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Background: Instability is a common complication after revision total hip arthroplasty. Tripolar constrained (TC) and dual mobility (DM) liners cemented into tantalum acetabular revision (TM) shells are established alternatives that reduce instability risk. This study compares outcomes of TC and DM liners cemented into TM shells in complex revision hip replacements. Methods: Fifty cases using a TM shell and a TC or DM cemented liner with at least 12 months of follow-up were identified. There were 25 TC and 25 DM liners. Clinical, radiographic, and patient-reported outcomes were collected. Reasons for re-revision and failures were analyzed. Results: The average age was 73 years in the TC group and 75 years in the DM group. The median follow-up duration was 50 months (23 - 96) and 13 months (12 – 21) for the TC and DM groups, respectively. The mean Harris Hip Score improved from 37 to 61 for the TC group and from 51 to 73 in the DM group at the last review. Two TC cases required revision for wear and liner failure. One DM insert was changed at reoperation for periprosthetic femur fracture. There were no failures of cement fixation in either group and no revisions for cup loosening. Conclusions: In complex revision hip replacement with a history of instability or judged to have a high risk of instability postoperatively, TC and DM liners cemented into tantalum revision shells are both successful, giving acceptable results. The improved arc of movement with DM liners, minimizing impingement, makes them preferable except when there is a global abductor deficiency or severe joint laxity.

Background: The American Academy of Orthopaedic Surgeons (AAOS) Appropriate Use Criteria (AUC) for Surgical Management of Osteoarthritis of the Knee (2016) and Management of Osteoarthritis of the Hip (2017) are intended to provide treatment recommendations for osteoarthritis (OA). This study examined the agreement of AUC appropriateness classifications with arthroplasty surgeon recommendations for total knee arthroplasty (TKA) and total hip arthroplasty (THA)., Methods: The cohort included 558 OA patients (397 knee, 161 hip) referred to a specialty arthroplasty clinic. Surgeons completed the online AAOS AUC patient profiles to generate appropriateness ratings. Surgeons' recommendations for treatment were recorded. We performed univariate and bivariate analyses to evaluate relationships between AUC appropriateness and surgeon recommendations., Results: The knee OA AUC classified TKA as "appropriate" for 309 (77.8%) of the 397 knee OA patients. Surgeons recommended TKA for 123 (31.0%), resulting in 46.8% (n = 186) higher rate of "appropriate" classification by AUC than TKA recommendation by surgeons. Weighted Cohen's κ demonstrated slight agreement (κ = 0.06, 95% confidence interval: 0.04, 0.09) between AUC appropriateness and surgeon TKA recommendation. The hip OA AUC classified THA as "appropriate" for 98 (60.9%) of the 161 hip OA patients. Surgeons recommended THA for 76 (47.2%), resulting in 13.7% (n = 22) higher rate of "appropriate" classification by AUC than THA recommendation by surgeons. Weighted Cohen's κ demonstrated moderate agreement (κ = 0.47, 95% confidence interval: 0.37, 0.57) between the AUC appropriateness classification and the surgeon's THA recommendation., Conclusions: AAOS AUC guidelines indicated surgical appropriateness significantly more than arthroplasty surgeons. AUC agreed slightly with surgeons for TKA and moderately for THA., (© 2024 The Authors.)

