The tibial cut in total knee arthroplasty influences the varus alignment, the femoral roll-back and the tibiofemoral rotation in patients with constitutional varus.

PURPOSE: Different alignment types for a better outcome after TKA were described. However, it is not clear how kinematic alignment influences knee joint kinematic. The purpose of this study was to analyze whether adapted tibial cuts in constitutional varus knees affect knee joint kinematics regarding femoral roll-back, varus/valgus angle, and femorotibial rotation. METHODS: Seven cadaveric knees with constitutional varus alignment were examined in the native state and after implantation of a cruciate retaining (CR)-TKA with 0°, 3° and 6° tibia cuts using an established knee joint simulator. The effects of varus alignment on femorotibial rollback and rotation was determined. In addition, the native knee joint and different tibial cuts in CR-TKA were compared with Student's t test. RESULTS: Total knee replacement with a 3° and 6° varus tibia cut had the greatest varus deviation to the native knee (mean 1.6° ± 0.09°, respectively); while, knees with a 0° (mean 0.2° ± 0.01°) tibia cut were most similar to the constitutional varus knee joint. The femoral roll-back in the medial compartment was increased in the native knee (5.7-12.5 mm). A 6° varus cut had a restricted translation in the medial compartment (2-3.2 mm). In the lateral compartment, the extensive translation was observed with a 0° varus cut, followed by 3° and 6° and the native knee. All cuts showed significantly different mean values. Only the cuts at 3° and at 6° in the medial compartment and the cuts at 0° and at 3° in the lateral compartment did not differ significantly. In respect to tibiofemoral rotation, 0° and 3° varus cuts across all loads had the least difference to the native knee (3.4°), with a 0° varus cut showing a higher absolute internal rotation of the tibia than the native knee. Changes in knee kinematics of the tibiofemoral rotation showed significantly different mean values. CONCLUSION: The potentially improved outcome parameters in TKA with adapted tibia cuts in constitutional varus knees cannot be completely explained by the changes to knee kinematics. Mechanical alignment seems to result in more balanced load distribution and kinematics more closely resembling the native knee. From a kinematic point of view, it is not recommended to place the tibia in more than 3° of varus. LEVEL OF EVIDENCE: Biomechanical study.

Demyelinating Charcot-Marie-Tooth neuropathy associated with FBLN5 mutations.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1 (CMT1) is a group of autosomal dominantly inherited demyelinating sensorimotor neuropathies. Symptoms usually start in the first to second decade and include distal muscle weakness and wasting, sensory disturbances and foot deformities. The most frequent cause is a duplication of PMP22 whilst point mutations in PMP22 and other genes are rare causes. Recently, FBLN5 mutations have been reported in CMT1 families. METHODS: Individuals with FBLN5-associated CMT1 were compiled from clinical and research genetic testing laboratories. Clinical data were extracted from medical records or obtained during patients' visits at our centres or primary care sites. RESULTS: Nineteen CMT1 families containing 38 carriers of three different FBLN5 missense variants were identified and a mutational hotspot at c.1117C>T (p.Arg373Cys) was confirmed. Compared to patients with the common PMP22 duplication, individuals with FBLN5 variants had a later age of diagnosis (third to fifth decade) and less severely reduced motor median nerve conduction velocities (around 31 m/s). The most frequent clinical presentations were prominent sensory disturbances and painful sensations, often as initial symptom and pronounced in the upper limbs, contrasting with rather mild to moderate motor deficits. CONCLUSIONS: Our study confirms the relevance of FBLN5 mutations in CMT1. It is proposed to include FBLN5 in the genetic work-up of individuals suspected with CMT1, particularly when diagnosis is established beyond the first and second decade and comparably moderate motor deficits contrast with early and marked sensory involvement. FBLN5-associated CMT1 has a recognizable clinical phenotype and should be referred to as CMT1H according to the current classification scheme.

The tibial cut influences the patellofemoral knee kinematics and pressure distribution in total knee arthroplasty with constitutional varus alignment.

