Ultra-short acting beta-blockers: a proposal for the treatment of the critically ill patient

Beta-blockade is of proven value in the therapy of acute myocardial infarction but, unfortunately, may produce cardiac failure by removal of needed sympathetic support. The long duration of action of available blockers (hours) makes reversal of failure a complicated problem and precludes rapid modification of therapy to match changing autonomic conditions. To improve the safety and efficacy of beta-blockade in this setting we have developed the concept of ultra-short beta-blockade and have identified a novel beta-blocker (ASL-8052) which possesses a duration of action less than 15 minutes. This compound is cardioselective and possesses efficacy in an animal model of acute myocardial infarction. It, therefore, appears to be suitable for rapid attainment of controlled levels of beta-blockade via intravenous infusion and rapid recovery from beta-blockade if required by the clinical situation. The compound should, therefore, be useful for safe therapy in critically ill cardiac patients.     

Surgery in Management of Patients with Leukaemia

Though leukaemia is not a “surgical” disease, the need for surgery in patients with leukaemia is increasing. Acute surgical problems in such patients present diagnostic difficulties, and accepted surgical principles do not necessarily apply in patients with very abnormal haematological and immunological features. The improved prognosis in some types of leukaemia means that elective surgical procedures, which formerly would not have been considered, may now be applicable just as they would be in patients with non-malignant conditions.Recent advances in the management of the leukaemias include several surgical procedures—for example, to facilitate intravenous or intrathecal therapy. Splenectomy is of value in chronic lymphocytic leukaemia when the correct indications are present, while early elective splenectomy, when no classical indications are present, may have a useful role in the management of patients with chronic granulocytic leukaemia.     

NONSPECIFIC ANTI-INFLAMMATORY AGENTS—Some Notes on Their Practical Application,Especially in Rheumatic Disorders

A number of acute and chronic inflammatory disorders are amenable to varying degrees of therapeutic control with the administration of nonspecific anti-inflammatory drugs. An evaluation of these suppressive agents in the field of rheumatic diseases and practical suggestions regarding their administration are presented.Eight synthetically modified corticosteroid compounds are available commercially. Each of them exhibits qualitative differences in one or several physiologic actions, each has certain advantages and disadvantages in therapy, and each shares the major deterrent features of corticosteroids. Prednisone, prednisolone, methylprednisolone, fluprednisolone and paramethasone have similar therapeutic indices, and there is little choice between them for the usual rheumatoid patient requiring steroid therapy. Conversely, the therapeutic indices of dexamethasone, betamethasone and triamcinolone are lower than that of prednisolone; they are less desirable for routine use and should be reserved for specially selected cases.Salicylates are preferred to adrenocortical steroids in the treatment of the ordinary patient with acute rheumatic fever. Steroid therapy should be reserved for resistant cases and for those with significant carditis. Salicylates are mainstays for pain relief in rheumatoid arthritis, but with the analgesic doses usually employed their anti-inflammatory action is slight.Phenylbutazone is a highly useful anti-inflammatory agent, especially in management of acute gouty arthritis and ankylosing (rheumatoid) spondylitis; its metabolite, oxyphenylbutazone, does not exhibit clear-cut advantages.Colchicine specifically suppresses acute gouty arthritis. Its analogues, desacetylcolchicine and desacetylthiocolchicine, produce fewer unpleasant gastrointestinal symptoms, but may promote agranulocytosis and alopecia.A number of indole preparations with anti-inflammatory activity have been tested clinically. One of them, indomethacin, has received extensive therapeutic trial; with dosages that can be tolerated the drug is fairly effective in the symptomatic control of ankylosing (rheumatoid) spondylitis but it is of questionable value in peripheral rheumatoid arthritis.     

Ticlopidine hydrochloride use and threatened stroke.