To explore the carbon sequestration potential of hardwood forests in the eastern United States, the forest vegetation simulator (FVS) and life cycle assessment (LCA) were integrated to analyze the forest carbon dynamics for the four subregions of the eastern United States: northeast (NE), mid-Atlantic (MA), southeast (SE), and north central (NC). This study quantitatively assessed current forest management practices for timber production and their associated life-cycle environmental impacts. The system boundary was selected to be consistent with the A1 module (extraction and upstream production) required by an Environmental Product Declaration (EPD) for wood products. The results indicate that uneven-aged (UA) forest management yields higher carbon stocks and growth than even-aged (EA) management across all subregions. In contrast, clearcutting under EA management results in higher carbon removal. It was found that fuel consumption-related greenhouse gas (GHG) emissions for manual and mechanized harvesting systems for both management types ranged between 9.13 and 12.15 kg of CO 2 equivalent per cubic meter (kg CO 2 e/m 3 ), with an average of 11 kg CO 2 e/m 3 of hardwood timber harvested across all subregions. It is estimated that 63-187 megajoules (MJ) of energy is needed to produce 1 m 3 of hardwood sawlogs. The extraction and loading processes contributed more to the total GHG emissions than the felling and processing within the system boundary. The study concludes that UA management led to higher forest carbon and net carbon balance (excluding carbon stock) compared to EA management in the eastern U.S. hardwood forests. Forest management strategies should be determined based on the ecological goal of increasing forest carbon stock and the economic goal of maximizing revenue from the timber market. The findings of this study have implications for policymakers and forest managers in mitigating climate change and carbon sequestration through sustainable forest management for timber production., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Following life-cycle assessment (LCA) methodology, this study presents a state-level estimation of embodied carbon of wood products harvested in 2019 from California and subsequently processed, manufactured, transported, used, and disposed at the end-of-life (EoL). In a conventional static approach to LCA, all GHG emissions were aggregated and considered to occur at year 0 of the given time horizon (500 years in this study) and used a static characterization factor (CF). In dynamic LCA, GHG emissions occurring in different years were considered, and their global warming impact (GWI) was determined using a time-dependent CF over the selected time horizon of 500 years. Four scenarios were developed to examine the impact of EoL choices on GWI. It was found that dynamic GWI for all scenarios ranged from 0.27 to 0.93 million tonne CO₂e, which were 45-73 % lower than those estimated with static LCA approach, indicating that the static LCA approach could lead to an underestimation of the benefits of substituting wood for non-wood products, compared to those based on dynamic LCA approach. This analysis also demonstrated that the choice of EoL treatment option is a key factor affecting the estimated GWI as it directly determines the annual emission of GHGs released into atmosphere and subsequently their warming effect depending on the time harvested wood products (HWPs) spend in the horizon of assessment. Overall, the dynamic LCA performed in this study enabled more robust interpretations of embodied carbon by including temporal boundaries associated with the HWPs life cycle., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Peeling skin syndromes form a large and heterogeneous group of inherited disorders characterized by superficial detachment of the epidermal cornified cell layers, often associated with inflammatory features. Here we report on a consanguineous family featuring noninflammatory peeling of the skin exacerbated by exposure to heat and mechanical stress. Whole exome sequencing revealed a homozygous nonsense mutation in FLG2, encoding filaggrin 2, which cosegregated with the disease phenotype in the family. The mutation was found to result in decreased FLG2 RNA levels as well as almost total absence of filaggrin 2 in the patient epidermis. Filaggrin 2 was found to be expressed throughout the cornified cell layers and to colocalize with corneodesmosin that plays a crucial role in maintaining cell-cell adhesion in this region of the epidermis. The absence of filaggrin 2 in the patient skin was associated with markedly decreased corneodesmosin expression, which may contribute to the peeling phenotype displayed by the patients. Accordingly, using the dispase dissociation assay, we showed that FLG2 downregulation interferes with keratinocyte cell-cell adhesion. Of particular interest, this effect was aggravated by temperature elevation, consistent with the clinical phenotype. Restoration of corneodesmosin levels by ectopic expression rescued cell-cell adhesion. Taken together, the present data suggest that filaggrin 2 is essential for normal cell-cell adhesion in the cornified cell layers., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Selectively flexible rings, Colvin-Galloway (CG) Future and Carpentier-Edwards (CE) Physio II, are used for annuloplasty during mitral valve repair to facilitate dynamic annular motion while preventing annular dilation. In this study, we assessed the extent and nature of the flexibility of these rings in vivo, which has not been objectively demonstrated., Methods: Three-dimensional transesophageal echocardiography was used intraoperatively to acquire data regarding dynamic motion of mitral annuli and annuloplasty rings in 33 patients undergoing mitral repair (15 CG Future and 18 CE Physio II) and in 15 control patients. Data were analyzed to assess the dynamic changes in annular geometry after implantation of selectively flexible rings., Results: After annuloplasty, there was an immediate and significant decrease in annular displacement (p < 0.001) and annular displacement velocity (p < 0.01). Dynamic change in multiple variables including anteroposterior diameter (p < 0.001) and annular area (p < 0.001) was also significantly depressed. In comparison with normal mitral valves, partially flexible rings allowed limited dynamic motion: percentage changes in anteroposterior diameter (p < 0.001), anterolateral posteromedial diameter (p < 0.001), and total circumference (p < 0.001) were significantly lower. Compared with each other, the two rings resulted in similar changes in anterior annulus length (p = 0.93), posterior annular length (p = 0.82), and annular area (p = 0.31)., Conclusions: Mitral annular dynamics were uniformly depressed after implantation of these rings. Selective flexibility could not be demonstrated in vivo using echocardiographic data., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Pemphigus vulgaris (PV) is a severe autoimmune blistering disease caused by anti-epithelial antibodies, leading to disruption of cell-cell adhesion. Although the disease is exceedingly rare worldwide, it is known to be relatively prevalent in Jewish populations. The low prevalence of the disease represents a significant obstacle to a genome-wide approach to the mapping of susceptibility genes. We reasoned that the study of a genetically homogeneous cohort characterized by a high prevalence of PV may help exposing associated signals while reducing spurious results due to population sub-structure. We performed a genome-wide association study using 300K single-nucleotide polymorphisms (SNPs) in a case-control study of 100 PV patients of Jewish descent and 397 matched control individuals, followed by replication of significantly associated SNPs in three additional cohorts of Jewish, Egyptian, and German origin. In addition to the major histocompatibility complex locus, a genomic segment on 8q11.23 that spans the ST18 gene was also found to be significantly associated with PV. This association was confirmed in the Jewish and Egyptian replication sets but not in the German sample, suggesting that ST18-associated variants may predispose to PV in a population-specific manner. ST18 regulates apoptosis and inflammation, two processes of direct relevance to the pathogenesis of PV. Further supporting the relevance of ST18 to PV, we found this gene to be overexpressed in the skin of PV patients as compared with healthy individuals.

