI compared to a BMI 20-35 kg/m2 (P < 0.005), and was an independent predictor of severe CDI (P = 0.038). In patients with community-onset-CDI and hospital-onset-CDI, a BMI >35 kg/m2 was associated with a 1.96-fold and 1.48 greater rate of severe CDI compared to a BMI 20-35 kg/m2 (P = 0.004 and 0.048), and was an independent predictor of severe CDI in these cohorts (P = 0.039 and 0.027) respectively. CONCLUSION: This study has identified an association between body mass index and Clostridium difficile infection severity. A BMI>35 kg/m2 is an independent risk factor for severe community-onset and hospital-onset Clostridium difficile infections.

Nuclear matrix acceptor binding sites for steroid hormone receptors: a candidate nuclear matrix acceptor protein.

Steroid/nuclear-hormone receptors are ligand-activated transcription factors that have been localized to the nuclear matrix. The classic model of hormone action suggests that, following activation, these receptors bind to specific "steroid response elements" on the DNA, then interact with other factors in the transcription initiation complex. However, evidence demonstrates the existence of specific chromatin proteins that act as accessory factors by facilitating the binding of the steroid receptors to the DNA. One such protein, the "receptor binding factor (RBF)-1", has been purified and shown to confer specific, high-affinity binding of the progesterone receptor to the DNA. Interestingly, the RBF-1 is localized to the nuclear matrix. Further, the RBF-1 binds specifically to a sequence of the c-myc proto-oncogene that has the appearance of a nuclear matrix attached region (MAR). These results, and other findings reviewed here, suggest that the nuclear matrix is involved intimately in steroid hormone-regulated gene expression.

Incidence, outcomes, and cost of foot ulcers in patients with diabetes.

OBJECTIVE: To determine the incidence of foot ulcers in a large cohort of patients with diabetes, the risk of developing serious complications after diagnosis, and the attributable cost of care compared with that in patients without foot ulcers. RESEARCH DESIGN AND METHODS: Retrospective cohort study of patients with diabetes in a large staff-model health maintenance organization from 1993 to 1995. Patients with diabetes were identified by algorithm using administrative, laboratory, and pharmacy records. The data were used to calculate incidence of foot ulcers, risk of osteomyelitis, amputation, and death after diagnosis of foot ulcer, and attributable costs in foot ulcer patients compared with patients without foot ulcers. RESULTS: Among 8,905 patients identified with type 1 or type 2 diabetes, 514 developed a foot ulcer over 3 years of observation (cumulative incidence 5.8%). On or after the time of diagnosis, 77 (15%) patients developed osteomyelitis and 80 (15.6%) required amputation. Survival at 3 years was 72% for the foot ulcer patients versus 87% for a group of age- and sex-matched diabetic patients without foot ulcers (P < 0.001). The attributable cost for a 40- to 65-year-old male with a new foot ulcer was $27,987 for the 2 years after diagnosis. CONCLUSIONS: The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes.

Chronic care clinics for diabetes in primary care: a system-wide randomized trial.

OBJECTIVE: To evaluate the impact of primary care group visits (chronic care clinics) on the process and outcome of care for diabetic patients. RESEARCH DESIGN AND METHODS: We evaluated the intervention in primary care practices randomized to intervention and control groups in a large-staff model health maintenance organization (HMO). Patients included diabetic patients > or = 30 years of age in each participating primary care practice, selected at random from an automated diabetes registry. Primary care practices were randomized within clinics to either a chronic care clinic (intervention) group or a usual care (control) group. The intervention group conducted periodic one-half day chronic care clinics for groups of approximately 8 diabetic patients in their respective doctor's practice. Chronic care clinics consisted of standardized assessments; visits with the primary care physician, nurse, and clinical pharmacist; and a group education/peer support meeting. We collected self-report questionnaires from patients and data from administrative systems. The questionnaires were mailed, and telephoned interviews were conducted for nonrespondents, at baseline and at 12 and 24 months; we queried the process of care received, the satisfaction with care, and the health status of each patient. Serum cholesterol and HbA1c levels and health care use and cost data was collected from HMO administrative systems. RESULTS: In an intention-to-treat analysis at 24 months, the intervention group had received significantly more recommended preventive procedures and helpful patient education. Of five primary health status indicators examined, two (SF-36 general health and bed disability days) were significantly better in the intervention group. Compared with control patients, intervention patients had slightly more primary care visits, but significantly fewer specialty and emergency room visits. Among intervention participants, we found consistently positive associations between the number of chronic care clinics attended and a number of outcomes, including patient satisfaction and HbA1c levels. CONCLUSIONS: Periodic primary care sessions organized to meet the complex needs of diabetic patients imrproved the process of diabetes care and were associated with better outcomes.

The use of automated data to identify complications and comorbidities of diabetes: a validation study.