PURPOSE: The current literature suggests that kinematic total knee arthroplasty (kTKA) may be associated with better outcome scores in patients with constitutional varus alignment. The underlying patellofemoral kinematic changes (patella tilting and patella tracking) and patellofemoral pressure distribution have not yet been described. The present study compared the effects of different tibial cuts, as used in kTKA, on patellofemoral knee kinematics and the pressure distribution, in addition to comparisons with the natural constitutional varus knee. METHODS: Seven cadaveric knee joints with constitutional varus alignment were examined in the native state and after 0°, 3°, or 6° tibial cut cruciate-retaining (CR)-TKA using an established knee joint simulator. The effects on patella rotation/patella tilting, patellofemoral pressure, and patellofemoral length ratios (= patella tracking) were determined. In addition, the natural knee joint and different tibial cuts in CR-TKA were compared (Student's t test). RESULTS: In the patellofemoral joint, 6° CR-TKA was associated with the greatest similarity with the natural constitutional varus knee. By contrast, knees subjected to 0° CR-TKA exhibited the largest deviations of patellar kinematics. The smallest difference compared with the natural knee joint concerning patella tilting was found for 6° CR-TKA (mean 0.4°, p < 0.001), and the largest difference was noted for 0° CR-TKA (mean 1.7°, p < 0.001). Concerning patellofemoral pressure, 6° CR-TKA resulted in outcomes most similar to the natural knee joint, featuring a mean difference of 3 MPa. The largest difference from the natural knee joint was identified for 0° CR-TKA, with an average difference of 8.1 MPa (p < 0.001; total mean 17.7 MPa). Meanwhile, 3° and 6° CR-TKA induced medialization of the patella, with the latter inducing the largest medialization value of 4.5 mm at 90° flexion. CONCLUSIONS: The improved outcome parameters in kTKA described in the literature could be attributable to the similar kinematics of the patellofemoral joint relative to the normal state. The current study confirmed the similar kinematics between the native constitutional varus knee joint and knee joints subjected to 3° or 6° CR-TKA (patellofemoral rotation/patella tilting and patella pressure). Conversely, there was pronounced medialization of the patella following 6° CR-TKA. Patella pressure and patella tilting are described in the literature as possible causes of anterior knee pain after TKA, whereas medialization of the patella, which is also influenced by other causes, might play a subordinate role. LEVEL OF EVIDENCE: V, Biomechanical study.

Proteome analysis identifies L1CAM/CD171 and DPP4/CD26 as novel markers of human skin mast cells.

BACKGROUND: The function of skin mast cells has been well documented in IgE-mediated allergic reactions, whereas other mast cell functions are poorly defined. This study aimed at identifying novel mast cell proteins by proteome analysis of primary human skin mast cells. METHODS: The proteome of skin mast cells was compared to other cell types and analyzed using bioinformatics. The expression and function of two proteins hitherto not described in skin mast cells was investigated in isolated mast cells as well as in mast cells in situ. RESULTS: Within the mast cell proteome, we identified 49 highly expressed proteins previously not described in mast cells; 21 of these proteins were found to be selectively expressed in mast cells. Two proteins, the neural cell adhesion molecule L1 and dipeptidyl peptidase 4, were further studied. L1 was found to be highly expressed in mast cells in normal, psoriasis, and mastocytosis skin. Dipeptidyl peptidase 4 was found to be expressed in mast cells in normal, psoriasis, and mastocytosis skin as well as in bone marrow mast cells in patients with systemic mastocytosis. In normal skin, mast cells were identified as a major source of dipeptidyl peptidase 4 and we also found that skin mast cells and fibroblasts secrete an active form of this enzyme. CONCLUSIONS: In a systematic proteomics approach we identified two novel mast cell proteins potentially relevant to skin homeostasis: neural cell adhesion molecule L1 and dipeptidyl peptidase 4.

Advocating individual-based profiles of elite athletes to capture the multifactorial nature of elite sports performance.