The Kv1.3 channel is important in the activation and function of effector memory T cells. Recently, specific blockers of the Kv1.3 channel have been developed as a potential therapeutic option for diverse autoimmune diseases. In psoriatic lesions, most lymphocytes are memory effector T cells. The aim of the present study was to detect the expression of Kv1.3 channels in these cells in psoriatic lesions as well as in human psoriasiform skin grafts using the severe combined immunodeficient (SCID) mouse model. Histological and immunohistochemical staining for Kv1.3 expression and various inflammatory markers was performed in sections obtained from six psoriatic patients and 18 beige-SCID mice with psoriasiform human skin grafts. Six grafted mice were treated with Stichodactyla helianthus neurotoxin (ShK), a known Kv1.3 blocker. The results showed an increased number of Kv1.3+ cells in the psoriatic skin as well as in the psoriasiform skin grafts as compared with normal skin and normal skin grafts. Injections of ShK showed a marked therapeutic effect in three of six psoriasiform skin grafts. A significantly decreased number of Kv1.3+ cells was observed in the responders compared with the control grafts. This pilot study, although performed in a small number of mice, reveals the possible beneficial effect of Kv1.3 blockers in psoriasis patients.

Cutaneous pseudolymphoma refers to a heterogenous group of benign reactive T-cell or B-cell lymphoproliferative processes of diverse causes that simulate cutaneous lymphomas clinically and histologically. Pseudolymphomas may arise in response to a wide variety of foreign antigens, but most are idiopathic. Major advances have been made in the histologic classification, immunohistochemistry, and molecular studies of cutaneous pseudolymphoma. Although this enables a more precise differentiation from cutaneous lymphoma, a substantial number of patients still present in whom the differential diagnosis is difficult or impossible. Some evidence suggests that pseudolymphomas may progress to cutaneous lymphoma due to persistent antigenic stimulation. More compelling evidence is needed, especially when most cutaneous pseudolymphoma are not associated with known antigens and the differentiation from cutaneous lymphoma may be difficult; therefore, a careful approach should be used, and the antigenic stimulus should be removed whenever possible. A watchful follow-up is warranted in idiopathic cases, and consideration should always be given to surgical or medical therapy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) belongs to the IGFBP superfamily, which is involved in the regulation of IGF and insulin signaling. Recently, a global gene expression study revealed that IGFBP7 is downregulated in the psoriatic epidermis, with UVB phototherapy restoring its expression to normal. In the present study, we confirmed that IGFBP7 expression is decreased in psoriatic lesions. Given the previous data suggesting a role for IGFBP7 in the control of cancer cell growth, we investigated its involvement in the regulation of keratinocyte (KC) proliferation and differentiation, which are abnormal in psoriasis. To model IGFBP7 downregulation in vitro, we used IGFBP7-specific small interfering RNA or small hairpin RNA-expressing lentiviral vectors in HaCaT cells or primary human KCs. Downregulation of IGFBP7 was found to markedly enhance KC proliferation in both systems, was associated with a significant decrease in KC susceptibility to tumor necrosis factor-alpha-induced apoptosis, but did not affect senescence. Downregulation of IGFBP7 was also shown to block expression of genes associated with calcium-induced differentiation of human KCs. Finally, recombinant IGFBP7 was found to inhibit KC proliferation and enhanced their apoptosis. These data position IGFBP7 as a regulator of KC proliferation and differentiation, suggesting a potential role for this protein in the pathophysiology and treatment of hyperproliferative dermatoses such as psoriasis.

