Topical Hemostatic Agents: A Review

Topical hemostatic agents play an important role in both common and specialized dermatologic procedures. These agents can be classified based on their mechanism of action and include physical or mechanical agents, caustic agents, biologic physical agents, and physiologic agents. Some agents induce protein coagulation and precipitation resulting in occlusion of small cutaneous vessels, while others take advantage of latter stages in the coagulation cascade, activating biologic responses to bleeding. Traditional and newer topical hemostatic agents are discussed in this review, and the benefits and costs of each agent will be provided.     

荧光造影剂的研究与外科应用进展

近年来,精准外科理念下采用荧光造影剂染色引导手术在外科各个领域得到蓬勃发展,它具有帮助指导外科手术,并为外科医师提供实际可见的荧光显像的作用。临床上,荧光造影剂可用于显示肿瘤轮廓并且识别度高,实时引导手术,定位淋巴结转移,发现微小转移病灶,并在术中识别重要的解剖结构,避免可能发生的副损伤。人们对于能介导外科手术的荧光造影剂的研究已经取得了重大进展,包括对经典荧光造影剂如吲哚菁绿、亚甲蓝等的研究和外科应用拓展,以及对新型靶向荧光造影剂如叶酸受体靶向造影剂、基于单克隆抗体的荧光靶向造影剂和智能造影剂等的开发和临床应用。本文将从经典荧光造影剂和新型靶向荧光造影剂两个方面来对荧光造影剂的研究与外科应用进展进行综述。     

Sweet and simple as syrup: A review and guidance for use of novel antihyperglycemic agents for post-transplant diabetes mellitus and type 2 diabetes mellitus after kidney transplantation

Uncontrolled type 2 diabetes mellitus (T2DM) and post-transplant diabetes mellitus (PTDM) increase morbidity and mortality after kidney transplantation. Conventional strategies for diabetes management in this population include metformin, sulfonylureas, meglitinides and insulin. Limitations with these agents, as well as promising new antihyperglycemic agents, create a need and opportunity to explore additional options for transplant diabetes pharmacotherapy. Novel agents including sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1RA), and dipeptidyl peptidase IV inhibitors (DPP4i) demonstrate great promise for T2DM management in the non-transplant population. Moreover, many of these agents possess renoprotective, cardiovascular, and/or weight loss benefits in addition to improved glucose control while having reduced risk of hypoglycemia compared with certain other conventional agents. This comprehensive review examines available literature evaluating the use of novel antihyperglycemic agents in kidney transplant recipients (KTR) with T2DM or PTDM. Formal grading of recommendations assessment, development, and evaluation (GRADE) system recommendations are provided to guide incorporation of these agents into post-transplant care. Available literature was evaluated to address the clinical questions of which agents provide greatest short- and long-term benefits, timing of novel antihyperglycemic therapy initiation after transplant, monitoring parameters for these antihyperglycemic agents, and concomitant antihyperglycemic agent and immunosuppression regimen management. Current experience with novel antihyperglycemic agents is primarily limited to single-center retrospective studies and case series. With ongoing use and increasing comfort, further and more robust research promises greater understanding of the role of these agents and place in therapy for kidney transplant recipients.     

Hydrophilic Polymers with Potassium Salt and Microporous Polysaccharides for Use as Hemostatic Agents

BACKGROUND Postoperative bleeding can lead to complications such as hematoma, infection, dehiscence, and an unscheduled office visit. Topical hemostatic agents can be used to aid in hemostasis.
OBJECTIVE The objective is to familiarize physicians with topical hemostatic agents—hydrophilic polymers with potassium salts (Urgent QR powder) and microporous polysaccharide hemispheres (Bleed-X).
METHODS Two hemostatic agents, microporous polysaccharide hemospheres and hydrophilic polymers with potassium salt, are discussed. The literature is reviewed.
RESULTS Numerous types of hemostatic agents exist. Topical hemostatic agents are safe, cost-effective, and efficient.
CONCLUSION Microporous polysaccharide hemospheres and hydrophilic polymers with potassium salts can be an adjunct to hemostasis after cautery and ligation. Patients can apply hemostatic agents if they experience any bleeding leading to decreased office visits. Hemostatic agents used intraoperatively shorten bleeding time and enable the physician to use less cautery. Using hemostatic agents can lead to fewer hematomas, infections, and office visits.     

