The hand eczema proteome: imbalance of epidermal barrier proteins.

BACKGROUND: Chronic hand eczema (CHE) is a common skin disease with a high socioeconomic impact. While some light has been shed on the genetic factors that predispose individuals to the disease, little is known about its actual pathogenesis. OBJECTIVES: We aimed to carry out a systematic and comprehensive analysis of the differential protein expression in CHE using modern mass spectrometry. METHODS: We performed liquid chromatography with tandem mass spectrometry analyses and label-free quantification to analyse the proteomic profile of palmar skin from 12 individuals (six patients with hand eczema and six healthy volunteers). Immunohistochemistry of the palmar skin from seven different patients with hand eczema and seven different healthy volunteers was performed in a second step. RESULTS: With this method we were able to identify 185 candidate proteins with a significantly different abundance in the hand eczema samples. Among them we found several barrier proteins: filaggrin (FLG), FLG-2 and hornerin were all downregulated in the hand eczema samples, as were the desquamation-related enzymes kallikrein-related peptidase (KLK)5 and KLK7 and cystatin E/M. The antimicrobial peptides S100A7 and S100A8/A9 and the small proline-rich protein 2B and S100A11 were upregulated in the diseased skin. Immunohistochemistry confirmed these findings. CONCLUSIONS: Our results corroborate the assumption that skin barrier dysfunction plays an essential role in the pathogenesis of CHE.

[Whirlpool-dermatitis with "hot hands"]. / Whirlpool-Dermatitis mit "hot hands".

HISTORY AND ADMISSION FINDINGS: A 15-year-old boy presented with painful nodules on his palms and discrete pustules on the forearm. Two days earlier he had taken a bath in a new whirlpool. INVESTIGATIONS: Bacteriological examination of the pustules revealed Pseudomonas aeruginosa. The cervical and axillary lymph nodes were inconspicuous. TREATMENT AND COURSE: The dermal infection with Pseudomonas aeruginosa was treated with i.v. piperacillin 4 g/tazobactam 0,5 g twice daily. Furthermore, the patient received 400 mg ibuprofen twice daily per os. Seven days later all symptoms had resolved. CONCLUSION: Hot tubs are a potential source of cutaneous infections with the gram-negative rod Pseudomonas aeruginosa. The most common clinical manifestation of these infections is "hot tub- or jacuzzi-folliculitis" with pustules mainly on the trunk and lymphadenopathy. In children and adolescents, the clinical picture may differ, with a predominance of tender reddish nodules on the palms or soles named "hot hand/hot foot syndrome". In general, the first-line antibiotic in an infection with pseudomonas aeruginosa is ciprofloxacin but it is not recommended in children and adolescents.

[Contact allergy to metals and bone cement components in patients with intolerance of arthroplasty]. / Kontaktallergieraten gegen Metalle und Knochenzementbestandteile bei Patienten mit Endoprothesenunverträglichkeit.

INTRODUCTION: Complications in arthroplasty are mostly attributed to wear particle related loosening, infections or mechanical failure. There is no investigation in a large patient series giving data about the frequency of allergic reactions to metals or bone cement components in arthroplasty with complications. METHODS: In 92 patients with cemented hip or knee arthroplasty (66 patients with complications, 26 without symptoms) patch testing and medical history were evaluated. Contact allergy rates to metals and potential bone cement components were analyzed as well as type of complaints and allergy history. RESULTS: Main complaints were pain (81.8%), reduced range of motion (54.5%) and local swelling (56.1%). Contact allergy to nickel was shown in 16/66 patients (24.2%), 6.1% were allergic to cobalt and 3.0% to chromium. 21/66 patients (31.8%) showed an allergic reaction to bone cement components (gentamicin 23.8%, benzoyl peroxide 10.6%, hydroquinone 4.5%). Sensitization rates in patients without symptoms were 3.8% to nickel as well as to cobalt and chromium, and 15.4% to gentamicin. CONCLUSION: Contact allergy rates to metals and potential bone cement components are higher in arthroplasty patients with complications than in the general population.

Clinical and economic impact of implementing a comprehensive diabetes management program in managed care.