Elite athletes are high-performance outliers within their specific sports. Even though science seeks to understand the nature of expertise and elite performance, much knowledge remains compartmentalized within subdisciplines. Despite this multidimensionality being acknowledged, an interdisciplinary approach to understanding elite athletes is still rare. This paper synthesizes insights across scientific domains in order to describe the population and individual characteristics of elite athletes. We analyzed diagnostic data from approximately 300 German squad athletes across eight different sports (e.g., gymnastics, volleyball, ice hockey, 3 × 3 basketball etc., agefemale = 18.95 ± 4.84 years, agemale = 19.32 ± 4.19 years) with expertise values ranging from 2 (low expertise) to 16 (high expertise). Data covered muscular strength, lower-body dynamics, muscle-power genetics, blood micronutrients, basic cognitive function, mental health, social support, and training conditions. Results of logistic regressions identified basic cognitive function (B = 0.89) and well-balanced blood micronutrients (B = 1.22) as critical factors distinguishing elite athletes. Additionally, multiple linear regressions suggested that lower-body dynamics (ß = 0.72) is related to increasing expertise values. We examined interactions between determinants of elite performance, and found that social support is positively associated with mental health and training conditions, whereas muscular strength correlates with lower-body dynamics. Focusing on top elite athletes in contrast to semi-elite athletes, we found higher within-group similarities in basic cognitive function and blood micronutrients. Findings indicate the need for a systemic, individualized, and comprehensive model using individual-based profiles.

Meningoencephaloradiculomyelitis after tick-borne encephalitis virus infection: a case series.

BACKGROUND: Tick-borne encephalitis (TBE) is caused by a RNA-virus and is in about 50% of cases characterized by a biphasic clinical course in adults. Different clinical syndromes have been described, including meningitis, meningoencephalitis, meningoencephalomyelitis and meningoencephaloradiculomyelitis. The latter seems to be the most disabling and severe form of TBE virus infection. METHODS: Here we report five cases with meningoencephaloradiculomyelitis. Only in three patients a tick prick was remembered. RESULTS: Only two patients could be weaned successfully from assisted ventilation; only one patient was able to return to self-dependent life without nursing support. The youngest patient in this case series showed the most favourable outcome. CONCLUSIONS: Polyradiculopathy and/or myelopathy as verified by electrophysiological examination within 4 weeks from symptom onset were indicative of a more severe disease course and a greater likelihood of moderate to serious sequelae even after long-term rehabilitation. Older age at symptom onset seems to be associated with a less favourable outcome. Because of frequent long-term hospitalization with immobilization and invasive ventilation, secondary complications, such as ventilation associated pulmonary infections and decubiti, must be avoided.

T cell senescence and contraction of T cell repertoire diversity in patients with chronic obstructive pulmonary disease.

Pathogenetic mechanisms leading to chronic obstructive pulmonary disease (COPD) remain poorly understood. Because clonogenic T cells (CD4(+)CD28(null)) were shown to be increased in autoimmune diseases we hypothesized that CD4(+)CD28(null) T cells play a role in COPD. Here we describe that enhanced presence of CD4(+)CD28(null) cells is associated with impaired lung function. Sixty-four patients and controls were included. T cell phenotype was analysed using flow cytometry. Enzyme-linked immunosorbent assays were utilized to determine cytokines. Statistical evaluations were performed using non-parametric group comparisons and correlations. A logistic regression model was used to determine predictive values of CD4(+)CD28(null) in the diagnosis of COPD. Populations of CD4(+) T cells lacking surface co-stimulatory CD28 were enlarged significantly in evaluated patients when compared with controls. Natural killer (NK)-like T cell receptors (CD94, 158) and intracellular perforin, granzyme B were increased in CD4(+)CD28(null) cells. Cytokine production after triggering of peripheral blood mononuclear cells (PBMCs) was elevated in patients at early disease stages. Receiver operating characteristic curve plotting revealed that presence of CD4(+)CD28(null) T cells has a diagnostic value. These CD4(+)CD28(null) T cells show increased expression of NK-like T cell receptors (CD94, 158) and intracellular perforin and granzyme B. Furthermore, triggering of PBMCs obtained from patients with mild COPD led to increased interferon-gamma and tumour necrosis factor-alpha production in vitro compared with controls. Our finding of increased CD4(+)CD28(null) T cells in COPD indicates that chronic antigen exposure, e.g. through contents of smoke, leads to loss of CD28 and up-regulation of NK cell receptors expression on T cells in susceptible patients.

Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardium.

BACKGROUND: Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium. METHODS: Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to quantify interleukin-8 (IL-8), vascular endothelial growth factor, matrix metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model. Immunohistological analysis was performed to detect inflammatory and pro-angiogenic cells within 72 h post-infarction. Functional data and determination of infarction size were quantified by echocardiography and Elastica van Gieson staining. RESULTS: The IA-PBMC attenuated immune reactivity and resulted in secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial progenitor cells within 72 h as compared to control (medium alone, viable-PBMC). Echocardiography showed a significant reduction in infarction size and improvement in post AMI remodelling as evidenced by an attenuated loss of ejection fraction. CONCLUSION: These data indicate that infusion of IA-PBMC cell suspension in experimental AMI circumvented inflammation, caused preferential homing of regenerative EPC and replaced infarcted myocardium.