Novel therapies for sepsis: a review

BACKGROUND: Over the past 30 years, efforts have been made to identify therapeutic targets in the host response to infection. METHODS: A review of the randomized controlled clinical sepsis trials and meta-analyses of glucocorticoids, mediator-specific anti-inflammatory agents, and anticoagulant agents was performed. RESULTS: The effects of glucocorticoids in sepsis appear to be dose-dependent, with high doses decreasing survival and low doses improving survival. As a class, the mediator-specific anti-inflammatory agents have a small beneficial effect on survival; however, no single agent has demonstrated significant benefit. The treatment effects of these agents appear to be related to the patient's risk of death. As a class, the anticoagulant agents do not improve survival; however, the efficacy of these agents may have been confounded by concurrent heparin therapy. Activated protein C demonstrated a beneficial effect on survival that was dependent on severity of illness. CONCLUSION: Trials of agents directed at altering the host's response during sepsis have had variable results, and it appears that several different factors may alter the efficacy of these agents.     

Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells

Preclinical models for the identification of prostate cancer chemoprevention agents are lacking. Based upon the notion that clinically useful chemoprevention agents should exhibit selective activity against early stage disease, studies were undertaken to assess whether chemoprevention agents selectively inhibited the growth of early stage prostate cancer, as compared to late stage cancer. First, a series of cell and molecular studies were performed, which, when taken together, validated the use of a panel of prostate cell lines as a model of the different stages of carcinogenesis. Next, therapeutic responsiveness to ten different cytotoxic or chemoprevention agents was evaluated. Chemoprevention agents exhibited selective activity against normal and early transformed prostate tissue, whereas cytotoxic agents were non-specific. Selective activity against early versus advanced prostate cancer cells is identified as a potential screening method for chemoprevention agents.Prostate Cancer and Prostatic Diseases (2001) 4, 81-91     

The role of belataceptin transplantation: results and implications of clinical trials in the context of other new biological immunosuppressant agents

Although conventional immunosuppressive agents such as calcineurin inhibitors, have substantially reduced the risk of acute rejection, they have had less impact on the long‐term survival. This is likely to be related to the adverse effects of such agents in terms of impaired renal function, hypertension, and dyslipidemia. These pitfalls of the currently available agents stimulated the research for biologic agents. Several biologic agents are now in development and hold promise for improved long‐term outcomes in renal transplant recipients, particularly in those who receive sub‐optimal organs. This article gives an overview of these new biological agents with particular emphasis on belatacept and their possible impact on short‐ and long‐term outcomes, notably on marginal organs.     

NSF: WHAT WE KNOW AND WHAT WE NEED TO KNOW: Nephrogenic Systemic Fibrosis Risk: Is There a Difference between Gadolinium‐Based Contrast Agents?

Nephrogenic systemic fibrosis (NSF) is a disabling and potentially fatal disease that has been associated with gadolinium-based contrast (GBC) agents. There are five GBC agents approved for use in the United States and another four approved in Europe. The proposed cause of NSF is release of free Gd3+ into tissues in patients with decreased renal function. The number of associated cases and the potential to release free gadolinium is not equal between these agents. Gadodiamide has the largest number of reported cases of NSF followed by gadopentetate dimeglumine and gadoversetamide. The market share of these agents may contribute to the number of reported cases. The pharmokinetics of gadodiamide and gadoversetamide indicate that these two agents are more likely to release free Gd3+ than other GBC agents. Gadoteridol and gadoterate meglumine have a cyclic structure, making them less likely to release free Gd3+, and there is only a single reported case of NSF associated with gadoteridol use alone. Further research into individual agents is needed.     