We evaluated the accuracy of administrative data for identifying complications and comorbidities of diabetes using International Classification of Diseases, 9th edition, Clinical Modification and Current Procedural Terminology codes. The records of 471 randomly selected diabetic patients were reviewed for complications from January 1, 1993 to December 31, 1995; chart data served to validate automated data. The complications with the highest sensitivity determined by a diagnosis in the medical records identified within +/-60 days of the database date were myocardial infarction (95.2%); amputation (94.4%); ischemic heart disease (90.3%); stroke (91.2%); osteomyelitis (79.2%); and retinal detachment, vitreous hemorrhage, and vitrectomy (73.5%). With the exception of amputation (82.9%), positive predictive value was low when based on a diagnosis identified within +/-60 days of the database date but increased with relaxation of the time constraints to include confirmation of the condition at any time during 1993-1995: ulcers (88.5%); amputation (85.4%); and retinal detachment, vitreous hemorrhage and vitrectomy (79.8%). Automated data are useful for ascertaining potential cases of some diabetic complications but require confirmatory evidence when they are to be used for research purposes.

Chronic care clinics: a randomized controlled trial of a new model of primary care for frail older adults.

OBJECTIVE: To determine whether a new model of primary care, Chronic Care Clinics, can improve outcomes of common geriatric syndromes (urinary incontinence, falls, depressive symptoms, high risk medications, functional impairment) in frail older adults. DESIGN: Randomized controlled trial with 24 months of follow-up. Physician practices were randomized either to the Chronic Care Clinics intervention or to usual care. SETTING: Nine primary care physician practices that comprise an ambulatory clinic in a large staff-model HMO in western Washington State. PARTICIPANTS: Those patients aged 65 and older in each practice with the highest risk for being hospitalized or experiencing functional decline. INTERVENTION: Intervention practices (5 physicians, 96 patients) held half-day Chronic Care Clinics every 3 to 4 months. These clinics included an extended visit with the physician and nurse dedicated to planning chronic disease management; a pharmacist visit that emphasized reduction of polypharmacy and high-risk medications; and a patient self-management/support group. Control practices (4 physicians, 73 patients) received usual care. MEASUREMENTS: Changes in self-reported urinary incontinence, frequency of falls, depressive symptoms, physical function, and satisfaction were analyzed using an intention-to-treat analysis adjusted for baseline differences, covariates, and practice-level variation. Prescriptions for high-risk medications and cost/utilization data obtained from administrative data were similarly analyzed. RESULTS: After 24 months, no significant improvements in frequency of incontinence, proportion with falls, depression scores, physical function scores, or prescriptions for high risk medications were demonstrated. Costs of medical care including frequency of hospitalization, hospital days, emergency and ambulatory visits, and total costs of care were not significantly different between intervention and control groups. A higher proportion of intervention patients rated the overall quality of their medical care as excellent compared with control patients (40.0% vs 25.3%, P = .10). CONCLUSIONS: Although intervention patients expressed high levels of satisfaction with Chronic Care Clinics, improved outcomes for selected geriatric syndromes were not demonstrated. These findings suggest the need for developing greater system-wide support for managing geriatric syndromes in primary care and illustrate the challenges of conducting practice improvement research in a rapidly changing delivery system.

Malignant melanoma metastatic to a meningioma.

The case presented is that of a 63 year old man with a metastasis to an intracranial meningioma from a malignant melanoma. Although the phenomenon of tumor to tumor metastasis to a meningioma has been previously reported, this is the first case in the literature to date, in which the primary tumor is a malignant melanoma. The criteria for the diagnosis of tumor-to-tumor metastasis and possible reasons for the frequency of metastasis to meningiomas are briefly reviewed.

Patient-level estimates of the cost of complications in diabetes in a managed-care population.

OBJECTIVE: To develop incidence-based estimates of the cost of several diabetes-related complications. DESIGN AND SETTING: This was a retrospective cohort study in a large health maintenance organisation. A total of 8905 patients with type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus and 36,520 age- and gender-matched controls without diabetes were observed from 1992 to 1995. Incidence rates of 6 major diabetes-related complications were computed for both populations. Annual health expenditures in the first and second year following diagnosis were computed for each complication. For comparison, annual costs were derived for individuals without diabetes or the complication of interest. MAIN OUTCOME MEASURES AND RESULTS: Over 3 years of observation, incidence rates for the groups with and without diabetes were as follows: myocardial infarction 9.0 versus 3.2%; stroke 8.7 versus 3.8%; hypertension 26.2 versus 16.9%; end-stage renal disease 5.9 versus 1.4%; foot ulcer 7.9 versus 1.1%; and eye disease 44.3 versus 2.8%. Expressed as a multiple of the average annual cost of care for those without diabetes [$US3400/year (1995 dollars) for those over 65 years of age] and the related complication of interest, excess expenditures for those with diabetes were as follows for the first year following diagnosis: no complications 1.59; myocardial infarction 4.1; stroke 3.5; hypertension 2.56; end-stage renal disease 4.32; foot ulcer 4.0; and eye disease 2.46. For younger cohorts (less prevalent in the sample), incremental costs for each complication were generally greater than in the older group. CONCLUSIONS: The high incidences and costs may support the value of aggressive early intervention for patients with diabetes. These data will be useful for pharmacoeconomic modelling of the cost effectiveness of new and existing therapies for this condition.