Diabetes mellitus places a significant burden on the U.S. healthcare system. Because of the potential to reduce diabetic complications and costs through intensive management, diabetes has become a primary target for disease management programs. We performed a retrospective analysis of short-term baseline and follow-up clinical, economic, and member and provider satisfaction data from approximately 7,000 people with diabetes being treated through seven managed care plans using Diabetes Treatment Centers of America's Diabetes NetCare, (Nashville, TN), a comprehensive diabetes management program. Our analysis indicates that Diabetes NetCare achieved gross economic adjusted savings of $50 per diabetic member per month (12.3%), with gross unadjusted savings of $44 (10.9%) per diabetic member per month. Hospital admissions per 1,000 diabetic member years decreased by 18%, and bed days fell by 21%. Patients with diabetes were more likely to get HbAlc tests, foot exams, eye exams, and cholesterol screenings while enrolled in the program. These data suggest that implementation of a comprehensive healthcare management program for people with diabetes can lead to substantial improvements in costs and clinical outcomes in the short-term. It is expected that improvements will increase over time, with continuing improvements in health status and a reduction in the number of future diabetic complications.

First-pass radionuclide cineangiography in diagnosis of coronary artery disease in patients older than 75 years: evaluation of sensitivity.

The sensitivity of first-pass radionuclide cineangiography in the detection of coronary artery disease was evaluated in 60 patients subdivided equally according to age younger than or older than 75 years. The mean age of group 1 (age > or = 75 years) was 80.2 years +/- 5.3, and the mean age in group 2 (age < 75 years) was 62.0 years +/- 6.4. Disease prevalence in group 1 was 87% versus 80% in group 2. Group 1 had higher prevalence of hypertension (67% vs 33%) and lower prevalence of typical angina pectoris (23% vs 55%). Overall sensitivity of first-pass radionuclide cineangiography in group 1 was 93% versus 97% in group 2. Older patients had significantly lower maximal heart rates, workloads, and exercise durations, and age correlations were significant for exercise heart rate, workload, and exercise duration. Failure to achieve an adequate exercise endpoint had significant effect on testing sensitivity only in the younger subjects (98% vs 60%), indicating that sensitivity of first-pass radionuclide cineangiography is age independent.

First-pass radionuclide cineangiography: a reevaluation of its sensitivity and limitations in the detection of significant coronary artery disease.

The sensitivity of first-pass cineangiography in the detection of significant coronary artery disease (CAD) was recently assessed in 33 patients. No normal controls were studied. Overall sensitivity was 86% with a predictive value of 83% and a 36% false-positive rate. Attainment of an adequate exercise end point increased sensitivity to 92%; failure to achieve this end point diminished sensitivity to 71%. Correlation between first-pass and contrast angiography ejection fractions was high (r = 0.88, p less than .005) with a moderate correlation in wall motion analysis (r = 0.58, p less than .005). The development or the intensification of a wall motion abnormality (WMA) was the single most sensitive indicator of CAD (84%). Presence of WMA plus failure of the ejection fraction to increase by 6% over baseline increased testing sensitivity to 89%. The mean WMA score for patients with CAD was 2.0 +/- 1.5 compared with 0.6 +/- 1.3 for those with normal study results (p less than .01). The first-pass method identified 4 subjects who subsequently had normal findings from catheterization. Data confirm testing sensitivity of the first-pass technique and underscore the apparent limitations of this modality in differentiation of patients with normal vasculature.

Outpatient dobutamine therapy: the rhyme and the riddle.