Ticlopidine hydrochloride is an antiplatelet agent of proven antithrombotic efficacy that in December 1991 became available for general clinical use in the United States. The relative value of ticlopidine compared with aspirin, also an effective antiplatelet agent, has become a key clinical issue. Whereas ticlopidine is somewhat more effective than aspirin for preventing stroke in certain populations, it is also more expensive and potentially toxic. We recommend its use for patients with threatened stroke who are intolerant of aspirin and for patients who have cerebral ischemic symptoms despite aspirin therapy. Patients surviving major ischemic stroke make up a third group for whom ticlopidine use may be recommended in preference to aspirin. The use of ticlopidine rather than aspirin in patients with other cerebrovascular conditions is not strongly supported by existing data. The risk-benefit-cost equation involving ticlopidine versus other antithrombotic therapies is complex, rendering a wide range of acceptable management practices. If reliable laboratory monitoring for neutropenia during the first 3 months of therapy is not feasible, ticlopidine should not be used.     

Strongyloidiasis associated with amebiasis and giardiaisis in an immunocompetent boy presented with acute abdomen

Strongyloides stercoralis (SS) is an intestinal nematode that is mainly endemic in tropical and subtropical regions and sporadic in temperate zones. SS infection frequently occurs in people who have hematologic malignancies, HIV infection and in individuals undergoing immunosuppressive therapy. In this study, we report a 12- year-old immunocompetent boy who was admitted to our hospital with acute abdomen. Laboratory evaluation showed strongyloidiasis, amebiasis and giardiasis. Clinical and laboratory findings immediately improved with albendazole therapy. Therefore, when diarrhea with signs of acute abdomen is observed, stool examinations should be done for enteroparasitosis. This approach will prevent misdiagnosis as acute abdomen. Complete clinical improvement is possible by medical therapy without surgical intervention.     

INTESTINAL OBSTRUCTION COMPLICATING ACUTE PERFORATIVE APPENDICITIS

Upon preoperative diagnosis of acute small bowel obstruction, without an obvious cause, acute perforative appendicitis must be considered. Reevaluation of the history and careful reexamination of the physical findings with that diagnosis in mind should be carried out. If appendiceal disease is likely, maximum antibiotic therapy must be begun immediately along with the administration of fluids, electrolytes and other corrective therapy. A mercury-weighted small bowel tube should be inserted and every effort made to advance it into the small bowel before operation. Operative treatment should be restricted to the least possible. A McBurney incision is best unless wider operation is indicated. If an abscess is present, drainage alone may be the procedure of choice. Severely distended and decompensated small bowel must be decompressed, for if not relieved it can be the cause of death in acute perforative appendicitis. Decompression may be accomplished either by small bowel intubation with continuous suction or by enterotomy and aspiration. If not relieved, small bowel distention will be the mechanism responsible for death in a large percentage of patients with acute perforative appendicitis.     

Beta-blocker therapy and the risk of anaphylaxis.

Beta-blocker therapy is associated with an increase in the severity and, possibly, the incidence of acute anaphylaxis. The population at risk consists of people with allergic conditions who are given a beta-blocker for an unrelated condition. Anaphylaxis under these conditions may be severe, protracted and resistant to conventional treatment because of the beta-adrenergic blockade. Severe or fatal attacks have been triggered by insect stings, the ingestion of allergenic foods or drugs, and injections of radiocontrast media, antisera or immunotherapy antigens. These occurrences are probably infrequent, but their incidence is unknown. At least two fatal cases have recently occurred in Canada. Clinical allergists, internists and family practitioners in particular should be aware of the need for aggressive and prolonged support in patients who experience anaphylaxis while receiving beta-blocker therapy and should report all such occurrences to the federal registry of adverse drug reactions. Allergy skin testing or immunotherapy is inadvisable in patients who take a beta-blocker orally or in the form of ophthalmic eyedrops. The list of relative contraindications to beta-blocker use should be extended to include susceptibility to recurrent anaphylaxis, whether it is idiopathic or due to an identifiable cause.     

