Using Visual Analytics to Determine the Utilization of Preoperative Anesthesia Assessments.

BACKGROUND: Preoperative assessments are a required and essential element of anesthetic care, yet little is known about the utilization of these documents by clinicians who are not part of the anesthesia care team. As part of perioperative workflow restructuring, we implemented a data visualization technique of electronic medical record audit log data to understand the utilization of preoperative anesthesia assessments by non-anesthesia personnel. METHODS: An audit log cache containing 140 days of data was queried for all accesses of preoperative anesthesia assessment documents for any patient who had a preoperative anesthesia assessment that was accessed during that period. User roles were aggregated into categories. Descriptive statistics and data visualization were generated using R (R Software Foundation, Vienna, Austria). Comparisons were performed with the Wilcoxon signed rank test with continuity correction. RESULTS: During the study period, 73 802 (0.015%) of the 485 062 902 audit log accesses were preoperative anesthesia assessments representing 412 departments, 302 user roles, and 3 916 distinct users who accessed preoperative anesthesia assessments from 14 235 surgical cases. Each assessment was accessed 2.9 times on average. Assessments performed in the preoperative anesthesia assessment clinic were accessed more frequently than those created on the day of surgery in the preoperative holding room (3.58 ± 5.18 v. 1.98 ± 1.76 average views; p<0.0001). We observed accesses of these documents by pathology and general surgery researchers, as well as orthopedics attending physicians accessing documents that were two years old. CONCLUSIONS: This approach revealed patterns of utilization that had not been previously identified, including usage by surgical residents, surgical faculty, and pathology researchers both before and after the surgical event for which the documents are generated. Knowledge of these dependencies directly informed perioperative workflow restructuring efforts. This visual analytic approach could be broadly utilized to understand documentation dependencies in a variety of clinical contexts.

Comparison of a step-down dose of once-daily ciclesonide with a continued dose of twice-daily fluticasone propionate in maintaining control of asthma.

OBJECTIVE: To compare a step-down approach in well-controlled asthma patients, as recommended by treatment guidelines, from fluticasone propionate 250 microg twice daily (FP250 BID), or equivalent, to ciclesonide 160 microg once daily (CIC160 OD) with continued FP250 BID treatment. RESEARCH DESIGN AND METHODS: Patients with well-controlled asthma prior to study entry were included in two identical, randomized, double-blind, double-dummy, parallel-group studies. After a 2-week run-in period with FP250 BID, patients were randomized to CIC160 OD (n = 58) or FP250 BID (n = 53) for 12 weeks. Primary endpoints were percentage of days with asthma control, asthma symptom-free days, rescue medication-free days and nocturnal awakening-free days. Secondary endpoints included lung function variables, asthma symptom scores, rescue medication use and asthma exacerbations. Safety variables were also recorded. RESULTS: Patients had >or= 97% of days with asthma control, 98% asthma symptom-free days and 100% of days free from rescue medication use and nocturnal awakenings in both treatment groups (median values). There were no significant between-treatment differences for any of the primary or secondary efficacy variables. Overall, 42 treatment-emergent adverse events (TEAEs) were reported in the CIC160 OD group and 49 TEAEs were reported in the FP250 BID group. There were no clinically relevant changes from baseline in the safety variables in either treatment group. CONCLUSIONS: Patients well controlled on FP250 BID, or equivalent, who were stepped down to CIC160 OD, maintained similar asthma control compared with patients who received continued treatment standardized to FP250 BID.

Transient and partial effect of high-dose intravenous immunoglobulin in polyarteritis nodosa.

A 57-year-old male patient suffered from polyarteritis nodosa. He presented with articular pain, polyneuropathy, subcutaneous nodules and nodes on the lower legs. After several immunosuppressive agents (methotrexate, mycophenolate mofetil and prednisolone) had proven to be ineffective, 2 g intravenous immunoglobulin (IVIG) per kilogram body weight were administered within 2 days in combination with 10 mg prednisolone per day. Subsequently, 6 cycles of IVIG were applied in increasing intervals from 4 to 6 weeks resulting in a minimum dosage of 0.33 g/kg/week IVIG. The polyarteritis improved within a few days after the first IVIG application. The intensity of polyneuropathy and arthralgia of polyarteritis decreased during the period of IVIG treatment. Finally, a dose reduction of less than 0.25 g/kg/week IVIG resulted in recurring polyarteritis nodosa, which could not be controlled by further administration of IVIG. Therefore, our data indicate that: (1) IVIG is partially effective in cases of polyarteritis nodosa, but the therapeutic effect is only transient; (2) the success of treatment may be correlated with the dose of IVIG per body weight and week; (3) the efficacy/cost ratio of IVIG in polyarteritis nodosa appears to be low.

