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Biomedical subjects

M G Cohen

Publications and source records attributed to M G Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1992

Mortality in systemic lupus erythematosus: active disease is the most important factor.

Although systemic lupus erythematosus (SLE) no longer has the very poor prognosis that it had 50 years ago, there remains a significant mortality. We were able to determine the causes of death in 27 of the 29 patients with SLE who died over the period 1985 to 1989. This represents one and five year mortality of six and 24% respectively. In common with other studies, sepsis was a major factor, being implicated in the deaths of 37% of our patients. However, sepsis (i) occurred almost exclusively in patients with active SLE; (ii) often occurred after prolonged hospitalisation; and (iii) was a terminal event in otherwise fatal SLE in several patients. Overall, active disease was determined to be a cause of death in 67% of the patients. An unexpected observation was the finding that active cardiopulmonary disease accounted for 37% of deaths. Although late mortality from degenerative vascular disease is being increasingly reported with the modern prolonged SLE survivorship, it was identified in only one patient. We conclude that active disease remains the most important factor in mortality in SLE.

Adolescent↗
PubMed1992

Antibodies to histones in systemic lupus erythematosus: prevalence, specificity, and relationship to clinical and laboratory features.

Antibodies to histones (AHA) are commonly found in patients with systemic lupus erythematosus (SLE). However, the full profile of AHA and their clinical associations remains unclear. A total of 111 patients with SLE were studied, including 13 patients in whom multiple serum samples were available over several years. IgM, IgG, and IgA antibodies to total core histones, histone complexes, and individual histones were determined by highly sensitive enzyme linked immunosorbent assays (ELISAs). Antibodies to histones were detected in 74% of serum samples, though only at low levels in half of these. Antibodies to each of the individual histones (H1, H2A, H2B, H3, H4) occurred with similar frequencies except for IgG and IgA antibodies to H4, which were uncommon. In contrast, antibodies to the histone complexes H2A-H2B and H3-H4 were detected in only two serum samples and thus do not appear to be a feature of SLE. All three major isotypes of AHA were common and usually occurred with similar frequencies to one another for the various histone specificities. There were few clinical or laboratory associations with AHA; the strongest was between IgG antibodies to total core histones and antibodies to native DNA. Similarly, there was no association between the presence of AHA and disease activity. However, for the patients as a group and in one patient alone, periods of SLE disease activity were associated with higher levels of AHA. Although the profile of antibodies to individual histones varied with time, no profile was identified that corresponded with any specific disease manifestations. It is concluded from this study that although AHA are common in patients with SLE, their clinical value in this syndrome must, at present, be considered limited.

Adolescent↗
PubMed1992

Multiple complications of the antiphospholipid syndrome with apparent response to aspirin therapy.

We describe a patient with antiphospholipid antibodies who presented with a rapid progression of hemolytic anemia, thrombocytopenia, central retinal vein thrombosis, 2 cerebral thromboses and pulmonary hemorrhage. She was treated with high dose prednisolone, plasma exchange, high dose intravenous immunoglobulin and began taking cyclophosphamide without evidence of control of disease. However, the anemia and thrombocytopenia appeared to respond rapidly to low dose aspirin and she made a complete recovery without any further complications.

Adult↗
PubMed1991

Asymmetrical weakness in polymyositis associated with neuropathic involvement.

Peripheral nerve involvement is rare in polymyositis and dermatomyositis. We describe a patient in whom the clinical appearance was suggestive of a markedly asymmetrical presentation of polymyositis. Nerve conduction studies, however, were consistent with multiple neuropathies and suggest that neurological involvement may have been the basis of the asymmetrical weakness. Both the muscle weakness and the neurological abnormalities resolved with corticosteroid therapy. This case illustrates a previously undescribed neurological complication of polymyositis.

Humans↗
PubMed1990

Antiphospholipid antibodies in systemic lupus erythematosus: clinical and laboratory associations in 111 patients.

An enzyme linked immunosorbent assay (ELISA) was used to evaluate the prevalence and disease associations of antibodies to a range of negatively charged phospholipids in 111 patients with systemic lupus erythematosus (SLE). The frequency of one or more isotypes of different antiphospholipid antibodies (APLs) was similar (range 33%-45%). When individual isotypes were considered alone there was considerable variation (range 5%-32%). There were significant associations between thrombosis, thrombocytopenia, and central nervous system (CNS) disease but not abortion with elevated APL. Strong associations were found between raised anti-ds-DNA (Farr assay) and a positive direct Coomb's test with raised APL. Thus, APLs are common in SLE and are associated with discrete clinical and laboratory features. However, detection of antibodies to a range of negatively charged phospholipids added little clinically useful information to that obtained by measuring anticardiolipin antibody (ACL) alone. We cannot recommend the use of APLs other than ACL for routine testing.

Adolescent↗
PubMed1990

Predicting antigenic determinants of autoantigens.