Advances in critical care medicine have increased survival for victims of myocardial infarction and other acute cardiac events so that increasingly patients are receiving long-term, labor-intensive, and costly medical care. Innovations in drug delivery systems and skyrocketing health care costs have fostered the growth of home health care which has blossomed into a $2.8 billion industry. There is evidence that outpatient dobutamine therapy produces definite physical and possibly psychological improvements of variable degree and duration. Hemodynamic improvements are generally associated with improvement in functional class, and the financial savings are recognizably substantial. However, three major problems confront therapies with beta-adrenergic agonists: tendency for tolerance, ventricular arrhythmias, and increased myocardial oxygen consumption. There is a dire need for establishment of exclusionary patient criteria and for risk stratification, as well as for development of a portable radionuclide nonimaging monitor. Given the current fund of knowledge, outpatient dobutamine therapy should be undertaken cautiously after meticulous patient selection reflecting an awareness of the tremendous complexities and inherent risks. The therapeutic implications are dependent on the nature of the underlying cardiomyopathy and the fact that beta-adrenergic receptor desensitization is unlikely to be overcome by progressive dosage increases. Therapy is initiated with the understanding that treatment will remain blindly empirical and conjectural in the absence of a continuous physiologic monitor and an expanded comprehension of the molecular pathophysiology of the failing ventricle.

Relapsing native-valve enterococcal endocarditis: a unique cure with oral ciprofloxacin combination drug therapy.

Enterococcal endocarditis is the third most common presentation in native valves, and it is the most refractory. Unique among the streptococci, enterococci are relatively resistant to beta-lactam antibiotics requiring a combination aminoglycoside regimen for cure. Relapse is common even after apparently adequate therapy and may be seen in up to 25% of cases that involve streptomycin-resistant strains. This problem is magnified by the recent appearance of beta-lactamase-producing strains of S. faecalis resistant to both ampicillin and gentamicin. Ciprofloxacin is being investigated with a number of antimicrobials in the attempt to identify superior protocols against troublesome pathogens. However, little published data is available concerning the clinical efficacy of this drug in enterococcal endocarditis. In vitro studies and preliminary trials with animal models have generally been disappointing with broth macrodilution time-kill or agar dilution proving the most reliable in vitro methods for predicting in vivo outcomes. The urgent need to identify new combination drug regimens is underscored not only by the development of new resistance patterns, but by the well-documented toxicities of conventional therapies. The authors present a case of relapsing enterococcal endocarditis caused by a non-beta-lactamase-producing strain of S. faecalis, which demonstrated high-level resistance to streptomycin but not to gentamicin. Relapses occurred despite favorable laboratory data and aggressive beta-lactam-gentamicin therapies. Cure was achieved using oral ciprofloxacin in a combination drug regimen, which is reported here for the first time.

Accuracy of flexible fiberoptic endoscopy in identifying abnormal endotracheal tube positions.

This study was carried out to investigate the accuracy of a simple, nonmaneuverable, flexible fiberoptic catheter in identifying both normal and abnormal endotracheal tube (ETT) positions. In addition, the utility of flexible fiberoptic endoscopy (FFE) for ETT position determination in inexperienced hands was examined. One adult dog was sedated and instrumented in the esophagus and trachea with identical ETTs. Four possible ETT positions (trachea, carina, bronchus, esophagus) were randomly assigned. One investigator positioned the ETT into the assigned position by fluoroscopy. Four other blinded investigators were asked to determine the ETT position using the fiberoptic catheter. Each blinded investigator was given 15 seconds to complete the examination and record the ETT position. Randomization resulted in 25 ETT positions examined by each of the four blinded investigators for a total of 100 FFE determinations. FFE ETT determination was correct in 97% of the examinations. All esophageal intubations were correctly identified. Two tracheal locations were misdiagnosed as carina and bronchial, while one carinal location was incorrectly judged as tracheal. The sensitivity of FFE ETT localization was 91.7%, and the specificity was 98.6%. There was no difference in performance by investigator training level or endoscopy experience. We conclude that FFE is a rapid and accurate method for determining both normal and abnormal ETT locations. ETT position determination can be confidently performed by health professionals with minimal training.

Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume-resuscitated nonsurgical patients.