Effects of low dose ultraviolet A-1 phototherapy on morphea.

AIM: The effects of low dose ultraviolet A-1 (UVA-1) phototherapy on different clinical stages of morphea (localized scleroderma) were analyzed in this case study. Based on these data, the different types of phototherapy described in the literature and currently used for treatment of morphea are compared. METHODS: Three patients with severe plaque type morphea in different stages were studied: one patient with late-stage lesions having stable sclerotic plaques; another patient with active inflammatory lesions; and a third patient with late-stage lesions associated with overlying lichen sclerosus et atrophicus (LSA). The treatment given was low dose UVA-1 phototherapy with single doses of 20 J/cm2 administered four times a week for 6 weeks, and once a week for another 6 weeks. RESULTS: Following UVA-1 phototherapy, the sclerotic plaques resolved, leaving smooth and soft tanned skin with normal structure, consistency and folding capability. In morphea with overlying LSA the elastic fibers did not completely return to the superficial papillary dermis despite the clinical clearance of both morphea and LSA. These data suggest that low dose UVA-1 phototherapy may improve, but not completely reverse, the histopathological changes of LSA. No side effects were observed during or after treatment. CONCLUSION: Our observations show in three patients that low-dose UVA-1 phototherapy is highly effective for treatment of all stages of morphea, including early inflammatory and late sclerotic lesions, and morphea with overlying lichen sclerosus et atrophicus. Because of its safety and efficacy, low dose UVA-1 phototherapy appears to be the treatment modality of choice.

Subcellular localization of the human proto-oncogene protein DEK.

Recent data revealed that DEK associates with splicing complexes through interactions mediated by serine/arginine-repeat proteins. However, the DEK protein has also been shown to change the topology of DNA in chromatin in vitro. This could indicate that the DEK protein resides on cellular chromatin. To investigate the in vivo localization of DEK, we performed cell fractionation studies, immunolabeling, and micrococcal nuclease digestion analysis. Most of the DEK protein was found to be released by DNase treatment of nuclei, and only a small amount by treatment with RNase. Furthermore, micrococcal nuclease digestion of nuclei followed by glycerol gradient sedimentation revealed that DEK co-sedimentates with oligonucleosomes, clearly demonstrating that DEK is associated with chromatin in vivo. Additional chromatin fractionation studies, based on the different accessibilities to micrococcal nuclease, showed that DEK is associated both with extended, genetically active and more densely organized, inactive chromatin. We found no significant change in the amount and localization of DEK in cells that synchronously traversed the cell cycle. In summary these data demonstrate that the major portion of DEK is associated with chromatin in vivo and suggest that it might play a role in chromatin architecture.

Role of cadherins and matrixins in melanoma.

Cancer is generally viewed as the result of disrupted intra-and intercellular homeostatic regulation. Once the homeostatic balance is lost and malignant transformation has occurred, microenvironmental factors such as degradation of matrix components and host-tumor interactions are essential for survival and growth of malignant cells. Within the previous year, cadherins and matrixins (matrix metalloproteinases) have emerged as key factors in these processes. The pathways involved are interconnected and detailed knowledge about the biologic significance of each member in a given pathway is essential for our understanding of oncogenesis. Restoration of E-cadherin-mediated control over melanoma cells and modulation of the involved regulation pathways are promising novel therapeutic strategies. Another approach is the rational design of inhibitors that perturb matrix metalloproteinases in a particular cell type and interrupt tumor-specific proteinase activation cascades. Advances in these fields will lead to the development of better tools for prevention, diagnosis, and therapy.

Rapid response of IgA pemphigus of subcorneal pustular dermatosis type to treatment with isotretinoin.