Background: It has been shown in experimental animal models that were extended to humans that during autoimmune conditions, the immune system generates beneficial autoantibody (auto Ab) response to a limited number of inflammatory mediators that drive the pathogenesis of the disease., Objective: To investigate the presence of auto Abs to cytokines and chemokines in psoriasis., Methods: Sera were obtained from patients with psoriasis (n=37), atopic dermatitis (AD) (n=18) and healthy volunteers (n=56). The titers of auto (Abs) to TNF-alpha, interferon-alpha (IFN-alpha), interleukin-17 (IL-17), and chemokines CCL2, CCL3 and CCL5 were determined using enzyme-linked immunosorbant assay. Neutralizing activities of high-titer auto Abs to TNF-alpha and IFN-alpha were determined using functional in vitro assays., Results: Highly significant increased titers of auto Abs to TNF-alpha and IFN-alpha were detected in patients with psoriasis compared with healthy subjects and patients with AD (mean titers more than fourfold). These auto Abs demonstrated some neutralizing activity in vitro, but their serum levels did not correlate with the intensity and duration of the disease and with phototherapy induced remissions. Significantly increased titers albeit to a lesser extent, of auto Abs to CCL3 were detected in AD., Conclusions: Psoriasis patients produce markedly increased levels of auto Abs to TNF-alpha and IFN-alpha which are two of the key cytokines in this disorder. The presence of these auto Abs which possess some neutralizing activity in vitro, may be an epiphenomenon or might play a role in attempting to suppress the ongoing inflammatory process.

Naegeli-Franceschetti-Jadassohn syndrome (NFJS) is a rare autosomal dominant disorder characterized by loss of dermatoglyphics, reticulate hyperpigmentation of the skin, palmoplantar keratoderma, abnormal sweating, and other developmental anomalies of the teeth, hair, and skin. We recently demonstrated that NFJS is caused by heterozygous nonsense or frameshift mutations in the E1/V1-encoding region of KRT14, but the mechanisms for their deleterious effects in NFJS remain elusive. In this study, we further expand the spectrum of NFJS-causing mutations and demonstrate that these mutations result in haploinsufficiency for keratin 14 (K14). As increased apoptotic activity was observed in the epidermal basal cell layer in NFJS patients and as previous data suggested that type I keratins may confer resistance to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in epithelial tissues, we assessed the effect of down-regulation of KRT14 expression on apoptotic activity in keratinocytes. Using a HaCaT cell-based assay, we found that decreased KRT14 expression is associated with increased susceptibility to TNF-alpha-induced apoptosis. This phenomenon was not observed when cells were cultured in the presence of doxycycline, a known negative regulator of TNF-alpha-dependant pro-apoptotic signaling. Collectively, our results indicate that NFJS results from haploinsufficiency for K14 and suggest that increased susceptibility of keratinocytes to pro-apoptotic signals may be involved in the pathogenesis of this ectodermal dysplasia syndrome.

Epidermolysis bullosa (EB) encompasses a large group of inherited blistering skin disorders caused by mutations in at least 10 genes. Numerous studies, mainly performed in European and US families with EB, have revealed a number of characteristic epidemiological and genetic features, which form the basis for current diagnostic and counseling strategies. However, little is currently known about the molecular epidemiology of EB in Middle East populations. In the present study, we assessed 55 EB families for pathogenic sequence alterations in the 10 genes known to be associated with EB. Our results show unique EB subtype distribution and patterns of inheritance in our cohort. We also failed to detect recurrent mutations frequently encountered in Europe and the US, and did not consistently observe genotype-phenotype correlations formerly established in Western populations. Thus, the molecular epidemiology of EB in the Middle East is significantly different from that previously delineated in Europe and the US. Our data raise the possibility that similar differences may also be found in other genetically heterogeneous groups of disorders, and indicate the need for population-specific diagnostic and management approaches.

