Eccentric/concentric training of ankle evertor and dorsiflexors in recreational athletes: muscle latency and strength.

The aim of this study was to investigate the effects of a combined eccentric-concentric exercise program of the ankle evertors and dorsiflexors on the latency time of the peroneus longus and tibialis anterior muscles. Twenty-four healthy male recreational athletes were admitted to this study and were randomly assigned to either the exercise group (n = 12) or the control group (n = 12). Subjects in the exercise group performed an isokinetic exercise program of the ankle evertors and dorsiflexors in a combined eccentric-concentric mode for 3 days per week for 6 weeks. Before and after the exercise program, muscle reaction times of the peroneus longus and tibialis anterior muscles to sudden supinating maneuvers on a tilting platform, and isokinetic strength of the ankle joint musculature were evaluated. The peroneus longus and tibialis anterior reaction times showed significant (P < 0.01-0.05) reductions following six weeks of intervention in the exercise group. Additionally, eccentric peak torques for the ankle evertor and dorsiflexors represented significant (P < 0.05) increases in the exercise group compared with the control group. The results of this study suggest that it is possible to reduce peroneal and anterior tibial reaction times following a six week eccentric/concentric isokinetic training program in healthy ankles.

Analysis of T cell signaling by class I MHC molecules: the cytoplasmic domain is not required for signal transduction.

The structural requirements for signal transduction by class I major histocompatibility complex (MHC) molecules were examined. Native or mutant HLA-A2 or HLA-B27 constructs lacking most of their cytoplasmic domains were co-transfected with pSV2neo into Jurkat cells. Transfection of either native or mutant constructs resulted in a comparable expression of the gene products. Stimulation of transfectants expressing either native or truncated A2 or B27 molecules with specific mAb evoked an increase in [Ca2+]i upon crosslinking. Moreover, crosslinking native or truncated A2 or B27 induced IL-2 production upon co-stimulation with phorbol myristate acetate. These results confirm that crosslinking class I MHC molecules transduces an activation signal to human T cells. Effective signaling was observed when all but four of the intracytoplasmic residues were deleted, indicating that signal transduction does not require this portion of the molecule.

Colonoscopic screening of an average-risk population for colorectal neoplasia.

BACKGROUND AND STUDY AIMS: The role of screening colonoscopy in an asymptomatic, average-risk population remains to be determined. Moreover, the value of screening colonoscopy in individuals older than 75 years and for right-sided lesions has recently been questioned. The aims were to assess: (i) the risk of colorectal neoplasia in a large consecutively screened asymptomatic average-risk population, aged 40-85 years; (ii) whether colonoscopy is better than sigmoidoscopy for primary screening; and (iii) the prevalence of right-sided lesions at different ages. PATIENTS AND METHODS: This prospective study, analyzed data from 1563 consecutive, asymptomatic, average-risk individuals, aged 40-85 years, who underwent screening colonoscopy. RESULTS: Overall, neoplastic lesions were detected in 262 individuals (17% of the study population), of whom 75 had advanced lesions (5% of population) and nine had colorectal cancers (CRC) (0.6% of population). The prevalence of all lesions increased with age, with the highest percentages in the > 75 age group (26.5% with neoplastic and 6 % with advanced lesions). Higher age was also associated with relatively more right-sided lesions. In particular the prevalence of proximal neoplasia, without concurrent distal neoplasia, increased from 5% in those < 50 years to 24% in those > 75 years. Those with distal lesions had a higher overall risk for proximal lesions (odds ratio [OR] 3.2); nevertheless flexible sigmoidoscopy alone would have missed up to 40% of all lesions and up to 3.5% of advanced neoplastic lesions in this patient subgroup. CONCLUSIONS: Screening colonoscopy in asymptomatic, average-risk individuals is mandatory, as noteworthy numbers of advanced colorectal neoplasias have been detected in all age groups, especially in those aged > 75. Most importantly, many of the detected lesions were proximal and would not be revealed by sigmoidoscopy alone.

Validation of the 2017 revision of the WHO chronic myelomonocytic leukemia categories.

