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Biomedical subjects

R Fischel

Publications and source records attributed to R Fischel.

At least 19 recordsLinked to original sources
PubMed2003

Microinvasive resectional sympathectomy using the harmonic scalpel. A more effective procedure with fewer side effects for treating essential hyperhidrosis of the hands, face or axillae.

Compensatory sweating remains one of the most unpredictable and debilitating complications of sympathectomy for hyperhidrosis. There appears to be a significant difference in compensatory sweating rates seen between the different techniques utilized to treat hyperhidrosis. Resectional techniques have historically resulted in excellent symptom relief with relatively low levels of severe post-op compensatory sweating. The advent of video-assisted approaches to the treatment of hyperhidrosis has led to other procedures including ablation/cautery, cutting and clipping of the nerve all of which report compensatory sweating rates between 70 and 100%. We have developed a minimally invasive video-assisted approach to sympathetic nerve resection. We studied 486 patients with severe essential hyperhidrosis affecting the hands, feet, axillae and face in variable combinations, who underwent bilateral resection of T2 and T3 for hand, facial or head sweating. 100% relief of sweating was noted in all cases. For axillary sweating the addition of T4 resection has resulted in complete relief of axillary hyperhidrosis symptoms. In this patient population our overall compensatory sweating rate has been approximately 18% with significant compensatory sweating occurring in less than 2% of patients.

Adaptation, Physiological↗
PubMed2001

Lupus anti-DNA autoantibodies cross-react with a glomerular structural protein: a case for tissue injury by molecular mimicry.

Anti-DNA autoantibodies are the hallmark of human and murine systemic lupus erythematosus (SLE), an autoimmune rheumatic disease of unknown etiology. Some of these antibodies are believed to be pathogenic for kidney tissue and to initiate immune glomerulonephritis. However, the mechanisms by which anti-DNA antibodies participate in tissue injury remain controversial. We have studied the in vivo pathogenicity of anti-DNA monoclonal antibodies in immune deficient mice, using a panel of murine B cell hybridomas. No consistent genetic or immunochemical differences were found between pathogenic and non-pathogenic anti-DNA antibodies. However, the two antibody populations differed in their cross-reaction with the acidic actin-binding protein, alpha-actinin, that is known to play a major role in the structural integrity of glomerular filtration components. These results suggest that kidney dysfunction in SLE may be facilitated by protein-nucleic acid antigenic mimicry.

Actinin↗
PubMed1999

Lung function after bilateral lower lobe lung volume reduction surgery for alpha1-antitrypsin emphysema.

This study explores the mechanism(s) of airflow limitation following lung volume reduction surgery (LVRS) in patients with emphysema due to homozygous alpha1-antitrypsin (AT) deficiency. Bilateral targeted lower lobe stapled LVRS using video thoracoscopy was performed in six patients (five males) aged 61+/-9 yrs (mean+/-SD) with alpha1-AT emphysema. Two patients received only a 6-month follow-up. However, four patients, at 22, 24, 27 and 36 months post-LVRS, noted relief from dyspnoea and increased walk tolerance. At 27+/-6 months (mean+/-SD) post-LVRS, their forced expiratory volume in one second improved only from 30+/-2% of the predicted value (mean+/-SEM) before surgery to 33+/-1% pred after surgery. Yet, total lung capacity (TLC) decreased from 151+/-13 to 127+/-10% pred; diffusing capacity increased from 35+/-9 to 59+/-9% pred; and vital capacity increased from 68+/-10 to 88+/-5% pred. In three patients, static lung elastic recoil at TLC increased from 1.1+/-0.15 to 1.2+/-0.10 kPa. Using flow/pressure curves, the mechanism for expiratory airflow limitation pre-LVRS and the improvement noted post-LVRS could be primarily accounted for by the initial loss and subsequent increase in lung elastic recoil. Bilateral lung volume reduction surgery provides modest physiologic improvement for 2-3 yrs in patients with alpha1-antitrypsin emphysema due to increases in lung elastic recoil.

Dyspnea↗
PubMed1999

Lung function 4 years after lung volume reduction surgery for emphysema.