Congenital recessive ichthyoses represent a vast and markedly heterogeneous group of diseases that have been mapped to at least seven distinct chromosomal loci. In this study, we ascertained two consanguineous families presenting with congenital ichthyosis. Using homozygosity mapping, we identified a 6.5 cM homozygous region on 12p11.2-q13 shared by all affected individuals. Multipoint logarithm of odds ratio (LOD) score analysis placed the new locus between markers D12S345 and D12S390 with a maximum LOD score of 4.79 at marker CH12SSR13. This region harbors PPHLN1, encoding periphilin 1, a protein involved in the cornification process. No deleterious mutations were identified within the coding region of this gene, suggesting the existence of another gene associated with epidermal differentiation on 12p11.2-q13.

During the last years, a growing number of inherited skin disorders have been recognized to be caused by abnormal function of desmosomal proteins. In the present study, we describe the first female individuals affected with the ectodermal dysplasia/skin fragility syndrome (MIM604536), a rare autosomal recessive disease due to mutations in the PKP1 gene encoding plakophilin 1, a critical component of desmosomal plaque. One patient was shown to carry a homozygous splice site mutation in intron 4. The second patient displayed a homozygous recurrent mutation affecting the acceptor splice site of intron 1. Both mutations were associated with intraepidermal separation, widening of intercellular spaces, and abnormal desmosome ultrastructure, and were found to result in the absence of immunoreactive plakophilin 1 in the epidermis of the affected individuals. These two cases emphasize the role of molecular genetics in the assessment of congenital blistering in newborns and illustrate the importance of proper desmosomal activity for normal epidermis development and function.

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by abnormal growth of scalp hair during infancy, and by the later occurrence of macular degeneration leading to blindness during the first to third decade of life. Hypotrichosis with juvenile macular dystrophy was recently shown to result from mutations in CDH3 encoding P-cadherin. In this study, we assessed 27 individuals, including nine patients, belonging to five families in an attempt to characterize further the CDH3 mutation spectrum and delineate possible phenotype-genotype correlations. Deleterious biallelic mutations, predicted to lead to the translation of a dysfunctional protein, were found in all affected individuals. Four of these mutations are novel. Affected individuals of two large separate apparently unrelated families of Arab Israeli origin were found to carry the same homozygous mis-sense mutation (R503H) in exon 11 of the CDH3 gene. This mutation, which alters a Ca2+-binding site in the fourth extracellular domain of P-cadherin, was previously described in a third unrelated Arab Israeli family. Using haplotype analysis for a series of polymorphic markers encompassing the CDH3 gene, we obtained evidence suggesting a founder effect for R503H in the Arab Israeli population. We also compared the dermatologic and ophthalmologic features of 22 hypotrichosis with juvenile macular dystrophy patients with known recessive mutations in CDH3. Whereas hair paucity and macular degeneration were found in all patients, we noticed significant interfamilial and intrafamilial differences in hair morphology, associated skin findings as well as severity and age of onset of visual disability. Altogether, our results obtained in a series of families of various ethnic origins firmly establish mutations in CDH3 as the proximal cause of hypotrichosis with juvenile macular dystrophy and demonstrate genetic homogeneity as well as phenotypic heterogeneity in this disorder.

The cytoskeleton of epithelial cells is formed by heteropolymeric keratin proteins characterized by a central alpha-helical rod flanked by nonhelical head and tail domains of variable sequence. Most mutations described in 18 distinct keratins disrupt highly conserved regions at the boundaries of the rod, which have been recognized as zones of overlap during keratin alignment and assembly into intermediate filaments. We recently reported the first mutation located in a keratin tail domain (V2) in ichthyosis hystrix Curth-Macklin. In this study, we report two novel frameshift mutations that are predicted to alter the tail of keratin 1 or keratin 5, leading to an atypical form of epidermolytic hyperkeratosis and a mild form of epidermolysis bullosa simplex, respectively. Mutation analysis of the patient with epidermolytic hyperkeratosis revealed a de novo heterozygous nucleotide insertion (1752insG) in exon 9 of KRT1, predicted to result in an aberrant 69 residue keratin 1 tail. In the patient with mild epidermolysis bullosa simplex, we identified a single nucleotide deletion (1635delG) in exon 9 of KRT5 leading to frameshift and translation of an abnormal V2 domain, 35 amino acids longer than the native keratin 5 tail. Our results, together with previous observations, establish the existence of a subgroup of keratin disorders due to frameshift mutations altering the keratin tail domains that are characterized by phenotypic heterogeneity.