Alpha-Gal specific IgG immune response after implantation of bioprostheses.

BACKGROUND: We have previously shown that the alpha-Gal (Galalpha1.3-Galbeta1-4GlcNAc-R) epitope is a relevant xenoantigen present on bioprostheses utilized in cardiac surgery and elicits an alpha-Gal specific IgM immune response. We sought to investigate whether that immune response continues after valve implantation. MATERIALS AND METHODS: We collected plasma samples from patients who underwent bioprosthesis implantation (n = 19) or mechanical valve replacement (n = 8), respectively, prior to, at 10 days and at 3 months after cardiac surgery. ELISA was utilized to quantify alpha-Gal specific IgG and IgG subclasses. 3 bioprosthetic tissue samples were obtained from patients who had to undergo re-operation within 1 week (n = 1) or at 12-15 months (n = 2) after the initial operation. We utilized confocal laser scanning microscopy (CLSM) to detect the presence of alpha-Gal epitopes (IB4) and cell nuclei (DAPI). RESULTS: alpha-Gal specific IgG was significantly increased 3 months after implantation of bioprostheses compared to preoperative values (p < 0.001) and was significantly higher than alpha-Gal specific IgG levels of the control group (p < 0.05). IgG3 was the major subclass directed against alpha-Gal (p < 0.05, pre- vs. postoperative values). In CLSM analysis we demonstrated that bioprostheses explanted 1 week after implantation contained IB4/DAPI positive cells within the collagen matrix. In contrast, in patients who underwent reoperation after 12 months, porcine tissue showed a complete lack of IB4/DAPI. CONCLUSION: Our results indicate that the implantation of bioprostheses elicits a specific humoral immune response against alpha-Gal bearing cells compared to controls within 3 months after cardiac surgery. The complete absence of IB4/DAPI positive structures 12 months after implantation indicates a specific degradation of alpha-Gal bearing cells through previous exposure to the human blood circuit.

Myocardial lipofuscin-laden lysosomes contain the apoptosis marker caspase-cleaved cytokeratin-18.

BACKGROUND: Acute coronary syndrome is related to increased circulatory concentration of soluble apoptosis specific caspase-cleaved cytokeratin-18 (ccCK-18). Potential cardiac sources of this intermediate filament derivative have not been investigated to date. MATERIALS AND METHODS: Paraffin embedded tissue of normal myocardium, and chronically damaged samples of ischaemic, congestive and hypertrophic cardiomyopathy were analysed by histology and by CK-8, CK-18, ccCK-18 immunohistochemistry (each group, n = 15). Antibody specificity of the ccCK-18 antibody M30 was checked by immunoblotting on lysed myocardium and enriched myocardial lysosomes. RESULTS: ccCK-18 and CK-18 but not CK-8 were present in all forms of cardiomyopathy, most prominently in ischaemic cardiomyopathy while only traces were detectable immunohistochemically in normal myocardium. Weak CK-18 and strong ccCK-18 staining co-localized to lysosomes with cardiac age pigment lipofuscin. Weak staining of CK-18 was detected in the cytoplasm of coronary endothelia. CONCLUSION: Our study reveals that cardiac lipofuscin-laden lysosomes contain ccCK-18, a marker of apoptosis and its precursor CK-18. This ccCK-18 pool might contribute to increased systemic levels of ccCK-18 in acute coronary syndrome thus monitoring myocardial damage.

Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro.

BACKGROUND: Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). OBJECTIVES: To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation. METHODS: The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32). CONCLUSIONS: Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.

Features of haptic and tactile feedback in TORS-a comparison of available surgical systems.