The 2017 revision of the World Health Organization (WHO) classification includes substantial changes to the subclassification of chronic myelomonocytic leukemia (CMML): (1) a 3-tiered blast-based scheme including a novel "CMML-0" category replacing a 2-tiered system in place since 2001 and (2) 2 CMML subtypes, myelodysplastic (MDS-CMML) and myeloproliferative (MP-CMML), based on a white blood cell count cutoff of 13 × 109/L. The clinical utility of this subclassification scheme, particularly the expansion of blast-based subgroups, has not been validated. In this study, a large single-institution CMML patient cohort (n = 629) was used to assess the prognostic impact of the newly proposed categories. Patients were risk stratified according to the CMML-specific Prognostic Scoring System (CPSS) and the MD Anderson Prognostic Scoring System. MP-CMML patients had significantly shorter overall survival (OS; P < .0001; hazard ratio: 0.53, 95% confidence interval: 0.42-0.65) and median duration to acute myeloid leukemia (AML) transformation (P < .0001; 15.2 vs 22.0 months) compared with MDS-CMML patients. The CMML-0 group included 36.4% patients with higher risk CPSS categories and 11.2% of patients with high-risk cytogenetics. Among treatment-naïve patients (n = 499), there was a marginal difference in OS between the CMML-0 and CMML-12017 subgroups (P = .0552). The WHO 2017 blast-based categories were not associated with AML-free survival. Incorporation of the WHO 2017 blast-based subgroups in a modified CPSS scheme had a neutral effect and did not improve its prognostic strength. Our data support the inclusion of MP-CMML and MDS-CMML subtypes in the WHO 2017 revision. Although of some utility in MP-CMML, the 3-tiered blast-based system is not well supported in this study.

The effect of local application of insulin-like growth factor for prevention of inner-ear damage caused by electrode trauma.

BACKGROUND: Electrode insertion during cochlear implantation causes cochlear damage and apoptosis. Insulin-like growth factor applied locally was investigated in 21 rats. METHODS: In the sham group, an intracochlear dummy electrode was inserted through the round window. In the control group, after the same insertion procedure, saline-soaked porcine skin gelatine was placed on the round window. In the study group, insulin-like growth factor 1 soaked gelatine was placed on the round window. Auditory brainstem response thresholds were measured and histopathological examination was performed. RESULTS: In the study group, at 2-4 kHz, one rat had deterioration, one showed improvement and the rest had stable thresholds 14 days after intervention. At 6 kHz, four rats showed improvement and the rest remained stable. At 8 kHz, four showed improvement, one had deterioration and two remained stable. In the other groups, hearing loss deteriorated in about half of the rats and remained stable in the rest. The mean post-operative 6 kHz threshold was significantly lower than that immediately after the intervention in the study group, contrary to the other groups. The study group had significantly better mean histopathological grading than the other groups. CONCLUSION: Local insulin-like growth factor 1 application may protect hearing after cochlear implantation.

Disseminated mycobacterial disease caused by Mycobacterium szulgai.

Disseminated mycobacterial disease due to Mycobacterium szulgai occurred in a previously healthy young man. The clinical picture included fever, mediastinal and generalized lymphadenopathy, hemoptysis, and skin lesions but was dominated by progressive multifocal osteomyelitis. Immunological studies revealed a decrease in T-lymphocyte reaction to mitogens, but this was tested late in the course of the disease and may have been secondary. In spite of repeated surgical drainage and treatment with multiple antituberculous drugs for a period of two years, new lesions continue to appear mainly in the bones. Mycobacterium szulgai was isolated from 28 bone specimens, as well as from skin lesions and sputum. To the best of our knowledge, this is the first report of disseminated disease due to this organism.

Structural analysis of class I MHC molecules: the cytoplasmic domain is not required for cytoskeletal association, aggregation and internalization.