STUDY OBJECTIVES: Current data for patients > 2 years after lung volume reduction surgery (LVRS) for emphysema is limited. This prospective study evaluates pre-LVRS baseline data and provides long-term results in 26 patients. INTERVENTION: Bilateral targeted upper lobe stapled LVRS using video thoracoscopy was performed in 26 symptomatic patients (18 men) aged 67 +/- 6 years (mean +/- SD) with severe and heterogenous distribution of emphysema on lung CT. Lung function studies were measured before and up to 4 years after LVRS unless death intervened. RESULTS: No patients were lost to follow-up. Baseline FEV(1) was 0.7 +/- 0.2 L, 29 +/- 10% predicted; FVC, 2.1 +/- 0.6 L, 58 +/- 14% predicted (mean +/- SD); maximum oxygen consumption, 5.7 +/- 3.8 mL/min/kg (normal, > 18 mL/min/kg); dyspneic class > or = 3 (able to walk < or = 100 yards) and oxygen dependence part- or full-time in 18 patients. Following LVRS, mortality due to respiratory failure at 1, 2, 3, and 4 years was 4%, 19%, 31%, and 46%, respectively. At 1, 2, 3, and 4 years after LVRS, an increase above baseline for FEV(1) > 200 mL and/or FVC > 400 mL was noted in 73%, 46%, 35%, and 27% of patients, respectively; a decrease in dyspnea grade > or = 1 in 88%, 69%, 46%, and 27% of patients, respectively; and elimination of oxygen dependence in 78%, 50%, 33%, and 22% of patients, respectively. The mechanism for expiratory airflow improvement was accounted for by the increase in both lung elastic recoil and small airway intraluminal caliber and reduction in hyperinflation. Only FVC and vital capacity (VC) of all preoperative lung function studies could identify the 9 patients with significant physiologic improvement at > 3 years after LVRS, respectively, from 10 patients who responded < or = 2 years and died within 4 years (p < 0.01). CONCLUSIONS: Bilateral LVRS provides clinical and physiologic improvement for > 3 years in 9 of 26 patients with emphysema primarily due to both increased lung elastic recoil and small airway caliber and decreased hyperinflation. The 9 patients had VC and FVC greater at baseline (p < 0.01) when compared to 10 short-term responders who died < 4 years after LVRS.

Aged↗
PubMed1998

Serial lung function and elastic recoil 2 years after lung volume reduction surgery for emphysema.

STUDY OBJECTIVE: To evaluate serial lung function studies, including elastic recoil, in patients with severe emphysema who undergo lung volume reduction surgery (LVRS). To determine mechanism(s) responsible for changes in airflow limitation. METHODS: We studied 12 (10 male) patients aged 68+/-9 years (mean+/-SD) 6 to 12 months prior to and at 6-month intervals for 2 years after thoracoscopic bilateral LVRS for emphysema. RESULTS: At 2 years post-LVRS, relief of dyspnea remained improved in 10 of 12 patients, and partial or full-time oxygen dependency was eliminated in 2 of 7 patients. There was significant reduction in total lung capacity (TLC) compared with pre-LVRS baseline, 7.8+/-0.6 L (mean+/-SEM) (133+/-5% predicted) vs 8.6+/-0.6 L (144+/-5% predicted) (p=0.003); functional residual capacity, 5.6+/-0.5 L (157+/-9% predicted) vs 6.7+/-0.5 L (185+/-10% predicted) (p=0.001); and residual volume, 4.9+/-0.5 L (210+/-16% predicted) vs 6.0+/-0.5 L (260+/-13% predicted) (p=0.000). Increases were noted in FEV1, 0.88+/-0.08 L (37+/-6% predicted) vs 0.72+/-0.05 L (29+/-3% predicted) (p=0.02); diffusing capacity, 8.5+/-1.0 mL/min/mm Hg (43+/-3% predicted) vs 4.2+/-0.7 mL/min/mm Hg (18+/-3% predicted) (p=0.001); static lung elastic recoil pressure at TLC (Pstat), 13.7+/-0.5 cm H2O vs 11.3+/-0.6 cm H2O (p=0.008); and maximum oxygen consumption, 8.7+/-0.8 mL/min/kg vs 6.9+/-1.5 mL/min/kg (p=0.03). Increase in FEV1 correlated with the increase in TLC Pstat/TLC (r=0.75, p=0.03), but not with any baseline parameter. CONCLUSION: Two years post-LVRS, there is variable clinical and physiologic improvement that does not correlate with any baseline parameter. Increased lung elastic recoil appears to be the primary mechanism for improved airflow limitation.

Aged↗
PubMed1996

Contribution of lung and chest wall mechanics following emphysema resection.