In vitro effects of chemotherapeutic agents on human osteoblast-like cells

Osteopenia is a complicating problem that may occur during and after treatment for childhood malignancy. Clinical studies suggest that chemotherapeutic agents directly affect osteoblasts in vivo. Since combinations of agents are used for treatment, we individually investigated the chemosensitivity of human osteoblast-like cells to 11 of the chemotherapeutic agents used. The relative chemosensitivity of osteoblast-like cells representing different stages of cell differentiation was also examined. Cell numbers were evaluated following culture of an established human osteoblast-like cell line (MG63) for 3 days with clinically relevant concentrations of the chemotherapeutic agents. The chemosensitivity of MG63 cells was compared to that of a human osteoprogenitor cell line (HCC1) and primary osteoblast-like (HOB) cells derived from pediatric bone. Cell numbers were reduced by all agents in all cell types, although there was a varied response between agents at equimolar concentrations. In MG63 cells the lowest concentration of agent significantly reducing cell numbers varied between agents, for example, methotrexate (10(-7) M), vincristine (10(-9) M), and etoposide (10(-7) M) (all P <0.01). The less differentiated osteoblast phenotypes were significantly more chemosensitive at equimolar concentrations of methotrexate, vincristine, asparaginase, and dexamethasone than more differentiated phenotypes (all P <0.01). Furthermore, four agents significantly increased alkaline phosphatase (AP) activity in HOB cells. We conclude that individual chemotherapeutic agents added to osteoblast cell cultures reduce cell numbers, with osteoblast precursor cells being preferentially depleted. These results suggest that most of the agents may contribute to osteopenia in childhood malignancy by direct effects on cell numbers.     

Muscle relaxants in ambulatory anesthesia

Neuromuscular blocking agents are used to facilitate tracheal intubation and surgical procedure in ambulatory anesthesia. However, the ideal neuromuscular blocking agents for ambulatory anesthesia are not yet available. The only depolarizing neuromuscular blocking agent, suxamethonium, is still widely used by its rapid onset and short duration of action producing excellent intubating conditions, in spite of its numerous adverse effects. Nondepolarizing neuromuscular agents have proved to be associated with postoperative residual block more frequently than it was thought before. The use of neostigmine for reversal and the measurement of the TOF ratio during recovery are recommended after intermediate-acting neuromuscular blocking agents. Some studies have shown that tracheal intubation without neuromuscular agents may be associated with postoperative hoarseness and vocal cord injuries. Sugammadex will resolve many issues in using nondepolarizing neuromuscular agents in ambulatory anesthesia.     

联合应用9-顺式维甲酸和化疗药物对人胆管癌细胞系QBC939的作用

目的 观察联合应用分化诱导剂9—cis RA和化疗药物对人胆管癌细胞QBC939细胞的作用，为临床诱导分化治疗胆管癌提供实验基础。方法 以10^-6mol／L的9—cis RA作用于培养的人胆管癌细胞系QBC939细胞1、2、3、5d后检测几种常用化疗药物对细胞的杀伤作用。并观察同时加入10^-6mol／L的9—cis RA和化疗药物对QBC939细胞的杀伤作用。结果 同时应用9—cis RA和化疗药物时，对QBC939细胞的杀伤作用与单用化疗药物时无明显差异。9—cis RA作用2d和3d时，化疗药物对QBC939细胞的杀伤作用强于9—cis RA作用前；9—cis RA作用5d时，化疗药物对QBC939细胞的作用较9—cis RA作用前强，但比3d时下降。结论 先用9—cis RA作用后可增强QBC939细胞对化疗药物的敏感性，此作用与9—cis RA作用时间有关。不同联合用药方法的效果不同。     

Inhalational anaesthetic agents

The continued development of anaesthetic agents since the late 18th century has paved the way for the progression of surgical techniques. Inhalational agents are used worldwide for the delivery of safe, effective anaesthesia. These include the volatile agents halothane, isoflurane, sevoflurane and desflurane, in addition to the anaesthetic gases nitrous oxide and xenon. Although the newer volatiles have an improved safety profile in comparison to older agents, the ideal anaesthetic agent remains elusive. It is vital for anaesthetists to understand the physical properties, pharmacodynamics and pharmacokinetics of the individual inhalational anaesthetic agents so that the most appropriate agent for a patient or procedure is selected and administered correctly.     