The role of the cytoplasmic domain in a variety of the functional activities of class I MHC molecules has not been documented. To address this question, Jurkat cells were transfected with genes for either native class I MHC molecules or constructs in which all but four cytoplasmic amino acids were deleted. Antibody-induced aggregation and internalization of class I MHC molecules were examined by flow cytometry, and cytoskeletal association was determined by analysing the detergent-resistant fraction of FITC-labeled mAb to class I molecules. The results indicate that the truncated class I MHC molecules are comparable to native class I MHC molecules in the ability to move in the plane of the membrane and aggregate, to associate with the cytoskeleton and to undergo mAb-induced internalization at 37 degrees C. Thus, the cytoplasmic domain of class I MHC molecules is not required for these functional activities.

Systemic vasculitis presenting as a tumorlike lesion. Four case reports and an analysis of 79 reported cases.

Systemic vasculitis might present as a tumorlike lesion that initially could misdirect the correct diagnosis and the appropriate medical treatment. The aim of the present study is to summarize all reported cases of tumorlike presentation in systemic vasculitides, in order to have comprehensive data on the characteristics of this unusual phenomenon. We report 4 cases of systemic vasculitis presenting as a tumorlike lesion. In addition, we performed a MEDLINE search of all English-language papers published from 1966 to 1999, looking for vasculitis presenting as tumorlike lesion. Details were included concerning vasculitis classification, specific characteristics, location of the "tumor," the presence or absence of systemic involvement, and whether surgery was performed before diagnosis. Seventy-nine cases of vasculitis presenting as a tumorlike lesion were found in the literature, in addition to the 4 new cases described. The average age of the reported cases was 50.5 +/- 15.8 years, and 51% were female. In 82% of the cases the "tumor" was associated with constitutional symptoms and elevated erythrocyte sedimentation rate (ESR). The most common vasculitis categories with tumorlike presentation were Wegener granulomatosis (WG; 28 cases) and giant cell arteritis (GCA; 17 cases). In almost half the patients, surgery was performed before diagnosis. All patients with GCA presented with either a breast or an ovarian tumor. The most common location of a tumorlike lesion was the breast (22%), followed by central nervous system lesions (16%). Other frequent locations were the ovary (10%), caused exclusively by GCA and polyarteritis nodosa (PAN), and the male genitourinary system, almost all caused by PAN. Including vasculitis in the differential diagnosis of a tumorlike lesion might lead to an earlier diagnosis and consequently to prompt and appropriate treatment, avoiding needless operations. Constitutional symptoms and elevated ESR should alert clinicians to the possible diagnosis of vasculitis rather than a tumor. The association of GCA with ovarian pseudotumor is distinct and has not been emphasized before. We therefore suggest that GCA should be included in the list of differential diagnosis of an ovarian or breast tumor in an elderly woman, particularly when systemic symptoms and parameters of inflammation are present.

Experimental autoimmune encephalomyelitis induced in B6.C-H-2bm12 mice by myelin oligodendrocyte glycoprotein: effect of MHC class II mutation on immunodominant epitope selection and fine epitope specificity of encephalitogenic T cells.

The effect of the bm12 mutation on susceptibility to MOG-induced EAE, TCR repertoire and fine epitope specificity of the encephalitogenic T-cells, was assessed. prMOG35-55 was encephalitogenic for H-2bm12 and H-2b mice. Despite only minor differences in TCRVbeta expression and fine epitope specificity, H-2bm12/ and H-2b/prMOG35-55-specific T-cells failed to recognize Ab/prMOG35-55 and Abm12/prMOG35-55, respectively. rhMOG-induced EAE was milder in H-2bm12 mice, possibly as a result of co-dominant responses to prMOG35-55 and to the non-encephalitogenic pMOG94-116, rather than a single dominant response to prMOG35-55 in H-2b mice.

Aspergillosis in systemic lupus erythematosus.

Infection is the major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although various fungi account for a substantial number of these lethal infections, aspergillosis, an important opportunistic infection in immunosuppressed patients, is described rarely. Only 23 cases have been reported in the English-language medical literature. Risk factors for acquiring aspergillosis in these patients were high grade disease activity, granulocytopenia, use of steroids and other immunosuppressive treatment and presence of bacterial infection. The diagnosis in most patients was delayed and they died. Here, we describe three SLE patients with invasive aspergillosis. Features of our patients' diseases were similar to those reported previously. Aspergillosis appeared while they had active SLE treated with high dose corticosteroids. In 2 patients the fungal infection was systemic and diagnosed post mortem. Both were leukopenic and had concurrent bacterial infection and one received amphotericin B prior to death. In the third, the infection was localized to a transplanted kidney and was cured by nephrectomy. Aspergillosis should be suspected in patients with active SLE, who are immunocompromised and sustain concomitant bacterial infections. The currently poor prognosis may be improved with more aggressive diagnostic investigation and treatment.