OBJECTIVE: To determine the contributions of (1) chest wall (Pcw) and (2) lung elastic recoil pressure (PL) to (3) total elastic recoil pressure exerted by the respiratory system (Prs) in 18 patients (12 men) aged 66 +/- 6 years (mean +/- 1 SD) with severe emphysema who underwent video-assisted thoracoscopic bilateral lung volume reduction surgery under paralyzed (vecuronium) general anesthesia (isoflurane). DESIGN: We measured preoperative and 6-week postoperative lung function studies, and intraoperative inspiratory lung conductance (GL), PL, Pcw, and Prs (cm H2O) at end-expiratory lung volume (EELV), EELV plus 0.60 +/- 0.0 L, and EELV plus 1.15 +/- 0.0 L. All values are mean +/- SEM. RESULTS: Preoperative vs postoperative FVC was 1.9 +/- 0.1 L vs 2.3 +/- 0.1 L (p = 0.03); FEV1 was 0.6 +/- 0.1 L vs 0.9 +/- 0.1 L (p < 0.02); total lung capacity was 7.4 +/- 0.4 L vs 5.9 +/- 0.3 L (p < 0.001); functional residual capacity was 5.7 +/- 0.4 L vs 4.4 +/- 0.2 L (p = 0.001). At EELV preoperative vs postoperative, PL was 0.0 +/- 0.3 vs 1.1 +/- 0.05 (p = 0.04), Pcw was 5.0 +/- 0.7 vs 2.4 +/- 0.9 (p = 0.02), and Prs was 5.0 +/- 0.8 vs 3.5 +/- 0.7 (p = 0.08). AT EELV plus 0.60 L, PL was 3.2 +/- 0.6 vs 6.1 +/- 0.9 (p < 0.001), Pcw was 8.8 +/- 0.8 vs 7.0 +/- 0.9 (p = 0.12), and Prs was 12.0 +/- 0.8 vs 13.1 +/- 0.7 (p = 0.80). At EELV plus 1.15 L, PL was 6.8 +/- 0.9 vs 10.3 +/- 1.1 (p < 0.001), Pcw was 13.5 +/- 1.0 vs 11.2 +/- 1.2 (p = 0.12), and Prs was 20 +/- 1.2 vs 21.5 +/- 1.0 p = 0.93). AT EELV plus 0.06 L, GL was 0.09 +/- 0.00 L/S/cm H2O vs 0.16 +/- 0.01 (p < 0.01). At EELV plus 1.15 L, GL was 0.12 +/- 0.01 vs 0.21 +/- 0.03 (p < 0.05) with similar preoperative vs postoperative GL/PL slopes. CONCLUSION: The increase in PL and decrease in Pcw following LVRS for emphysema may be responsible for the increase in spirometry and airway conductance.

Aged↗
PubMed1996

Lung volume reduction surgery for emphysema.

There has been dramatic resurgence of interest in surgical treatment of emphysema, particularly "lung volume reduction" procedures. Recent studies have demonstrated improvements in pulmonary function, lung mechanics, exercise tolerance, and quality of life in selected patients following volume reduction procedures. However, considerable uncertainty remains regarding overall benefit, optimal patient selection, operative techniques, and duration of response. This summarizes current approaches to lung volume reduction surgery, available clinical outcome information, selection criteria, and physiologic mechanisms of response, and discusses the potential role for surgical volume reduction in treatment of emphysema. Recent data appear to support the efficacy of bilateral staple lung volume reduction surgery in patients with severe symptomatic heterogeneously distributed emphysema. Further studies will be needed to determine relative value of different operative techniques and benefit in patients with other clinical presentations.

Algorithms↗
PubMed1996

Lung function 12 months following emphysema resection.

OBJECTIVE: To investigate the mechanism of airflow limitation before and 6 and 12 months after targeted emphysematous resection in 10 male patients aged 67 +/- 8 years (mean +/- SD) with very severe COPD undergoing bilateral thoracoscopic stapling techniques. DESIGN: Lung function, including static lung elastic recoil, was measured 2 weeks before and 6 and 12 months after surgery. RESULTS: Twelve months after surgery, there was a significant (p < 0.001) reduction in total lung capacity (TLC), 9.5 +/- 0.3 L (mean +/- SEM) to 8.5 +/- 0.3 L, functional residual capacity, and residual volume. Airway conductance and FEV1, 0.71 +/- 0.1 L (mean +/- SEM) to 0.95 +/- 0.1 L, improved significantly (p < 0.01). Lung elastic recoil increased markedly at TLC from 11.7 +/- 0.7 cm H2O (mean +/- SEM) to 15.0 +/- 1.0 cm H2O (p < 0.01) as did maximum expiratory airflow in every patient. However, when compared with data obtained in each patient at 6 months, lung volumes are significantly increased, and expiratory airflow and lung elastic recoil pressures are significantly reduced (p < or = 0.05). Analysis of maximum expiratory flow-static elastic recoil pressure curve indicates conductance of the S airway segment (Gs) increased from 0.20 +/- 0.03 L/s/cm H2O (mean +/- SEM) to 0.28 +/- 0.04 L/s/cm H2O (p < 0.02), and critical transmural pressure in the collapsible segment (Ptm') decreased from 3.2 +/- 0.2 cm H2O (mean +/- SEM) to 2.5 +/- 0.2 cm H2O (p < 0.01). CONCLUSION: The improvement in maximal expiratory airflow can be attributed primarily to increased lung elastic recoil and its secondary effect on enlarging airway diameter causing increased airway conductance, increased Gs, and decreased Ptm'. The improvement in lung function and elastic recoil peaks at 6 months.