Early initiation of statin therapy after a coronary event

PURPOSE OF REVIEW: Despite improvements in the early management of acute coronary syndromes, the risk of major cardiovascular complications remains high. Lipid-modifying treatment with statins has the potential to further improve outcomes through improved endothelial function, antithrombotic and antiinflammatory actions. Statins are of proven benefit in patients with stable coronary heart disease. There has been speculation on potential mechanisms of benefit but, until recently, little data on the efficacy and safety of statins in the acute setting. Recent observational studies and randomized trials have addressed some of the questions regarding early initiation of statins in acute coronary syndromes. RECENT FINDINGS: Recent observational and randomized trials have shown that early commencement of statins in acute coronary syndromes is safe as early as 6 hours after the event and is likely to improve longer-term compliance. The current data are not sufficient to draw conclusions about the efficacy of statins early in the course of acute coronary syndromes. SUMMARY: Current management for acute coronary syndromes should include the commencement of statin therapy during initial hospital admission. This recommendation is based on safety and compliance data. More randomized trial evidence is required to determine whether early initiation will produce better outcomes than later initiation after an acute coronary event.     

Continuous renal replacement therapy in children post-hematopoietic stem cell transplantation: the present and the future

Allogeneic hematopoietic stem cell transplantation (HSCT) use has expanded markedly to treat different disorders like hematologic malignancies, immunodeficiency, and inborn errors of metabolism. However, it is commonly associated with complications that limit the benefit of this therapy. Acute renal failure occurs commonly after HSCT and results in increased risk of mortality. In many instances, children post-HSCT develop acute renal insufficiency in the context of other organ failure, necessitating intensive care unit admission for management. Recently, continuous renal replacement therapy (CRRT) has emerged as the favored modality of renal replacement therapy in the care of critically ill children who are hemodynamically unstable. Currently, CRRT is being utilized more often in the care of critically ill post- HSCT children to treat renal failure or to prevent fluid overload (FO). FO > 20% has been shown in many studies to be an independent risk of mortality in critically ill children and therefore, many clinicians will initiate this therapy due to FO even without overt renal failure. CRRT may be beneficial in disease processes as acute lung injury due to removal of fluid. CRRT results in improved oxygenation in post-HSCT children with acute lung injury and this improvement is sustained for at least 48 hours after initiation of this therapy. Survival in post-HSCT children requiring this therapy ranges from 17% to 45%, however, long term survival is still poor. This review will discuss current practice of CRRT in children post-HSCT, as well as future directions.     

The Changing Pattern of Rheumatic Fever in Childhood

The manifestations of acute rheumatic fever were compared in 231 children admitted to hospital from 1937 to 1940 with those in 252 children admitted from 1957 to 1960. Of the 178 in the early group seen during an initial attack, 82 had cardiac involvement; of these, 12 died early. Of the 218 patients in the later group with an initial attack, 96 had cardiac involvement; of these, two died early. Despite this decrease in early mortality, the incidence of isolated mitral value involvement (73% in the early group and 62% in the later group) and the incidence of congestive failure (20% and 13%) were similar. This reduction in the number of early deaths may be due to lowered virulence of the streptococcus, improved socioeconomic conditions, or therapy with penicillin and corticosteroids. The incidence of chorea and the frequency of recurrences were also less in the later group.     

ANTICOAGULANT DRUG TREATMENT OF CORONARY ARTERY DISEASE

Anticoagulant therapy of arteriosclerotic heart disease may prove to be most valuable when applied on a long-term basis for prevention of recurrent myocardial infarction. While its prophylactic value in impending infarction has not been established, at least the accepted treatment for the acute stage is already begun if an anticoagulant has been administered before an inevitable infarction occurs.The chief value of the anticoagulant, though, seems to lie in preventing cardiac mural thrombosis and extracardiac thromboembolism. It is by this effect, apparently, that mortality has been reduced by 50 per cent among survivors of myocardial infarction who receive continuous dicoumarin therapy.While the danger of hemorrhage is still present, it is being steadily reduced by increasing skill in the management of anticoagulant therapy, and for a long time the risk has been far outweighed by the reduction in coronary occlusion.Physicians have a duty to learn the use of anticoagulant therapy, obtain the facilities necessary for it, and apply it to patients who are able and willing to cooperate in prolonging their useful lives.     