Pulmonary-renal syndrome in systemic sclerosis.

BACKGROUND AND OBJECTIVE: Renal failure, pulmonary hypertension, and interstitial lung disease are major causes of morbidity and mortality in systemic sclerosis (SSc). However, the concomitant occurrence of pulmonary hemorrhage associated with acute renal failure in SSc has been rarely described. The present study is the first analysis of pulmonary-renal syndrome in SSc. PATIENT AND METHODS: We present a 44-year-old woman with SSc who died of a fulminant course of acute renal failure associated with diffuse alveolar hemorrhage. We termed this uncommon and fatal complication of SSc scleroderma-pulmonary-renal syndrome (SPRS). A search of the English-written literature yielded reports of 10 additional similar cases. These patients, together with our present case, form the basis of the present analysis. RESULTS: The average age of the patients with SPRS was 46 years. The majority of the patients (80%) were women, and most had diffuse SSc. SPRS occurred an average of 6.4 years after disease onset and was associated with prior fibrosing alveolitis and/or D-penicillamine treatment. Interestingly, normotensive renal failure seems to characterize the scleroderma patients, because 9 of 11 (82%) had normal blood pressure. SPRS bears a poor prognosis: all of the 11 patients (100%) died within 12 months of admission. However, only 60% of the 5 patients for whom we have treatment data received corticosteroids. CONCLUSIONS: Pulmonary-renal syndrome is a rare but fatal complication of SSc. Because the treatment data are scarce and the prognosis is poor, aggressive treatment with pulse corticosteroids, cyclophosphamide, and possibly plasmapheresis is suggested.

Polyarteritis nodosa in patients with Familial Mediterranean Fever (FMF): a concomitant disease or a feature of FMF?

BACKGROUND: Familial Mediterranean Fever (FMF) is caused by mutations in the gene encoding pyrin and is characterized by self-limited, recurrent attacks of fever and serositis. Vasculitis has been increasingly reported in FMF. A study evaluating the prognosis in FMF and polyarteritis nodosa (PAN) patients has not been reported previously. OBJECTIVES: To determine the special characteristics and the prognosis of PAN in FMF patients. METHODS: A questionnaire was used for the present survey. The setting was 7 referral centers from Turkey and Israel. Seventeen patients who were diagnosed with FMF and who developed PAN were included. PAN was diagnosed in those who met the Chapel Hill consensus criteria for microscopic polyarteritis or classic PAN. The clinical features of these 17 patients and the outcomes of their vasculitis were analyzed. RESULTS: The age at diagnosis of PAN in these FMF patients ranged from 3.5 to 37 years. All patients had constitutional symptoms, elevated acute phase reactants, and myalgia at the time PAN was diagnosed. The diagnosis of PAN was confirmed by renal angiography in 8 patients, by renal biopsy in 6 patients, and by muscle and/or nodule biopsies in 6 patients. A number of patients had definite features of both classic PAN and microscopic polyarteritis. CONCLUSIONS: When compared with other PAN patients, those with FMF tended to have a younger age at PAN onset, more frequent perirenal hematomas, and an overall better prognosis. The cases with overlapping features of microscopic and classic PAN pose a problem for the current classification of vasculitis. We suggest that the clinical representation of PAN in FMF patients has certain characteristics and may be a feature of FMF per se.

High incidence of malignancies in patients with dermatomyositis and polymyositis: an 11-year analysis.