Sustained interest and an increase of possible indications endorse the role of robot-assisted surgery of the head and neck region. However, broad clinical application is impeded by substantial extra cost, time exposure and a supposed deficit of haptic and tactile feedback. The role of haptic feedback has barely been examined in this context, and literature provides only limited objective validation. This point of criticism applies to all commercially available systems. We created an experimental setup to evaluate, quantify and compare the performance of surgical systems. The daVinci system (Intuitive Surgical), the Flex system (Medrobotics) and standard rigid instruments (23 cm laryngoscopic grasper, Karl Storz) were compared with the human hand by head and neck surgeons (n = 15), performing a variety of surgical tasks. Specific samples with different rigidity were sorted with all devices, and the resulting orders were analyzed by permutation analysis, indicating differences in precision and accuracy of haptic and tactile feedback. The human hand was superior in all trials, acting as reference modality. The flexible instruments of the Flex system performed better than the electro-mechanically decoupled instruments of the daVinci system for the majority of measures recorded, suggesting a benefit in terms of haptic and tactile feedback in this context. While not all aspects of haptic and tactile feedback were accessible, this first objective comparison endorses the inferiority of robot-assisted surgery in terms of haptic and tactile feedback, compared to the human sense or standard surgical tools. Furthermore, the immediate force transmission of the Flex system seems to be superior to the electro-mechanical transformation of the daVinci system, indicating an advantage in terms of haptic and tactile feedback in immediate comparison. This study is providing a basis for further experiments and the development of robotic surgery towards an implementation in clinical routine.

Persistent spatial structuring of coastal ocean acidification in the California Current System.

The near-term progression of ocean acidification (OA) is projected to bring about sharp changes in the chemistry of coastal upwelling ecosystems. The distribution of OA exposure across these early-impact systems, however, is highly uncertain and limits our understanding of whether and how spatial management actions can be deployed to ameliorate future impacts. Through a novel coastal OA observing network, we have uncovered a remarkably persistent spatial mosaic in the penetration of acidified waters into ecologically-important nearshore habitats across 1,000 km of the California Current Large Marine Ecosystem. In the most severe exposure hotspots, suboptimal conditions for calcifying organisms encompassed up to 56% of the summer season, and were accompanied by some of the lowest and most variable pH environments known for the surface ocean. Persistent refuge areas were also found, highlighting new opportunities for local adaptation to address the global challenge of OA in productive coastal systems.

Objective and subjective evaluation of donor-site morbidity after nipple sharing for nipple areola reconstruction.

Nipple reconstruction is of importance in achieving the best possible aesthetic outcome after breast reconstruction. Nipple sharing is a common technique; this study focused on the potential morbidity at the donor nipple. Between 2008 and 2012, 26 patients underwent nipple sharing at our institution. The donor nipple was examined before and after the procedure (mean follow-up of 21 months). Sensitivity, projection, diameter, and patient satisfaction were evaluated. The sensitivity in the donor nipple decreased, albeit insignificantly, from 1.2 g/mm2 (0.8-1.6) to 1.8 g/mm2 (0.8-4.8) (p=0.054, n=26). The projection due to graft removal decreased from 8.0 mm (6.8-10.0) to 4.5 mm (4.0-5.0) (p=0.001). Of the patients, 88% were "very satisfied" or "somewhat satisfied" with the sensitivity and 89% with the symmetry between the donor and reconstructed nipple. At least 60% of the patients were "very satisfied" with all aesthetic outcome parameters (projection, appearance, naturalness, color, and shape). All patients would agree to undergo this procedure again, if necessary. Nipple sharing was associated with minimal morbidity at the donor nipple. The postoperative projection was adequate. Regardless of whether simultaneous mastopexy was performed, the loss of sensitivity was minimal and presumably imperceptible to the patient. By using no sutures after graft removal and letting the donor nipple heal spontaneously, scarring was minimized and the natural appearance and good sensitivity of the donor nipple were preserved.

Port-a-Cath extravasation of vesicant cytotoxics: surgical options for a rare complication of cancer chemotherapy.