Aged↗
PubMed1993

Anti-SSA/Ro and anti-SSB/La antibodies in serum and saliva of patients with Sjogren's syndrome.

Autoantibodies to SSA/Ro and SSB/La antigens may have a pathogenic role in photosensitive skin disease and congenital complete heart block. Since salivary glands are the major target organ in Sjogren's syndrome (SS) we wondered whether these autoantibodies are present in saliva and may be involved in the sicca syndrome. Whole saliva and serum were collected from 15 patients with SS. Elisa analysis disclosed that 8 of the patients had anti-SSA/Ro antibodies, while 6 of them also had anti-SSB/La antibodies. Studies of immunoglobulin classes showed that the sera contained mainly IgG and IgM anti-SSA/Ro or SSB/La antibodies. One serum also contained IgA antibodies. Analysis of the saliva showed that in all positive samples IgG and IgA classes were present, while none of them contained IgM. Elisa and immunoblot analysis of sera and saliva from SLE patients without the sicca syndrome disclosed that both fluids contained anti-Sm antibodies. These findings suggest that the presence of anti-SSA/Ro and anti-SSB/La antibodies in saliva is not a unique phenomenon, characterizing the sicca syndrome. Therefore, their role in the pathogenicity of the Sjogren's syndrome has to be elucidated.

Antibodies, Antinuclear↗
PubMed1992

Structure and binding properties of a monoclonal anti-idiotypic autoantibody to anti-DNA with epibody activity.

We report the isolation and characterization of a mouse autoanti-idiotypic mAb (D7.4 IgG2a), which is directed against a major public Id (A52 IgG2b) in the murine and human autoimmune response to DNA. The natural anti-Id mAb has been produced in the course of the SLE-like disease in a female NZB/NZW F1 mouse and showed a dual specificity (epibody activity) for the public Id (A52) and for the autoantigen (DNA). The two binding activities were shown to reside in the Fab portion of the epibody and were highly specific for their respective Ag. A complete nucleotide sequence analysis of the D7.4 H and L chain V-region genes combined with computer comparisons to available Ig sequences may suggest a charge interaction between the H chain CDR3 segments of the Id and anti-Id antibodies. The D7.4 epibody may be a component of the self-binding, idiotypically connected network of natural antibodies. Alternatively, it could be elicited against the potentially pathogenic, DNA-containing immune complexes in order to facilitate their removal from the circulation of diseased individuals.

Amino Acid Sequence↗
PubMed1991

Recurrent utilization of genetic elements in V regions of antinucleic acid antibodies from autoimmune mice.

Two IgG anti-DNA and two IgG anti-RNA autoantibodies derived from lupus prone NZB/NZW F1 mice have been analyzed for their Ag fine specificities and for their H and L chain V-region sequences. A remarkable similarity of VH gene sequences with previously sequenced antinucleic acid autoantibodies (Eilat, D., D. M. Webster and A. R. Rees. J. Immunol. 141:1745, 1988) was noted. This finding indicates that a small number of unique VH genes is involved in this autoimmune response and that the sequences of these genes are correlated with the different specificities for the autoantigen. The VK sequences appeared, by computer search, to be selected nonrandomly, but their use was not restricted to autoantibodies. An additional striking feature was evident in the construction of the D region elements, giving rise to CDR3 peptides that can interact with DNA and RNA. These constructs probably include D-D fusion products, which are relatively rare in Ig rearrangements.

Amino Acid Sequence↗
PubMed1990

Cellular immunity in species with variable rejection of vascularized grafts.