Predicting antigenic determinants of foreign proteins from their amino acid sequence and/or conformation is of growing importance in the production of synthetic vaccines and antigens. Unlike foreign antigenic proteins, little is known of the suitability of predictive techniques for defining antigenic regions of self proteins recognised by autoantibodies. In this study we describe our use of two computer programmes (HYDRO 3 and ACROPHILICITY [ACRO], Hopp, 1986) for the prediction of antigenic determinants of autoantigens of the cell nucleus. Using the amino acid sequence of the protein, HYDRO 3 and ACRO respectively, provide information on the hydrophilic and surface regions of the protein. Both methods were used to predict the antigenic determinants of known autoantigens, including histones, the A, B", E and 70 kD proteins of snRNPs, SS-B/La, proliferating cell nuclear antigen (PCNA) and others. Our analysis of the antigenic determinants of histones agreed with other studies which have used antihistone antibodies and fragments of histones to show that autoantibody reactive sites reside in the terminal portions of these proteins, particularly the amino terminus. A detailed study of histone 2B correctly identified most regions recognised by antibodies, particularly autoantibodies. In addition the recently described epitope of the autoantigen ribosomal protein P2 was predicted by this analysis. From these observations we hypothesize that linear antigenic sites of self proteins can be predicted. Our hypothesis can be proven experimentally by demonstrating specific interaction between autoantibodies and synthetic peptides homologous with the predicted determinant.

Autoantigens↗
PubMed1989

Antihistone antibodies in rheumatoid arthritis and Felty's syndrome.

Although antihistone antibodies are frequently detected in patients with systemic lupus erythematosus, they appear to be uncommon or present only at low levels in rheumatoid arthritis (RA) patients. We used an enzyme-linked immunosorbent assay to study sera from 42 patients with RA, and we confirmed that antihistone antibodies mainly occurred at low levels in these patients. In contrast, 83% of 24 patients with Felty's syndrome had antihistone antibodies, often at high levels. Thus, antihistone antibodies may be a common autoimmune abnormality in patients with Felty's syndrome but not in other patients with RA. In addition, we demonstrated that some rheumatoid factors have cross-reactive antihistone antibody activity.

Arthritis, Rheumatoid↗
PubMed1989

Lymphocyte migration patterns in autoimmune MRL-lpr/lpr mice: relationship to age, disease manifestations and lymphocyte homing receptor expression.

We have previously reported that lymphoid cells from systemic lupus erythematosus (SLE) mice with established disease migrate aberrantly. This study evaluates the abnormal lymphocyte migration patterns found in MRL-lpr/lpr (MRL/l) mice in relation to age, disease manifestations and the expression of lymphocyte homing receptors. 51chromium-labelled lymph node cells from MRL/l and from normal histocompatible CBA mice of different ages were injected i.v. into age and sex-matched CBA recipients. Diminished lymph node and increased hepatic uptake of MRL/l compared to CBA cells was evident as early as 6 weeks of age. Abnormalities in lymphocyte migration antedated the appearance of elevated antihistone antibody (AHA) levels but not the development of lymphadenopathy. Using the monoclonal antibody MEL-14, no differences in the expression of lymphocyte homing receptors between MRL/l and CBA lymph node cells were found at any age. Thus abnormalities in lymphocyte migration in MRL/l mice appear as early as six weeks and are not related to changes in homing receptor expression.

Age Factors↗
PubMed1989

Mid-infrared lasers for endoscopic surgery. A new class of surgical lasers.

Unlike the Nd:YAG, the CO2 laser produces well circumscribed tissue removal with little unwanted damage because of its high absorption coefficient relative to tissue water. Unfortunately, conventional quartz fibers cannot transmit wavelengths greater than three microns, well below the ten micron wavelength of the CO2 laser. Thus, fiberoptic transmission of CO2 laser requires use of exotic materials that lack the excellent properties of quartz fibers and that, in some cases, are toxic or chemically unstable. However, there are large peaks in the infrared absorption curve of water in the two to three micron region. Lasers that operate in this mid-infrared region should permit CO2-like precision of cutting, along with excellent transmission through quartz fiberoptics. Two mid-infrared lasers with a fiberoptic delivery system, the Er:YAG (2.94 micron) and the Tm-Ho-Cr:YAG (2.15 micron) have been evaluated with human colon tissue in vitro and with rabbit gastric tissue in vivo. Histologic sections reveal excellently well localized lesions with minimal underlying thermal damage. Depth of penetration is controllable and occurs in very small increments. There is little spreading of the lesions at the 24 hour mark resulting from secondary thermal damage. Based on these facts, the authors think that these lasers will be of benefit to endoscopic surgeons.

Animals↗
PubMed1988

Preliminary evaluation of a pulsed 2.15-micron laser system for fiberoptic endoscopic surgery.

There is a need for lasers that are compatible with fiberoptic endoscopes and that provide greater cutting precision than currently can be produced by the widely used Nd:YAG (1.06 micron) laser. Recently available lasers that operate in the 2-micron region fill this need. This laser light energy can be transmitted by low OH- silica fibers and has much less tissue penetration than radiation at 1.06 micron. We have been evaluating a prototype solid state laser system that produces pulses of 2.15 microns light that is delivered by a silica based fiberoptic delivery system with negligible transmission losses. This system is based on a thulium-holmium-chromium doped YAG (Tm-Ho-Cr: YAG) rod that lases at 2.15 micron. The laser does not require cryogenic cooling, toxic gases, or custom utilities and should be practical in a clinical environment. In vivo animal testing of this laser confirms that it provides greater ablating precision than does the Nd:YAG laser at 1.06 micron.

Animals↗
PubMed1988

Response of rheumatoid arthritis to chemotherapy for Hodgkin's disease in a patient with IgA deficiency and overlap connective tissue disease.

A patient with IgA deficiency presented with classical rheumatoid arthritis (RA) and subsequently, features of multiple other connective tissue diseases (CTD). When Hodgkin's disease later developed the patient received combination chemotherapy, which induced remission of both neoplastic and connective tissue diseases. As the RA remained in remission for three years this case may offer insight into a mode of use of cytotoxic agents in CTD.

Adult↗