Clinical and diagnostic management of toxoplasmosis in the immunocompromised patient

With the advent of the highly active antiretroviral therapy (HAART), the natural course of HIV infection has markedly changed and opportunistic infections including toxoplasmosis have declined and modified in presentation, outcome and incidence. However, TE is a major cause of morbidity and mortality especially in resource-poor settings but also a common neurological complication in some countries despite the availability of HAART and effective prophylaxis. In most cases toxoplasmosis occurs in brain and toxoplasmic encephalitis (TE) is the most common presentation of toxoplasmosis in immunocompromised patients with or without AIDS. The need of a definitive diagnosis is substantial because other brain diseases could share similar findings. Rapid and specific diagnosis is thus crucial as early treatment may improve the clinical outcome. Classical serological diagnosis is often inconclusive as immunodeficient individuals fail to produce significant titres of specific antibodies. Polymerase chain reaction (PCR) has a high diagnostic value in the acute disease, but like many 'in-house' PCR assays, suffers from lack of standardization and variable performance according to the laboratory. Molecular diagnosis of toxoplasmosis can be improved by performing real-time PCR protocols. This article summarises the clinical manifestations, diagnostic procedures and management strategies for this condition.     

EXPERIENCE WITH ACTH AND CORTISONE IN PRIVATE PRACTICE

ACTH and cortisone are highly nonspecific in their action. A fundamental portion of the mechanism of action is the interposition of a blockade between toxin and end organ. This effect can be of great benefit in the management of a variety of acute and chronic diseases.A major hazard constantly to be kept in mind is the potential masking of advancing disease. This consideration makes concomitant chemotherapy mandatory in the presence of specific infections.In chronic diseased states it should be assumed that prolonged therapy will be necessary. Treatment should not be instituted unless such continued therapy is physiologically and economically feasible.     

弱He—Ne激光血管内照射治疗急性缺血性脑血管病疗效及机理探讨

本研究观察了１２０例颈内动脉系统急性缺血性脑血管疾病患者,按单双数随机分入激光综合治疗组（激光组）和常规药物治疗组（药物组）各６０例。均予静脉点滴通脉液５００ｍｌ,川芎嗪１００ｍｇ,每天一次,十天为一疗程,激光组同时予１ＬＬＬ１治疗,照射时间６０分钟,每天一次,十天为一疗程,光纤末端输出功率１．５－２．０ｍＷ,同时予３０例健康志愿者１ＬＬＬ１一次。所有受试者在治疗前后均进行血液流变学指标,纤溶系统指标和ＴＣＤ检测,并评定患者治疗５、１０天的疗效。研究结果证明,１ＬＬＬ１ＩＴ可以提高单一药物治疗的疗效,机制是改善血液流变学性能,改善微循环,增快脑血流速度,而且可能有激活纤溶系统功能的作用。所有接受１ＬＬＬＩＴ者均无明显的不良反应。本临床研究表明,１ＬＬＬＩＴ可作为缺血性脑血管病一项有效的安全的辅助治疗方法。     

Phagedena: gangrenous and necrotic ulcerations of skin and subcutaneous tissue.

Phagedena is an old term for serious deep, necrotic and gangrenous skin ulcers. In the past these have been regarded as severe infections. A review of 31 cases revealed that except in cases of Streptococcus pyogenes or Clostridium welchii infection a bacterial of fungal infection was only one of several factors that led to the development of phagedenic ulcers. Initiating factors may be a bacterial infection, a debilitated state as a result of immunosuppressive therapy or of such conditions as alcoholism, severe diabetes, inflammatory bowel disease or severe arteriosclerosis, and various types of injury or trauma. Continuing factors include enzymatic mechanisms, the release of toxins from large areas of dead tissue and vascular disorders. In general, antibiotics are of limited value. systemic corticosteroid therapy may be useful in the subacute or chronic case. In acute, spreading, gangrenous phagedena with surrounding erythema, fever and systemic toxic effects, immediate excision of dead tissue may be lifesaving.     