BACKGROUND: Although implantation of a central venous device such as a Port-a-Cath was initially considered safe, extravasation rates up to 4.7% have been reported. Therefore, the objective of this study was to propose a structured procedure for the management of extravasation of a cytotoxic treatment. METHODS: A total of eight patients were evaluated after port extravasation of epirubicin (n = 3), platinum compounds (n = 3), paclitaxel (n = 1), or trabectedin (n = 1) into the subcutaneous space. Immediate explantation of the port was performed in combination with a "Subcutaneous Wash-Out Procedure" (SWOP). When removal of the port was delayed, débridement and flap coverage were performed as necessary. Epirubicin concentrations present in the samples obtained during surgical intervention were subsequently analysed using high-performance liquid chromatography (HPLC). Patients were followed for at least six months and were examined for sequelae such as pain, induration, redness, and limited movement. RESULTS: All three patients whose extravasation event was detected during chemotherapy administration benefited from SWOP with acceptable side effects (e.g., erythema). The analysis of epirubicin concentrations demonstrated the active removal of relevant amounts of the compound by wound rinsing. In contrast, late detection of extravasation led to major débridement and flap coverage in four out of five patients. A high body mass index (BMI) value was associated with all of the patients that experienced port extravasation. CONCLUSION: Depending on when Port-a-Cath extravasations into subcutaneous tissue are detected, different treatments are appropriate. When extravasation is detected early, the SWOP was found to be beneficial.

Independent regulation of beta 1- and beta 2-adrenoceptors.

1 The down-regulation of beta-adrenoceptors has been postulated as a biochemical marker of antidepressant efficacy. Here we demonstrate that chronic treatment with desipramine down-regulates beta 1-adrenoceptors in rat cerebral cortex and that beta-adrenoceptor subtypes can be independently regulated by treatment with different beta-adrenoceptor agonists. 2 Desipramine, (+/-)-clenbuterol, prenalterol, corwin (20 mg kg-1 daily) and corwin (10 mg kg-1 daily) were administered to male, Sprague-Dawley rats, over eight days, by means of osmotic Alzet pumps placed subcutaneously and removed 24 h before analysis. Control rats received vehicle only. The beta 1- and beta 2-adrenoceptor populations were measured in cerebral cortex by a modified (-)-[125I]-pindolol receptor binding assay. 3 The conventional antidepressant, desipramine, preferentially down-regulated beta 1-adrenoceptors whereas the non-selective beta-adrenoceptor agonist (+/-)-clenbuterol preferentially down-regulated beta 2-adrenoceptors. The beta 1-selective partial agonist, prenalterol, up-regulated beta 1-adrenoceptors perhaps acting more as an antagonist than as an agonist. Finally, neither dose of corwin had any significant effect on beta-adrenoceptor number.

A low incidence of histiocytic sarcomatosis associated with infection of chickens with the HPRS-103 strain of subgroup J avian leukosis virus.

Ten cases of histiocytic proliferative lesions in meat-type chickens associated in low incidence with infection by subgroup J avian leukosis virus (ALV) are described. Six were field cases in adult chickens from naturally infected flocks and four were from younger birds from transmission experiments with HPRS-103 ALV or the related acutely transforming ALV strains 17 and 879. The lesions were observed mostly in the spleen and in some cases in other organs. Microscopically, the lesions were comprised mainly of pleomorphic histiocyte-like cells admixed with variable numbers of lymphoid cells. More detailed studies were carried out on two birds at 4 and 7 wk of age following infection with HPRS-103 at 1 day of age. These birds had multiple small nodular lesions in the spleen, liver, and kidney that appeared similar cytologically to the more extensive lesions in older birds. Monoclonal antibodies specific for various lymphoid and nonlymphoid accessory cells were used in immunohistochemical studies to identify a predominance of cells of monocyte/macrophage lineage, and CD4- and CD8-positive lymphocytes, in the splenic nodules. Ultrastructural studies also revealed a similar mixed population of cells. Expression of ALV group-specific antigen, and gag and ALV-J env RNA, was not a marked feature of the histiocytic lesions. The proliferative histiocytic lesion is designated a histiocytic sarcomatosis.

Porphyria cutanea tarda in a patient with hairy cell leukemia.

The case of porphyria cutanea tarda occurring in a patient treated for hairy cell leukemia is presented. Porphyria cutanea tarda has recently been associated with a variety of hematologic disorders and the acquired immunodeficiency syndrome. Potential mechanisms explaining this association are discussed.

Temporary ectropion due to topical fluorouracil.

A patient with multiple actinic keratoses was treated with the standard regimen of 5 percent fluorouracil cream. The patient noted bilateral ectropion within two weeks of receiving therapy. The ectropion completely resolved with discontinuation of therapy. This is the first reported case of transient ectropion associated with 5-fluorouracil therapy.