[Preventing infarct in the diabetic patient. Lowering blood glucose and HbA1c are not enough].
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Biomedical subjects
Publications and source records attributed to T Lander.
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Scientific literature published in the early 1980s claimed that only 15% of medical interventions are based on scientific evidence (57). Lately, a number of published articles concluded that ca. 80% of the interventions in family medicine (18, 25) and ca. 60% of those in psychiatry fulfil these criteria (24). Did medical practice change so fundamentally? Hard to believe. But to what extent do physicians practice evidence-based medicine as newer publications also constitute a level of science-based interventions across all medical disciplines of only 21% (17)? This article tries to highlight and discuss which observations can be made regarding the compliance to principles of 'evidence based medicine' in one of the most important field of medical interventions--drug therapy. Taking the submarkets of cardiovascular and respiratory drugs as an example, the authors try to identify and discuss effects and obstacles to implement evidence-based pharmacotherapy, and how the latter might be overcome in the future.
PURPOSE: The anatomy of individual myofibers within the orbicularis oculi muscle was examined to determine individual myofiber lengths in the different regions of the muscle. A wide variety of eyelid conditions require eyelid surgery or drug injections directly into the eyelid. Knowledge of regional myofiber anatomy and physiology is important for accurate treatment of these conditions. METHODS: Eyelid specimens from rabbits were treated with collagenase, fixed, and stained for neuromuscular junction location. Individual myofibers were dissected from these muscle specimens and were measured to determine individual myofiber length and neuromuscular junction position. Additional eyelid specimens of rabbits and humans were stained en bloc to visualize neuromuscular junction location in the pretarsal and preseptal regions of the orbicularis oculi muscle. RESULTS: The myofibers showed variable lengths, shorter in the pretarsal region of the muscle and longer in the preseptal region. The average individual myofiber length in the pretarsal region was 36% as long as the entire length of the pretarsal muscle region. In the preseptal region, the myofibers were slightly longer, covering 54% of the entire length of this region of the muscle. In both the pretarsal and preseptal regions of the rabbit and human orbicularis oculi muscle, there were many clusters of neuromuscular junctions throughout the medial to lateral length of the muscle, with the majority of the neuromuscular junctions in the medial and lateral canthal regions of the preseptal portion of the lid. This indicates that the muscle is composed of relatively short, overlapping myofibers, and that the shortest myofibers reside in the medial and lateral canthal regions of the eyelid. Multiple innervation of one rabbit myofiber was observed as a rare occurrence. CONCLUSIONS: Individual myofibers of the orbicularis oculi muscle are relatively short, end intrafascicularly, and are of heterogeneous lengths varying regionally within the muscle. Thus, for drug injections into the eyelid, optimal drug effectiveness may require treatment of the entire lid from medial to lateral canthus to overcome the tissue barriers to diffusion. The existence of muscle fibers of heterogeneous lengths suggests that the complex organization of muscle fibers may play previously unappreciated but important roles in normal function, pathophysiology, and age-related changes in the eyelid.
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Flow cytometry was recently introduced for the detection of antibodies in human serum to a cultured insulin-secreting rat insulinoma cell line (RINm5F) to investigate humoral immune reactivity in newly diagnosed type I (insulin-dependent) diabetic patients. Fifty-three patients were observed for 6-20 mo after clinical onset of diabetes with a reported duration of symptoms of less than 6 wk. Human anti-RINm5F antibodies were detected in 28%, human anti-islet cell antibodies in 62%, and anti-insulin autoantibodies in 36% of patients before initiation of insulin therapy. Occurrence of human anti-RINm5F antibodies at this stage was correlated with human anti-insulin autoantibodies rather than with the formation of anti-islet cell antibodies. Incidence of anti-RINm5F antibodies in individuals with duration of diabetes greater than 6 wk was 38%, whereas human anti-islet cell antibodies and anti-insulin antibodies became detectable in 72 and 61% of the patients, respectively. These findings are in line with previous reports of immunoprecipitation by human diabetic serums of a 64,000-Mr antigenic structure in freshly prepared rat islet cells. The results suggest a reactivity of distinct classes of antibodies in serums of patients with type I diabetes to disparate antigens on human islet cells and cloned rat insulinoma cells and, moreover, reactivity to insulin as the secreted product. Further characterization of the reacting RINm5F antigens and prospective studies in subjects at risk for diabetes are required to validate the application of RIN cells to the investigation of immune mechanisms involved in the pathogenesis of human type I diabetes.
Peripheral blood lymphocytes have been investigated in 20 newly diagnosed type-I diabetics and 10 healthy subjects using monoclonal antibodies. Mononuclear cells were marked with anti-T-lymphocytes (Leu2, 3, 4, 12) and anti-Ia-antibodies (K14, L243) using indirect immunofluorescence. The percentage of circulating K14- and L243-positive cells was significantly higher in all diabetics than in normal controls. An increase in the number of K14-bearing cells was found in newly diagnosed patients with duration of less than 7 days (n = 10) compared with diabetics of longer duration (1 to 8 months; n = 10). Using dual-color immunofluorescence with fluorescein-conjugated anti-T-lymphocytes and rhodamin-conjugated anti-Ia-antibodies it was not possible to identify Ia-antigen bearing cells (Ia cells) as helper or suppressor lymphocytes. In addition, there was no significant difference in the number of Ia cells in diabetics with and without islet cell antibodies. It is concluded that there is evidence of activation of cellular immune response in type I diabetes, particularly in the early days of manifestation. However, previous assumptions that Ia cells represent T-cell activation have to be questioned.
Between 1984 and 1987 (over two-and-a-half years) 30 hospitalized patients with HIV infections of different degrees of severity were ophthalmologically examined. Ocular involvement was found in 17 patients (approx. 57%). In 16 of these 17 patients with pathologic ophthalmologic findings (approx. 94%), AIDS was already fully developed. Ocular involvement is therefore a sign of poor prognosis. Fourteen patients had a microvascular retinal syndrome and four patients had infectious (chorio-)retinitis (causative organisms: cytomegalovirus in three cases, Cryptococcus neoformans in one). Further findings included sicca syndrome with superficial punctate keratitis in two cases, keratitis in one patient with generalized mucocutaneous candidiasis, Kaposi's sarcoma of the eyelids in two cases, Kaposi's sarcoma of the conjunctiva in one case, papilledema with cryptococcal meningitis in one case, and atypical hordeolum in one case. Morphologic and pathogenetic aspects of the ophthalmologic findings, their importance and course in AIDS patients, and therapeutic problems are discussed.
Occlusion of a femoro-popliteal Gore-Tex-bypass in two patients could be reopened using local low-dose thrombolytic therapy. Apart from the peripheral outflow effective anticoagulation treatment appears to have a deciding influence on long-term results. Application of the thrombolytic selectively to single vessels of the lower leg as well as a post-lysis effect offer the chance for an improvement in outflow. Combination of local lysis with vessel surgery may be an additional alternative for conservation of the extremities.
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