Diagnosing IgA pemphigus and distinguishing between its 2 subtypes, intraepidermal neutrophilic IgA dermatosis type and subcorneal pustular dermatosis type, is important because treatment of IgA pemphigus has to be different from treatment of other blistering autoimmune dermatoses. We present a patient with subcorneal pustular dermatosis type of IgA pemphigus who rapidly responded to systemic treatment with isotretinoin. Specific diagnosis was established by detecting IgA serum activity to desmocollin 1 by indirect immunofluorescence microscopy on unfixed COS7 cells transfected with desmocollin 1. No IgA or IgG serum reactivity was found to recombinant forms of desmogleins 1 and 3 by an antigen-specific enzyme-linked immunosorbent assay. The disease was not effectively controlled by conventional therapeutic regimens. Systemic treatment with isotretinoin 20 mg daily led to complete clearance of skin lesions within 3 weeks. Assaying IgA serum reactivity to desmocollin 1, desmoglein 1, and desmoglein 3 as a valuable method for establishing the diagnosis and differentiating the 2 subtypes of IgA pemphigus. Isotretinoin was an effective drug in the treatment of subcorneal pustular dermatosis type of IgA pemphigus in this patient.

The protein encoded by the proto-oncogene DEK changes the topology of chromatin and reduces the efficiency of DNA replication in a chromatin-specific manner.

The structure of chromatin regulates the genetic activity of the underlying DNA sequence. We report here that the protein encoded by the proto-oncogene DEK, which is involved in acute myelogenous leukemia, induces alterations of the superhelical density of DNA in chromatin. The change in topology is observed with chromatin but not with naked DNA and does not involve dissociation of core histones from chromatin. Moreover, these effects require histone H2A/H2B dimers in addition to histone H3/H4. We additionally tested whether the DEK protein affects DNA-utilizing processes and found that the DEK protein substantially reduces the replication efficiency of chromatin but not of naked DNA templates.

Histone octamer dissociation is not required for in vitro replication of simian virus 40 minichromosomes.

Replication of chromosomal templates requires the passage of the replication machinery through nucleosomally organized DNA. To gain further insights into these processes we have used chromatin that was reconstituted with dimethyl suberimidate-cross-linked histone octamers as template in the SV40 in vitro replication system. By supercoiling analysis we found that cross-linked histone octamers were reconstituted with the same kinetic and efficiency as control octamers. Minichromosomes with cross-linked nucleosomes were completely replicated, although the efficiency of replication was lower compared with control chromatin. Analysis of the chromatin structure of the replicated DNA revealed that the cross-linked octamer is transferred to the daughter strands. Thus, our data imply that histone octamer dissociation is not a prerequisite for the passage of the replication machinery and the transfer of the parental nucleosomes.

Assessment of minimal phototoxic dose following 8-methoxypsoralen bath: maximal reaction on average after 5 days.

An essential procedure before starting bath psoralen ultraviolet (UV) A (PUVA) photochemotherapy is the evaluation of the minimal phototoxic dose (MPD), which is traditionally assessed 3 days after irradiation. However, there are no controlled studies supporting the 72 h peak of bath-PUVA erythema. The aim of this study was therefore to determine the exact time course of the erythematous reaction in human skin following bath-PUVA. For this purpose, the skin of 10 volunteers was exposed to 0.5-3.0 J/cm2 UVA directly after a 20-min 8-methoxypsoralen bath (0.5 mg/L, 37 degrees C). At 24, 48, 72, 96, 120 and 144 h (1-6 days) after irradiation, the MPD and the erythema sum score (ESS) were determined in each subject. The results showed a maximal erythematous reaction on average 5 days after irradiation. The mean MPD gradually decreased from day 2 (> 3.0 J/cm2) to day 5 (mean +/- SD 1.15 +/- 0.63 J/cm2) and started to increase at day 6 (mean +/- SD 1.6 +/- 0.52 J/cm2). The mean +/- SD ESS correspondingly increased from day 2 (0 +/- 0) to day 5 (10.5 +/- 3. 7) with a decrease at day 6 (7.5 +/- 3.1) (difference between day 3 and beyond statistically significant at P < 0.05). As our study indicates a maximal erythematous reaction to the bath-PUVA up to 5 days after irradiation, the traditional MPD assessment at 3 days generates a risk of phototoxic side-effects within the phototherapy course by underestimating the phototoxic effect in some patients. These findings contribute towards a more defined understanding of the kinetics of the phototoxic reaction in bath-PUVA therapy.