OBJECTIVES: Dermatomyositis and polymyositis (DM/PM) are associated with neoplasms. The aim of the present study is to compare our experience in Israel with other published data. METHODS: Thirty-five adult patients with DM/PM, admitted to Sheba Medical Center during the 11-year interval between 1984 and 1994, were studied for the prevalence and features of malignant diseases. Patients with DM/PM alone and with DM/PM and malignancy were identified by using the hospital computer system. The manifestations of DM/PM and features of the malignant diseases were abstracted from the patients' charts. The presence or absence of malignancy and the type of cancer were verified in the National Cancer Registry. RESULTS: There were 15 men and 20 women. The mean age at the onset of the disease was 53 +/- 18 years. A total of 15 had PM and 20 DM. Malignancies occurred in four patients with PM (27%) and in nine with DM (45%) a frequency 12.6 times higher than in the general population. In six patients, the malignancy and the DM/PM were diagnosed simultaneously; in four before and in three after the appearance of the DM/PM. Hematologic, gastrointestinal, breast, ovarian, and lung tumors, malignant melanoma, and metastatic carcinoma of unknown primary were found among our patients. Eight DM/PM patients with malignancy died during the study period of infection, pulmonary embolism, and tumor spread. CONCLUSIONS: Our study found that DM/PM is associated with high rates of malignancy and mortality.

Superantigens and experimental SLE induced by idiotypic dysregulation.

OBJECTIVE: The effects of the superantigens (SAgs) Staphylococcal Enterotoxin B (SEB), Toxic Shock Syndrome Toxin-1 (TSST-1) and Mycoplasma Arthritidis Mitogen (MAM) were examined on the induction and on the course of experimental SLE-like disease. METHODS: Immunization of BALB/c mice with human anti-DNA mAb (MIV-7) carrying the pathogenic idiotype 16/6 emulsified in complete Freund's adjuvant (CFA), followed by a boost of MIV-7/PBS 3 weeks later, generated an experimental SLE via an idiotypic dysregulation. RESULTS: After immunization with MIV-7/SAg, replacing the MIV-7 boost by SAg, and then injecting SAg 7 weeks after the regular induction of the SLE-like disease, the mice failed to produce anti-hIgM and dsDNA Ab up to 6 months after the induction. The mice immunized with MIV-7/CFA and boosted with the SAg had high titers of anti-hIgM but no detectable anti-dsDNA Ab. In both experimental groups low titers of anti-CL Abs developed in 25/40 (62%) and 30/38 (79%) of the mice respectively, including the control mice immunized with non-pathogenic human IgM/SAg or PBS/SAg. The mice immunized according to the "classical" protocol showed increased titers of anti-dsDNA Ab (22%) and anti-CL Ab (28%) during 10 weeks of observation. In contrast SEB, TSST-1 and MAM induced a 29%, 1% and 17% reduction in the anti-DNA titers and a 32%, 15% and 12% reduction in the anti-CL titers, respectively. CONCLUSIONS: These data suggest that the SAg tested here cannot replace the effect of CFA in the induction of the primary humoral response. The SAgs TSST-1, SEB and MAM did not induce the SLE-like disease following idiotypic modulation. Moreover, they may have had a suppressive effect on the idiotypic network in our model. The appearance of anti-CL Abs in almost all the experimental groups including the naive mice supports the possibility that microbial SAgs can induce the production of autoantibodies by different mechanisms. The SAgs TSST-1, SEB and MAM reduced autoantibody production in the serologically established idiotypic-induced experimental SLE-like murine model. This beneficial effect may indicate new directions for research on the management of SLE.

Rhabdomyolysis associated with clozapine treatment in a patient with decreased calcium-dependent potassium permeability of cell membranes.

A 21-year-old patient developed rhabdomyolysis during his nineteenth week of treatment with clozapine for drug-resistant schizophrenia. No risk factors for rhabdomyolysis were found, but the calcium-dependent potassium efflux, normally responsible for membrane hyperpolarization and muscle refractoriness, was severely decreased in the patient's red blood cells. Clozapine is speculated to cause rhabdomyolysis in patients with defective calcium-activated K+ channels.

Damping characteristics of teeth with periodontal breakdown: correlation of mobility meter values with bone and attachment loss.