Influence of PGRs on carbohydrate content in Lipaphis erysimi (Kalt.).

Six compounds (IBA, chlorogenic acid, cytokinine, GA3, alar B-9 and maleic hydrazide) belonging to four different categories of plant growth hormones were used to study their effect on carbohydrate content in L. erysimi. The second instar nymphs (48 hr old) were given both dipping and leaf surface treatment with 1024 ppm concentration of compounds for two time intervals i.e. 48 and 96 hr. The carbohydrate content decreased after treatment with 4 of the plant growth regulators i.e. GA3, alar B-9, IBA and chlorogenic acid with maximum suppression in GA3 treatment. Cytokinine did not induce any derogatory influence on carbohydrate content. The treatment with maleic hydrazide, on the other hand enhanced the carbohydrate content. It could be concluded that the application of these PGRs affected the carbohydrate synthesis or metabolism.

Interaction of the chaperone calreticulin with proteins and peptides of different structural classes.

The interaction of calreticulin with native and denatured forms and polypeptides in proteolytic digests of proteins representing structural classes of all-alpha-helix (hemoglobin, serum albumin), all-beta-sheet (IgG) and alpha-helix + beta-sheets (lysozyme, ovalbumin) was investigated. The binding of calreticulin to denatured proteins was found to depend on conformation and structural class of the protein. No interaction was observed with the native proteins, whereas binding was seen for the denatured proteins, the order of interaction being lysozyme = IgG > ovalbumin >> hemoglobin = serum albumin. Moreover, the interaction between calreticulin and the heat-denatured proteins depended on the temperature and time used for denaturation and the degree of proteolytic fragmentation. Calreticulin bound well to peptides in proteolytic digests from protease K or chymotrypsin treatment of lysozyme, IgG and ovalbumin but weakly or not at all to peptides in proteolytic digests of hemoglobin and serum albumin. Synthetic peptides from lysozyme and ovalbumin confirmed binding to hydrophobic peptides from these proteins. These results show that calreticulin has the ability to interact with denatured and fragmented forms of proteins with a preference for beta-strand structure and hydrophobicity.

Deep venous thrombosis revealed during ultrasound-guided femoral nerve block.

Ultrasound imaging used to facilitate performance of a femoral nerve block also affords imaging of adjacent anatomical structures. Following a fracture of the femur, an ultrasound guided femoral nerve block (UGFNB) was performed to provide analgesia; this led to the incidental finding of a previously undiagnosed femoral vein thrombosis (DVT), resulting in a change in patient management before surgery. An inferior vena cava (IVC) filter was placed before intramedullary nailing of the fracture.

Ultrasound-guided infraclavicular brachial plexus block.

BACKGROUND: Peripheral nerve blocks are almost always performed as blind procedures. The purpose of this study was to test the feasibility of seeing individual nerves of the brachial plexus and directing the block needle to these nerves with real time imaging. METHODS: Using ultrasound guidance, infraclavicular brachial plexus block was performed in 126 patients. Important aspects of this standardized technique included (i) imaging the axillary artery and the three cords of the brachial plexus posterior to the pectoralis minor muscle, (ii) marking the position of the ultrasound probe before introducing a Tuohy needle, (iii) maintaining the image of the entire length of the needle at all times during its advancement, (iv) depositing local anaesthetic around each of the three cords and (v) placing a catheter anterior to the posterior cord when indicated. RESULTS: In 114 (90.4%) patients, an excellent block permitted surgery without a need for any supplemental anaesthetic or conversion to general anaesthesia. In nine (7.2%) patients local or perineural administration of local anaesthetic, and in three (2.4%) conversion to general anaesthesia, was required. Mean times to administer the block, onset of block and complete block were 10.0 (SD 4.4), 3.0 (1.3) and 6.7 (3.2) min, respectively. Mean lidocaine dose was 695 (107) mg. In one patient, vascular puncture occurred. In 53 (42.6%) patients, an indwelling catheter was placed, but only three required repeat injections, which successfully prolonged the block. CONCLUSION: The use of ultrasound appears to permit accurate deposition of the local anaesthetic perineurally, and has the potential to improve the success and decrease the complications of infraclavicular brachial plexus block.

Spontaneous angiographic disappearance of an intracranial arteriovenous malformation.

A deep right hemisphere AVM was demonstrated by angiography in an 8-year-old girl soon after her presentation with a subarachnoid haemorrhage. Eight years later the AVM was no longer visible on angiography. During the interval she had been completely asymptomatic and had received no treatment. There was no residual neurological deficit or epilepsy. A similar case has previously been described and is discussed briefly along with other cases of complete AVM regression.

Mid-arm approach to basilic and cephalic vein cannulation using ultrasound guidance.

Central venous lines are often used when there is difficulty obtaining peripheral venous access. The basilic and cephalic veins in the mid-arm region, although difficult to see or palpate, can be imaged longitudinally and cannulated using real-time ultrasonography, providing an easy alternative. These techniques are described, with reports of four typical cases.