Sodium hyaluronate, or hyaluronic acid (HA), is a glucosaminoglucan used in pharmaceuticals in ophthalmic surgery and for treatment of rheumatoid arthritis. The average molecular mass of the HA polymer used in these products is often in the range 1 x 10(6)-5 x 10(6). Size-exclusion chromatography has been used for analysis of molecular masses, including the distribution, up to about 3 x 10(6). In this work, an anionic exchange chromatography method is presented by which the peak molecular mass and an estimation of the distribution of the molecular masses of HA is possible in the range 0.1 x 10(6)-5 x 10(6).

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by early hair loss heralding severe degenerative changes of the retinal macula and culminating in blindness during the second to third decade of life. Recently, we identified a frameshift mutation in the CDH3 gene encoding P-cadherin as the proximal cause of hypotrichosis with juvenile macular dystrophy in four families. We report here another consanguineous family in which four members were diagnosed with hypotrichosis with juvenile macular dystrophy. Light and scanning electron microscopy revealed in all patients morphologic hair shaft abnormalities consistent with pili torti. Ocular fundus examination disclosed marked degeneration of the macular pigment epithelium. Electrophysiologic studies were diagnostic for severe retinal dysfunction. DNA sequence analysis of the entire coding sequence of CDH3 revealed in all affected individuals a homozygous missense mutation resulting in a single amino acid substitution at position 503 of P-cadherin sequence (R503H). The mutation completely segregated with the hypotrichosis with juvenile macular dystrophy phenotype in the family but was not detectable in 83 healthy, unrelated controls. The amino acid substitution affects a highly conserved residue and is predicted to alter a Ca2+ binding domain of P-cadherin. This is the first pathogenic missense mutation reported in CDH3 and the second mutation found to underlie hypotrichosis with juvenile macular dystrophy. Our data establish recessive mutations in CDH3 as the molecular cause of hypotrichosis with juvenile macular dystrophy and expand our understanding of the pathophysiology of this intriguing disorder.

Congenital atrichias represent a large and heterogeneous group of inherited hair disorders. In this report, we describe a patient affected with alopecia universalis congenita (MIM 203655). Sequence analysis revealed a G to A transition at cDNA position 3034 of the hairless hr gene present in a homozygous state in the patient and in a heterozygous state in the patient's mother, and absent in the patient's sister. The mutation is predicted to result in the substitution of an asparagine residue for an aspartate amino acid (D1012N) at a position previously shown in the rat to affect hairless binding to thyroid hormone receptor. This study presents the first evidence in humans for the functional importance of the hairless thyroid receptor interacting domain 2.

Hypersensitivity syndrome is defined as a drug-induced complex of symptoms consisting of fever, rash, and internal organ involvement. The hypersensitivity syndrome is well recognized as being caused by anticonvulsants. Olanzapine is an atypical antipsychotic agent whose side effects include sedation, weight gain, and increased creatinine kinase and transaminase levels. To date, there have been no reports of hypersensitivity syndrome related to this drug. A 34-year-old man developed a severe generalized pruritic skin eruption, fever, eosinophilia, and toxic hepatitis 60 days after ingestion of olanzapine. After termination of olanzapine treatment, the fever resolved, the skin rash was reduced, eosinophil count was reduced to normal, and the transaminase levels were markedly reduced. Clinical features and the results of skin and liver biopsies indicated that the patient developed hypersensitivity syndrome caused by olanzapine.

Atrichia with papular lesions is a rare autosomal recessive form of alopecia characterized by hair loss soon after birth and the development during childhood of a diffuse papular rash. We have previously shown that this disorder results from a deleterious mutation in the human hairless gene, a gene also involved in the pathogenesis of a related but clinically distinct form of congenital alopecia, termed alopecia universalis congenita. In this report, we describe a novel nonsense mutation in exon 4 of the human hairless gene in a consanguineous kindred affected with atrichia with papular lesions. This report provides additional evidence for phenotypic heterogeneity among inherited atrichias and for an association between the papular rash of atrichia with papular lesions and nonsense mutations in the human hairless gene.