We studied the in vitro and in vivo cellular response in three distinctly different xenograft models, using C57BL/6 mice as responders and Lewis rats (LR), Golden Syrian hamsters (GSH), and Strain 2 guinea pigs (GP) as stimulators. Previous work has shown that cardiac grafts from rats, hamsters, and guinea pigs are rejected by C57BL/6 mice in 7 days, 4 days, and 10 min., respectively. In xenogeneic mixed lymphocyte culture, response was in general greatest to GSH splenocytes: stimulation index (S.I.) = 11.4 +/- 3.6 followed by the response to LR cells, S.I. = 3.5 +/- .09, which was less than that of an allogeneic control C57BL/6 anti-DBA, S.I. = 8.4 +/- 1.7. GP stimulator splenocytes produced inhibition of response (S.I. = 0.23 +/- .07) with all counts being below baseline and remaining low despite addition of IL-1, IL-2, or both. In fact, these cells were inhibitory to other allo or xeno mixed lymphocyte cultures in a dose-dependent manner. Cytotoxicity studies revealed maximal killing of ConA blasts in the allogeneic control followed by killing of GSH blasts and LR blasts and no killing of GP blasts. There was also a moderate degree of nonspecific killing between allo and xeno systems. In vivo analysis of cell-mediated cytotoxicity was done using a sponge matrix allograft model. The sponge was injected with donor cells and implanted into C57BL/6 mice. The response to donor cells was tested using cells accumulating in the sponge. There was maximal response to GSH cells greater than DBA greater than LR greater than GP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

IgG rheumatoid factor in purified IgG fractions and whole sera from patients with rheumatoid arthritis.

There are inherent technical difficulties in measuring IgG rheumatoid factor (IgG-RF) in the serum of patients with rheumatoid arthritis (RA). These arise from measuring a reaction between two IgG molecules and the interference of IgM-RF in the reaction. We compared the prevalence of IgG-RF in whole sera and purified IgG fractions from 58 RA patients (43 of whom were latex or sheep cell agglutination positive). Methods of purification were: ammonium sulphate precipitation and DEAE cellulose or protein A-Sepharose chromatography. IgG-RF was measured by two methods: (1) radioimmunoassay and ELISA with a monoclonal myeloma IgG (IgG4,K) as the antigen and radiolabelled rabbit anti-human IgG (previously absorbed on a column with IgG4,K) as the second antibody; (2) ELISA using rabbit IgG as the antigen and a peroxidase conjugated goat anti-human IgG as the second antibody. When whole sera were assayed, 18 (31%) contained IgG-RF. In contrast, only three of the IgG fractions (5%) were positive for IgG-RF by all methods, while the remainder were uniformly negative. These results suggest that IgG-RF determination in whole sera does not accurately reflect IgG-RF activity.

Antigens↗
PubMed1989

Successful human double-lung transplantation after five and one-half hours of preservation.

Successful clinical double-lung transplantation after 5 1/2 hours of pulmonary ischemia is reported. Static hypothermic preservation with a high-volume, high flow rate-modified Collin's solution pulmonary artery flush was used. Excellent early and late pulmonary function demonstrates the efficacy of the technique that is described in detail. Lung transplantation remains limited by the lack of reliable methods of long-term storage of donor organs, but refinement of current techniques may soon allow its wider application.

Adult↗
PubMed1986

Evaluation of the cross-reaction between anti-DNA and anti-cardiolipin antibodies in SLE and experimental animals.

The cross-reaction between anti-DNA and anti-cardiolipin IgG antibodies and its relation to the standard test for syphilis was studied with sera and monoclonal antibodies derived from human patients and mice with systemic lupus erythematosus (SLE). Syphilitic sera of humans and rabbits infected with the spirochete Treponema pallidum were also tested in this study. In addition, rabbits were immunized with ssDNA and cardiolipin and the cross-reactions of the induced antibodies were studied in two different assay systems. The results of these experiments suggest: that the anti-DNA and anti-cardiolipin IgG autoantibodies in SLE sera constitute separate antibody populations and, therefore, cardiolipin cannot play a role in the induction of immune response to DNA in SLE; that in immunized experimental animals there is a significant level of cross-reaction between anti-DNA and anti-cardiolipin-the detection of this cross-reaction depends on highly amplified solid phase assay systems which measure low affinity antibodies and that there is no correlation between the activity of syphilitic sera in the serologic test for syphilis and their binding to pure cardiolipin-this implies that cardiolipin may not be the dominant ingredient in this test as previously proposed.

Animals↗