Conventional chemotherapeutic agents combined with DMSO or DFMO in treatment of rat prostate carcinoma

Chemotherapy for prostatic carcinoma is usually reserved for those patients who have failed conventional therapy. These patients generally are in poor health and tolerate chemotherapy poorly. If doses of conventional agents could be decreased without altering cytotoxic activity, then conventional chemotherapy could become an attractive treatment modality. Dimethylsulfoxide and difluoromethylornithine have been shown to induce differentiation in some tumor systems. Growth alteration effects of these two agents were investigated individually and in association with conventional chemotherapeutic agents cyclophosphamide, cisplatin, and fluorouracil in an experimental prostatic cancer model. Copenhagen rats had subcutaneous tumors induced by injections of cells cultured in vitro from a subline of the Dunning rat prostatic tumor, MAT LyLu. Treatment with chemotherapeutic agents individually and associated with differentiation agents was initiated when tumors were palpable. Tumor growth rates and rat body weights were monitored in all groups. The differentiation agents used singly were not able to retard significantly tumor growth rates. In higher doses, each conventional agent used singly significantly retarded tumor growth. Used in combination, the differentiation agents induced cytodestructive properties of lower doses of conventional agents, but some combinations also increased host toxicity. These data suggest that differentiation agents may provide additional antineoplastic benefits when administered in combination with selected chemotherapeutic agents in the management of prostatic cancer.     

Evaluation of the effect of pharmacologic agents on crush-avulsion arterial injuries: a scanning electron microscopy study.

This study was designed to investigate the short-term formation and composition of thrombus occurring at sites of arterial intimal injury in rabbits. Anti-coagulants, platelet anti-aggregation agents, and fibrinolytic agents were evaluated for their influence upon the developing thrombus, utilizing scanning electron microscopy to determine thrombus surface composition. These agents included: heparin, aspirin, dextran 40, streptokinase, and prostacyclin. The results are consistent with the known nature of each of these agents. When two agents were given simultaneously, each acting on different aspects of thrombogenesis (platelets vs. fibrin), the outcome appeared synergistic, with substantial reduction in thrombus accumulation; clear inhibition of both platelet aggregation and fibrin polymerization was noted. These findings support the clinical use of two agents used simultaneously, one inhibiting fibrin strand formation and the other inhibiting platelet adherence aggregation, for the prevention of micro-arterial thrombosis.     

Use of thrombolytics in vascular and endovascular surgery

Until recently, acute arterial or venous thromboses were routinely managed with surgical intervention. With the development of effective thrombolytic pharmacologic agents and improved modes of delivery of these agents to the target site, surgery is no longer the only option. Greater understanding and knowledge about the finely orchestrated, counterbalanced processes of coagulation and fibrinolysis/thrombolysis have enabled development of agents and strategies for pharmacologic restoration of vascular patency while reducing or eliminating the need for surgery. An evidence-based rationale now exists for the use of thrombolysis in acute limb ischemia, deep venous thrombosis, stroke, and arteriovenous vascular access thromboses. Thrombolytic agents are valuable ancillary agents that allow a less invasive solution to a variety of thrombotic vascular conditions. Strategies that combine thrombolytic agents with endovascular techniques provide precise delivery of these drugs to the target thrombus. A more widespread adoption of this strategy has been limited primarily owing to problems with the currently available pharmacologic agents. The future of thrombolysis therapy is discussed in terms of data obtained from ongoing and recently completed clinical trials. Efforts to develop and study new thrombolytic agents that act directly on the thrombus without activation of intermediary biochemical steps will provide the next major step forward, as well as the rational basis for expansion of currently accepted indications for the treatment of acute arterial and venous thromboses.     

Role of secondary hormonal therapy in the management of recurrent prostate cancer

Androgen ablation remains the cornerstone of the systemic management of prostate cancer. After initial androgen deprivation, clinical outcomes vary considerably. For the patient with progressive disease after androgen deprivation, multiple therapeutic options are available and include antiandrogen withdrawal, chemotherapy, and secondary hormonal agents. Multiple secondary hormonal agents have clinical activity and the sequential use of these agents may lead to prolonged periods of clinical response. In addition to the use of oral antiandrogens, active secondary hormonal therapies include adrenolytic agents such as ketoconazole and aminoglutethimide, corticosteroids and estrogenic compounds. This article reviews the clinical trial data for these various agents and discusses their role in the management of patients with advanced prostate cancer.     