Large T-antigen double hexamers imaged at the simian virus 40 origin of replication.

The initial step of simian virus 40 (SV40) DNA replication is the binding of the large tumor antigen (T-Ag) to the SV40 core origin. In the presence of Mg(2+) and ATP, T-Ag forms a double-hexamer complex covering the complete core origin. By using electron microscopy and negative staining, we visualized for the first time T-Ag double hexamers bound to the SV40 origin. Image processing of side views of these nucleoprotein complexes revealed bilobed particles 24 nm long and 8 to 12 nm wide, which indicates that the two T-Ag hexamers are oriented head to head. Taking into account all of the biochemical data known on the T-Ag-DNA interactions at the replication origin, we present a model in which the DNA passes through the inner channel of both hexamers. In addition, we describe a previously undetected structural domain of the T-Ag hexamer and thereby amend the previously published dimensions of the T-Ag hexamer. This domain we have determined to be the DNA-binding domain of T-Ag.

Chronic sclerodermic graft-versus-host disease refractory to immunosuppressive treatment responds to UVA1 phototherapy.

Graft-versus-host disease is a frequent complication of allogenic bone marrow transplantation. Approximately 10% of patients suffering from chronic graft-versus-host disease develop sclerodermic graft-versus-host disease of the skin, which often does not respond to conventional immunosuppressive therapy. An alternative to immunosuppressive treatment is photochemotherapy. We describe a patient with chronic sclerodermic graft-versus-host disease who did not respond to a combination therapy of cyclosporine and prednisone and later mycophenolate mofetil plus prednisone. A combination therapy of mycophenolate mofetil (2 g/day) and low-dose UVA(1) therapy (single dose, 20 J/cm(2), 4 times per week over 6 weeks) resulted in striking clinical improvement of sclerodermic graft-versus-host disease.

Left atrial myxomas presenting with right hand weakness.

A 63-year-old man with multiple left atrial myxomas presenting with right hand weakness is described. Two-dimensional echocardiography obtained during the evaluation for his stroke showed a large left atrial mass. At surgery, two separate left atrial myxomas were excised. Pathology confirmed the diagnosis. Although left atrial myxomas are uncommon, they should be included in the differential diagnosis of stroke, especially in patients who present without cardiovascular or cerebrovascular risk factors. The absence of cardiac symptoms and signs does not rule out a cardiac myxoma.

PUVA-bath photochemotherapy (PUVA-soak therapy) of recalcitrant dermatoses of the palms and soles.

PUVA-bath therapy has proven to avoid many side effects associated with oral 8-methoxypsoralen (8-MOP) treatment. In order to investigate the effectiveness of topical PUVA-bath therapy (PUVA-soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque-type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA-soak using 8-MOP. No additional treatment except skin moisturising cream such as unguentum emulsificans aquosum was used during the study period. The single UVA-doses applied ranged from 0.3 to 3.0 J/cm2 (mean single dose of 1.8 J/cm2), with a mean cumulative dose of 48.6 J/cm2 per patient. Altogether 26 of 30 patients responded well within 8 weeks of treatment with 63% of all patients showing a complete remission and 23% showing considerable improvement, as shown by flattening of plaques, decreased scaling and erythema, as well as decreased vesicle and pustule formation. The condition responding best to our therapy was palmoplantar psoriasis followed by atopic eczema. Hyperkeratotic dermatitis displayed the poorest responding rates in this study. Unwanted side effects such as erythema, pain, blistering or patchy hyperpigmentation were not observed in any of the patients. We conclude that PUVA-soak therapy can be highly efficient in the treatment of palmoplantar dermatoses, especially in the management of palmoplantar psoriasis.

[Severe course of a mutilating pansclerotic circumscribed scleroderma in childhood. Clinical aspects and therapy]. / Schwerer Verlauf einer mutilierenden pansklerotischen zirkumskripten Sklerodermie im Kindesalter. Klinik und Therapie.