We examined the cardiovascular and metabolic response to RBC transfusion in patients with circulatory shock after volume resuscitation. Data were analyzed from 36 transfusions in 32 patients who were undergoing continuous hemodynamic monitoring. Transfusions were administered for moderate to severe anemia, mean Hgb 8.3 g/dl. The diagnosis were sepsis (19/36), cardiogenic shock (14/36), connective tissue disease (2/36), and severe hypocalcemia (1/36). Benefit from transfusion was defined as an improvement in tissue oxygen utilization (increased oxygen consumption [VO2] or decreased lactate), a decrease in myocardial VO2 (MAP x HR), or a decrease in myocardial work (left ventricular work index). Mean transfusion volume was 577 ml over 4.5 h. Hgb and oxygen delivery (DO2) increased by 27% and 28%, respectively, while pulmonary artery wedge pressure and cardiac index were unchanged. No significant change was noted in VO2, or lactate, after augmentation of red cell mass. An increase occurred in myocardial work indices and MAP x HR. No changes were identified when subgroups were analyzed based on diagnosis, pretransfusion Hgb, lactate, or VO2 levels. We conclude that selective increase in DO2 by augmentation of RBC mass and oxygen-carrying capacity did not improve the shock state in these volume-resuscitated patients, regardless of the etiology of the shock.

Effect of red cell transfusion on oxygen consumption following fluid resuscitation in septic shock.

Previous studies have shown that fluid resuscitation in septic shock improves oxygen consumption. Red cell transfusion during resuscitation from septic shock has also been shown to enhance oxygen consumption in patients with elevated lactate levels. This study investigates the effect of increasing oxygen delivery (DO2) through an isolated increase in arterial oxygen content following adequate fluid resuscitation from septic shock in humans. Nineteen patients receiving red cell transfusion (591 +/- 55 SEM ml) were monitored for changes in hemodynamic and oxygen utilization variables before and after transfusion. Transfusion resulted in a significant increase in hemoglobin (8.3 +/- 0.3 to 10.7 +/- 0.3 g.dl-1) and DO2 (483 +/- 29 to 621 +/- 32 ml.min-1.m-2). No increase in cardiac output or pulmonary artery wedge pressure (PAWP) resulted from the transfusion. In spite of the increase in delivery, there was no increase in oxygen consumption (VO2) or decrease in lactate. Subset analysis revealed that a pretransfusion oxygen extraction ratio under 24% was associated with an increase in VO2, but the pretransfusion level of cardiac index, PAWP, lactate, or VO2 was not. An isolated increase in arterial oxygen content as a means of increasing DO2 does not improve VO2 in septic shock following adequate fluid resuscitation. Patients with a low oxygen extraction ratio (less than 24%) represent a subset of patients which did improve consumption with transfusion, and may represent a more severe microcirculatory disturbance not amenable to fluid loading.

Effects of gas leak around endotracheal tubes on indirect calorimetry measurement.

The use of uncuffed endotracheal tubes (ETT) in pediatric patients raises concern over the accuracy of indirect calorimetry measurement in the presence of a gas leak around an ETT. We examined the effects of ETT gas leak on respiratory gas measurements in a dog model. Mongrel dogs (n = 12) were sedated, paralyzed, intubated, and placed on mechanical ventilation. Leak was achieved by adjusting cuff volume. Oxygen consumption (VO2), CO2 production (VCO2), respiratory exchange ratio (RER), and resting energy expenditure (REE) were measured at each leak pressure (Pleak). Peak inspiratory pressure (PIP), Pleak, inspiratory and expiratory tidal volume (VTinsp, VTexp), VE, end tidal CO2 (ETCO2), and blood gases were recorded at each leak pressure. VO2, VCO, and REE decreased significantly with increasing gas leak. There was a linear relationship between VO2, VCO2, and REE with both TVratio (VTexp/VTinsp) and Pdiff (PIP-Pleak). Multiple regression equations based on TVratio and Pdiff were obtained which allowed correction of the measurement error in VO2, VCO2, and REE, with correlation coefficients (R2) of 0.71, 0.75, and 0.73, respectively. ETT gas leak affects measurements of VO2, VCO2, and REE, but not RER. Measurements made with TVratio greater than 0.80 required no correction. Measurements made with TVratio greater than 0.45 could be corrected to actual values in our model with regression equations based on TVratio and Pdiff. We conclude that indirect calorimetry measurements can be useful in the presence of tracheal gas leak around an ETT.

Endobronchial tuberculosis manifested as obstructive airway disease in a 4-month-old infant.