The reaction of the periodontium to a defined percussive force applied in an orofacial direction can be evaluated by a mobility meter. The elastic and viscous characteristics of the periodontium are evaluated by the device from the contact time between tapping head and the tooth, and reported as a numeric value called the PTV. In this study, the relation between PTVs and bone loss (BL), clinical attachment level (CAL), probing depth, bleeding on probing, and plaque and gingival indices were evaluated in 35 patients with moderate to advanced periodontal disease. The effects of gender, smoking, and initial periodontal therapy on PTVs were also evaluated. Repeated measures analysis of variance was used to determine whether the relationship between PTVs with CAL and BL was dependent on tooth type. Stepwise multiple linear regression was used to test which of the clinical parameters and bone loss would produce the highest predictive value with PTVs. The effects of gender and smoking on PTVs were examined by analysis of covariance. The changes in clinical parameters and PTVs before and after treatment were evaluated by repeated analysis of variance. PTVs were found to give the highest predictive value with bone loss. However, the correlation was observed to be dependent on the location of the tooth in the jaw and the tooth type. Interproximal and midpoint clinical attachment level measurements showed that PTVs correlated more strongly with the overall support, rather than the support on the direction of the percussive movement. No pronounced differences of PTVs were noted between gender. PTVs of smokers were observed to be higher than non-smokers. There was no significant change of PTVs after the initial phase of periodontal therapy. This cross-sectional study shows that the mobility meter evaluation was primarily related to the amount of bone loss while being significantly affected by the location of the tooth in the jaw. Factors such as severity of gingival and sulcular inflammation, oral hygiene, and gender do not seem to have an effect on PTVs.

Polyarteritis nodosa: a report from Israel.

BACKGROUND: The clinical manifestations and outcome of all adult patients with polyarteritis nodosa (PAN), allocated during a 15-year period in the largest medical center in Israel, were examined. METHODS: A retrospective analysis of patients with PAN who fulfilled the American College of Rheumatology (ACR) 1990 Classification Criteria and were either biopsy- or angiography-proven. RESULTS: Nine patients were included in the report. The clinical and laboratory manifestations were similar to those in previous studies. All patients were treated with combinations of cyclophosphamide and corticosteroids. There were two (22%) deaths, 2 and 5 months after initiation of treatment in patients who probably had microscopic polyangiitis (MPA) rather than classical PAN. Considering the patients with a complete follow-up, 71% had a complete and long-term remission. Moreover, by exclusion of the two patients with probable MPA who died, all of the five patients with classical PAN were alive and well as of this writing. Two patients (22%) had a long history, since childhood, of familial Mediterranean fever (FMF). CONCLUSIONS: The clinical presentation and course of PAN in Israeli patients is comparable with reports elsewhere. However, a distinction should be made between PAN and MPA. The present report emphasizes the good long-term prognosis of patients with typical PAN who are treated adequately. In addition, a possible association of PAN with FMF in Israeli patients is suggested.

The benign long-term effect of cholesterol crystal synovial cysts.

Synovial effusions containing cholesterol crystals are uncommon. Most of the few reported cases have been found in patients with seropositive rheumatoid arthritis. In vitro studies, as well as an animal model, have suggested that cholesterol crystals could have a role in inflammation of the joints. In this report we present a case of seronegative arthritis, complicated by large carpal synovial cysts which contained numerous cholesterol crystals. The long-term presence of the cysts, without evidence of joint destruction, suggests that cholesterol crystal formation is probably a rare epiphenomenon, rather than a harbinger of inflammation.

Pleural effusion as a presenting manifestation of giant cell arteritis.

Pulmonary involvement is rare in giant cell arteritis (GCA). Only a few cases have been reported, manifested by interstitial infiltration, pulmonary nodules, pulmonary artery vasculitis, and granuloma formation. Moreover, only 3 previous cases of pleural effusion associated with GCA have been described. Herein we report a 67-year-old woman with biopsy-proven temporal arteritis, presented with prolonged fever, weight loss, cough and pleural effusion. ELISA test for the presence of anti- proteinase-3 antibodies was negative. The importance of the anti-neutrophil cytoplasmic-antibodies (ANCA) examination in the differential diagnosis from other vasculitides with pulmonary involvement is discussed.