Melatonin in clinical oncology

The aim of this article is provide a survey of the current knowledge relating to the analysis of melatonin and its administration to cancer patients. On the basis of this compilation of data it can be discussed under which conditions melatonin may be used for diagnostic and/or therapeutic purposes in clinical oncology. Melatonin is depressed in patients with cancers of different origins during the phase of primary tumour growth whereas a normal or sometimes elevated pineal melatonin secretory activity is found during early stages of tumour development or when recidivations arise. The clinical studies of Lissoni show that melatonin, particularly if combined with interleukin-2, is able to favourably influence the course of advanced malignant disease leading to a prolonged survival as well as to an improved quality of life. These findings require to be verified by independent and controlled replication studies. If they can be confirmed it should be attempted to administer melatonin to patients with earlier stages of cancer parallel to standard oncological treatment regimens. In such trials it should be tested whether a substitutional therapy in patients with endogenously depressed melatonin may favourably affect the course of the disease both in quantitative (inhibitory effect on tumour growth and spread) and qualitative terms (improved performance status).     

Experiences with cortisone given orally

The advantages of the oral administration of cortisone, when compared with cortisone given intramuscularly, include the more rapid appearance of therapeutic effects, which is of importance in the therapy of acute disease, and the faster dissipation of effects when the hormone is discontinued, which is of value when dangerous reactions occur. Oral dose schedules depend upon the degree of urgency or chronicity of the treated disease. In acute diseases the therapeutic results, in general, were disappointing. Cortisone may be of greater value in the long-term maintenance treatment of certain chronic diseases. By long-term therapy the authors mean practically continuous treatment until either the disease goes into spontaneous remission or undesirable effects of the drug require cessation of treatment. Critical selection of patients and constant supervision of therapy are vital to the successful administration of cortisone. Even with these precautions, however, the therapeutic use of cortisone must be regarded as experimental until the passage of time permits better appraisal of harmful effects.     

股骨头缺血坏死介入治疗的临床应用研究

目的:探讨介入治疗股骨头缺血坏死的临床应用价值。方法:采用Seldinger技术对28例患者行超选择股骨头供血动脉插管,动脉造影、溶通治疗。结果:28例患者治疗后髋部疼痛及关节功能障碍均有不同程度的减轻及改善,有效率96.4%;治疗后病变区血管分支增多、增粗;影像随访显示股骨头骨质不同程度修复。结论:介入治疗具有创伤小、并发症低、血管再通率高、临床症状改善明显的优势,能有效的改善股骨头的局部血液循环和髋关节的疼痛、活动功能,应大力推广。     

Surgical Timing in Biliary Tract Disease

Based on 991 cases of biliary tract disease managed in a recent four-year period, the authors contrast an elective operative mortality rate of 0.6% against 4.4% for acute cholecystitis. Because in 21 of 28 patients with acute cholecystitis symptoms and signs subsided within 48 hours of conservative management in hospital, they recommend a two-day trial of conservative management for patients with acute cholecystitis and operation only for those who are not definitely improving under optimal conditions. The incidence and expected mortality from acute cholecystitis increased with age. Where possible, elective operation should be done when stones are first diagnosed because in patients over 65 years of age the rate of complications was four times and the mortality rate three times that in patients under 65. The incidence of cancer in cholelithiasis was sufficiently high that it is a significant factor in the consideration of prophylactic cholecystectomy. Patients with ruptured gall-bladders can present a trap for the unwary diagnostician; they should have minimal emergency surgery.     

PRACTICAL ASPECTS OF THE LOW SODIUM DIET

The advantages of the oral administration of cortisone, when compared with cortisone given intramuscularly, include the more rapid appearance of therapeutic effects, which is of importance in the therapy of acute disease, and the faster dissipation of effects when the hormone is discontinued, which is of value when dangerous reactions occur. Oral dose schedules depend upon the degree of urgency or chronicity of the treated disease. In acute diseases the therapeutic results, in general, were disappointing. Cortisone may be of greater value in the long-term maintenance treatment of certain chronic diseases. By long-term therapy the authors mean practically continuous treatment until either the disease goes into spontaneous remission or undesirable effects of the drug require cessation of treatment. Critical selection of patients and constant supervision of therapy are vital to the successful administration of cortisone. Even with these precautions, however, the therapeutic use of cortisone must be regarded as experimental until the passage of time permits better appraisal of harmful effects.