Tuberculosis is becoming a more prominent pediatric disease, but there are few recent reports of endobronchial involvement. We have presented the case of a 4-month-old infant with symptomatic obstructive airway disease due to Mycobacterium tuberculosis. Endobronchial tuberculosis usually follows 2 to 3 months of antituberculous therapy. This case is especially unusual because the endobronchial disease developed before diagnosis or therapy. Endobronchial tuberculosis should be considered in any patient with symptoms or roentgenographic findings of obstructive airway disease. Bronchoscopy is the best technique for diagnosis and follow-up of endobronchial tuberculosis.

Thyroid hormone metabolism and level of illness severity in pediatric cardiac surgery patients.

To define better the temporal relationship between alterations in thyroid hormone metabolism and changes in illness severity, we studied thyroid function in 12 children preoperatively and at 2, 12, 24, 48, and 72 hours after cardiac surgery. We then compared these findings with illness severity as assessed by a modification of the Therapeutic Intervention Scoring System (TISS). All patients had significant (p less than 0.01) reduction in serum T3 (mean 35% of baseline levels) and elevation in serum rT3 (mean 237% of baseline levels) in the postoperative period. Average correlation coefficients for the combined data were as follows: TISS and T3 levels, -0.63 +/- 0.17; TISS and rT3 levels, 0.51 +/- 0.18. Examination of individual patient data normalized to preoperative T3 and rT3 levels and compared with TISS scores demonstrated a lag in alterations of serum rT3 and T3 levels relative to illness severity during recovery from cardiac surgery. We conclude (1) the euthyroid sick syndrome occurs in all pediatric cardiac surgery patients, regardless of procedure complexity, (2) changes in rT3 levels parallel but follow changes in degree of therapeutic intervention, indicating that these alterations result from, and do not cause, increasing severity of illness, (3) rT3 levels return toward normal before T3 levels, which remain low beyond the critical postoperative period, and (4) clinical indicators of illness severity are fairly well inversely correlated with T3 levels, supporting an adaptive reduction in 5'-deiodinase activity during the postoperative period.

Use of flexible fiberoptic endoscopy for determination of endotracheal tube position in the pediatric patient.

Flexible fiberoptic endoscopy (FFE) was utilized in a series of 24 critically ill pediatric patients to determine the position of the endotracheal tube (ETT) tip relative to the carina. Training on a model system revealed no significant differences in predicting ETT-to-carina distance (ETT-C) with respect to operator, ETT size, or absolute ETT-C as measured directly. No significant differences in ETT-C could be determined between traditional bedside chest x-ray (CXR) or FFE when FFE was performed on intubated pediatric ICU patients. A correlation coefficient comparing the two methods was 0.767. Neither ETT size nor FFE operator affected this correlation. Although used as the gold standard, CXR failed to demonstrate the carina clearly in 15 patients. FFE delineated the carina clearly in 22 patients. Ability to visualize ETT placement within the trachea was essentially identical for FFE (22/24) compared to CXR (23/24). However, the time required to obtain this information was significantly different: 30.6 min (range 13 to 57) for CXR; 40 sec (range 16 to 94) for FFE. No clinically significant changes in patient pulse oximetry, heart rate, or physical exam were observed during FFE. Only copious secretions impaired the utility of FFE. We concluded that FFE is a safe, fast, easily learned method to determine relative ETT position or precise ETT-C in the mechanically ventilated pediatric patient.

Use of a single silastic i.v. catheter for cystic fibrosis pulmonary exacerbations.

Use of a single percutaneous silastic IV catheter for cystic fibrosis hospitalizations was evaluated among 23 patients during 45 hospitalizations. Patients ages ranged from 4 to 20 years and weights from 18 to 60 kg. Percutaneous silastic catheters were used for infusion of all IV antibiotics and IV fluids. Catheters remained in place for a total of 549 patient days (mean 12.2, range 2-34). No patient demonstrated clinical signs of local infection or sepsis. Thirty six catheters served as the single IV access for a patient's entire hospitalization. Nine catheters were removed because of discomfort, obstruction, or mechanical dysfunction before the conclusion of the hospitalization. A single, percutaneously placed silastic catheter appears to be a safe and effective way of maintaining IV access throughout the duration of hospitalization for cystic fibrosis exacerbations.