This article will present a new soft tissue cephalometric analysis tool. This analysis may be used by the orthodontist and surgeon as an aid in diagnosis and treatment planning. The analysis is a radiographic instrument that was developed directly from the philosophy expressed in Arnett and Bergman "Facial keys to orthodontic diagnosis and treatment planning, Parts I and II" (Am J Orthop Dentofacial Orthod 1993; 103:299-312 and 395-411). The novelty of this approach, as with the "Facial Keys" articles, is an emphasis on soft tissue facial measurement.

A set of nonionic cellulose ethers with varying hydrophobicity and molecular weight has been investigated by principal component analysis (PCA). Several experimental variables such as dynamic surface tension, diffusion coefficient, microviscosity as monitored by a fluorescence probe technique, and intrinsic viscosity are included in the analysis. The experimental variables and observations (polymer fractions) are analyzed in models with good predictive capacities. The apparent equilibrium surface tension correlates to the cloud point and to the critical aggregation concentration in the presence of surfactant. The microviscosity is shown to be a predictive parameter for the degree of hydrophobic substitution. The irreversible process of dynamic surface tension is dependent on the diffusion coefficient but to an even larger degree on the polymer concentration, which is well illustrated by the PCA models.

Introduction: Although recognition of insulin sensitivity as a risk factor for cardiovascular disease is growing, a deeper understanding of its role is impeded by the cost and complexity of currently available measures. This report evaluates previously described alternative indices of insulin sensitivity with the goal of identifying a reliable, but logistically simpler, alternative., Methods: Data from 1460 participants in the Insulin Resistance Atherosclerosis Study (IRAS) were used to assess the proportion of the relationship between a recognized measure of insulin sensitivity (Bergman's SI) and cardiovascular risk factors that is contained in each of nine alternative measures., Results: A number of the alternative indices contained a substantial proportion of the information available in Bergman's SI. The Galvin's index and the homeostasis model were most promising. However, there remained a significant amount of the information in Bergman's SI that was not contained in any of the alternative indices., Discussion: There are simpler alternative indices of insulin sensitivity for use in epidemiological studies, but each alternative is associated with some loss of information. It may be possible that this loss can be overcome with an increased sample size; however, using the alternative indices may also confound the assessment of insulin sensitivity with other underlying factors (i.e., hyperinsulinemia). The alternative indices are not recommended for the clinical assessment of insulin sensitivity for an individual patient or subject.

The effect of herbivory by bank vole (Clethrionomys glareolus) and moose (Alces alces) in relation to litterfall in a boreal forest is analysed. The main purpose is to estimate the relative importance of these processes for the transfer of caesium-137 to soil. Biomasses of litterfall and food consumption were selected from different forest biotopes. The analysis of the input and output of caesium-137 in the vole and moose populations is based on mass balance calculations for caesium-137 in steady state conditions. From this assessment, herbivory appears to be within an order of magnitude of litterfall. With due regard to the lower caesium level in litterfall than in living plant tissue, transfer of radioactive caesium by herbivory is seen to be even higher in comparison to that by litterfall, than apparent from the corresponding transfer of organic matter. In addition, the availability of caesium-137 from animal excrements is expected to be high and fast, which further emphasises the relative importance of herbivory and feed-back from vegetation to soil.

Adult xanthogranulomatosis is an uncommon disorder in which dermal macrophages accumulate cholesterol intracellularly despite normal plasma cholesterol levels. In an attempt to elucidate an underlying biochemical abnormality in this disorder, we studied the rates of 125I-labeled low-density lipoprotein degradation, and intracellular cholesterol synthesis, in human monocyte-derived macrophages of three patients with adult xanthogranulomatosis. In all three patients, the rates of cellular 125I-low-density lipoprotein degradation and of cholesterol synthesis were 22-37% and 14-84% higher than those of the respective normal controls (p < 0.01). These findings suggest that in MDM of adult xanthogranulomatosis patients, the uptake and degradation of low-density lipoprotein-derived cholesterol and intracellular cholesterol biosynthesis are enhanced. Because dermal macrophages are derived from blood monocytes, it is possible that such an enhancement might play a role in the accumulation of cholesteryl esters in the macrophages that form the xanthogranulomatosis lesions.