Disabling pansclerotic morphea of childhood is the most severe variant of localized scleroderma. It is characterized by rapid progression of deep cutaneous fibrosis expanding over large areas of body surface. The prognosis in terms of normal life activity is poor and the disease may even take a fatal course. Presented is a case with extremely severe and rapidly progressive lesions resulting in cutaneous ulcerations joint contractures, and multilaing deformities of the extremities. Histopathological analysis revealed extensive intravascular calcinosis of the small vessels, which may be an important factor in the pathogenesis of this poorly understood disease. UVA1-phototherapy was performed and induced a softening of sclerosis and a distinct decrease of skin thickness. Based on these observations UVA1-phototherapy may be promising in the treatment of extensive sclerotic disease of this kind, and possibly other diseases accompanied by excessive sclerosis.

Deficiency of a novel retinoblastoma binding protein 2-homolog is a consistent feature of sporadic human melanoma skin cancer.

Using RNA arbitrarily primed PCR, the authors selected for transcripts with cell cycle-related differential expression in cultured human melanocytes. Among the partial cDNAs cloned, a novel cDNA was identified, which showed 54% identity to the recently cloned cDNA of the retinoblastoma binding protein-2 (RBP2). The 6.5-kB full-length cDNA of this RBP2-related gene, termed RBP2 homolog 1 (RBP2-H1), was obtained from a human teratocarcinoma cDNA library. Two independent libraries from human malignant melanomas were negative. A computerized sequence analysis revealed highly conserved motifs with possible functional meaning: two domains that, in the RBP2 homolog, mediate the binding and interaction with the proteins encoded by the retinoblastoma susceptibility gene, the TATA-binding protein, and the oncoprotein rhombotin 2; in addition, two DNA-binding zinc finger/leukemia-associated protein motifs were detected. Because a functional role in cell-cycle control and transcriptional activation can be envisioned, we investigated the expression of this novel transcript in normal fetal and adult tissues, as well as tissues of benign and malignant melanocytic tumors. By conducting multiple Northern blot, RT-PCR, and in situ hybridization analyses, the authors showed that the corresponding mRNA is expressed in virtually all normal tissues. Accordingly, they found RBP2-H1 expression in microdissected tissue samples from benign melanocytic nevi (n = 10). In contrast, the transcript is significantly down-regulated or even lost in tissue samples from human malignant melanomas (n = 13), melanoma metastases (n = 10), and melanoma cell lines (n = 7). The authors concluded that the loss or down-regulation of RBP2-H1 expression could be a useful molecular marker for a transformed phenotype in the human melanocytic system.

Involvement of topoisomerases in the initiation of simian virus 40 minichromosome replication.

Topoisomerases provide the unlinking activity necessary for replication fork movement during DNA replication. It is uncertain, however, whether topoisomerases are also required for the initiation of replication. To investigate this point, we have performed pulse-chase experiments with SV40 minichromosomes as template to distinguish between the initiation and the elongation of replication. Using an unfractionated cytosolic extract as a source of replication functions, we found that the addition of topoisomerases at the initiation step significantly increased the number of active chromatin templates, whereas addition of topoisomerases at the elongation step had only minor effects. Minichromosomes with an extended chromatin structure as well as protein-free DNA required less topoisomerase for effective replication initiation. We could exclude the possibility that topoisomerases enhance the origin binding of T antigen, the SV40 replication initiator, and propose instead that the arrangement of nucleosomes influences the diffusion of supercoils during initial DNA unwinding. Efficient initiation therefore requires a high local concentration of topoisomerases to relax the torsional stress.

Effects of water temperature on photosensitization in bath-PUVA therapy with 8-methoxypsoralen.

The pharmacokinetic aspects of bath-PUVA are not completely clarified. Therefore, we determined the phototoxic response of human skin following psoralen baths at temperatures ranging from 32 degrees C to 42 degrees C (71.6-107.6 degrees F) and UVA doses ranging from 0.5 to 5.5 J/cm2. The highest therapeutical photosensitization (i.e., lowest minimal phototoxic dose) was assessed at temperatures of 37 degrees C (98.6 degrees F) and above. Photosensitization was significantly decreased at lower temperatures. These data indicate that a bath temperature of 37 degrees C (98.6 degrees F) should be used to gain optimal therapeutic efficiency in a clinical setting. Furthermore, in order to minimize the risk of adverse phototoxic effects in bath-PUVA, it is important to use a constant temperature during the psoralen bath.