The present study was undertaken to compare the frequency of chromatid-type aberrations in Chinese hamster cells with previous results on accumulation of unrepaired DNA-strand breaks after incorporation of 3H-TdR or 125IUdR into DNA. A linear-quadratic function was fitted by the weighted-least-square method to the data on yield of chromatid aberrations at different dpm values. Based on a significant linear response at low doses, RBE for 125I in relation to 3H was calculated for (i) chromatid breaks (17 +/- 6), (ii) the sum of isochromatid breaks and chromatid exchanges (21 +/- 9), and (iii) the total number of chromatid aberrations (18 +/- 5). Analogously, the RBE for accumulation of DNA-strand breaks was determined (13 +/- 6). Our results are consistent with the assumption that chromosomal aberrations mainly originate from unrepaired DNA-strand breaks.

In the course of an ongoing screening of larger mushrooms for the occurrence of chemical mutagens, 33 out of 48 species tested exhibited a significant direct mutagenic activity in the Salmonella/microsome assay (Sterner et al., 1982). (No mutagens requiring metabolic activation were indicated.) These findings are of some concern, since mushrooms are used extensively as food in many areas, and there are strong indications that carcinogens in food are of considerable importance in cancer aetiology (Sugimura, 1979). A recent communication by Knuutinen and von Wright (1982) on the mutagenicity of 4 Lactarius species collected in Finland prompts us to report our own results from mutagenicity tests with commercially preserved (pickled) Lactarius necator.

The role of lavage fluid volume in recovery of cyclic antidepressant with gastric lavage was determined in 13 patients treated for moderate to severe cyclic antidepressant intoxication. An orogastric tube was placed, gastric contents aspirated, and gastric lavage performed with 60 to 180 mL aliquots of tap water or 0.9% NaCl for irrigation. A volume of 12.8 +/- 4.4 liters of lavage fluid was instilled, and 97.6 +/- 6.9% of this volume was recovered. The recovered aspirate and lavage fluid were inspected for the presence of particulate matter and saved in 4 to 5 liter collections. Determination of cyclic antidepressant and metabolite concentrations was performed using gas chromatography-mass spectrometry, and the amount of cyclic antidepressant recovered was calculated. The mean total amount recovered was 110 mg and ranged from 2.4 mg to 342 mg. Of the total amount recovered, 88% +/- 13% was recovered in the first 4 to 5 liters of lavage fluid. An estimate of the dose ingested was available in 7 patients, with 8.7% (0.4% to 21.7%) of the estimated dose recovered by lavage. There were no cases of significant drug recovery in clear lavage fluid. We conclude that if gastric lavage is undertaken in cyclic antidepressant intoxications, it should utilize 5 liters initially and then continue only if particulate matter is seen.

Specimens of large fungi (mushrooms) were screened for mutagenic activity by the Salmonella/microsome assay, with strains TA98, TA2637 and TA100. Our of 48 species tested, 37 exhibited a significant but for the most part weak activity. The activity observed in the presence of S9 mix was typically between 0 and 50% of that without, and in no case was the activity increased in the presence of microsomal enzymes. Six metabolites reported to occur in some of the species included in this investigation were also tested. Significant mutagenic activity was found with isovelleral (5) from Lactarius sp., agaritine (3) from Agaricus bisporus and related sp. and beta-nitraminoalanine (7) from Agaricus silvaticus. Isovelleral may be a major mutagen in some of the sharp-tasting and mutagenic Russulaceae sp. A. bisporus (cultivated specimen) was weakly mutagenic toward all three strains of S. typhimurium, used, and agaritine was weakly active toward TA2637 alone. This implies that this fungus might contain other mutagenic material as well. beta-Nitraminoalanine was not found in the particular collection of A. silvaticus tested here. The mutagenicity observed for the fungus in this work may therefore be due to other metabolites. Even though many species found to be mutagenic are used as food, it seems premature to make specific recommendations about eventual health risks. Further information is needed about the chemistry and toxicology of the active compounds as well as about the effects of various methods used in preparing mushrooms for food.

Fifty-nine patients in septic shock were observed for the development of the adult respiratory distress syndrome (ARDS) prior to and after receiving either 30 mg/kg methylprednisolone sodium succinate, 6 mg/kg dexamethasone sodium phosphate or no steroid. Serum levels of C3, C4 and Factor B allowed classification of 42 patients by activation of complement pathways. Despite a trend toward patients with severe septic shock who activate the alternative pathway being protected from the development of ARDS, complement pathway determination did not allow prediction of the development of ARDS and steroid pretreatment did not influence complement levels or prevent ARDS.