Pharmacological protection of rabbit kidneys from normothermic ischemia.

This study investigated the influence of the administration of pharmacological agents on the recovery of rabbit kidneys from the effects of 1 hr of situ normothermic ischemia, utilizing acute and chronic models. The agents tested included the diuretics mannitol and furosemide, the vasoactive agents phenoxybenzamine, propranolol, and dopamine, and the membrane stabilizers chlorpromazine and methylprednisolone. A beneficial effect was detected only with the diuretic agents and propranolol when given prior to the ischemic insult.     

A program for continuous infusion of cardiovascular agents (CIRCULATION)--how to derive the algorithm and how to use the mathematical formula in this program]

Recently, many cardiovascular agents came to be administered to serious or perioperative cases continuously, and difficult calculation became necessary. For continuous infusion of cardiovascular agents, we devised a personal computer program (CIRCULATION) to avoid difficult calculation for PC-9801 series (NEC) by a C language (Turbo-C, Version 2.0). It is easy to use the program, and it calculates the algorithm for many cardiovascular agents in a second. The program is very useful for anesthesiologists and for other doctors when they administer various cardiovascular agents.     

Disasters and mass casualties: II. explosive, biologic, chemical, and nuclear agents

Terrorists' use of explosive, biologic, chemical, and nuclear agents constitutes the potential for catastrophic events. Understanding the unique aspects of these agents can help in preparing for such disasters with the intent of mitigating injury and loss of life. Explosive agents continue to be the most common weapons of terrorists and the most prevalent cause of injuries and fatalities. Knowledge of blast pathomechanics and patterns of injury allows for improved diagnostic and treatment strategies. A practical understanding of potential biologic, chemical, and nuclear agents, their attendant clinical symptoms, and recommended management strategies is an important prerequisite for optimal preparation and response to these less frequently used agents of mass casualty. Orthopaedic surgeons should be aware of the principles of management of catastrophic events. Stress is less an issue when one is adequately prepared. Decontamination is essential both to manage victims and prevent further spread of toxic agents to first responders and medical personnel. It is important to assess the risk of potential threats, thereby allowing disaster planning and preparation to be proportional and aligned with the actual casualty event.     

Comparative cytotoxicity of ionic and non-ionic radiocontrast agents on MDCK cell monolayers in vitro.

BACKGROUND: Intravascular radiocontrast agents may cause acute renal failure, particularly in patients with pre-existing renal insufficiency. Direct cytotoxic effects of radiocontrast agents on renal tubular cells may contribute to the pathogenesis of radiocontrast-induced nephropathy. METHODS: We analysed the cytotoxicity of the ionic radiocontrast agents diatrizoate (monomeric) and ioxaglate (dimeric), as well as of the non-ionic radiocontrast agents iohexol (monomeric) and iodixanol (dimeric) on the renal epithelial Madin Darby Canine Kidney (MDCK) cell line grown on permeable supports. The toxicity assays assessed cell viability, transmonolayer resistance and inulin permeability between the apical and basal cell culture compartment. In addition, the distribution of the tight-junction-associated membrane proteins ZO-1 and occludin was analysed using immunofluorescence microscopy. RESULTS: In all assays the high osmolal ionic compound diatrizoate had significant cytotoxic effects that included the partial redistribution of the tight-junction-associated membrane proteins into a cytoplasmic compartment. To a lesser extent this redistribution also occurred with the dimeric ionic compound ioxaglate, but not with the non-ionic radiocontrast agents. With regards to cell viability, transmonolayer resistance and inulin permeability the radiocontrast agents with reduced osmolality were significantly less toxic than diatrizoate, independent of their ionic strength. CONCLUSIONS: Physicochemical factors contribute to the cytotoxicity of radiocontrast agents in vitro. The redistribution of tight-junction-associated membrane proteins by the ionic radiocontrast agents corresponds with the loss of the barrier function of the epithelial cell monolayer, which is a major pathophysiological mechanism in acute renal failure. The radiocontrast agents with reduced osmolality are less cytotoxic than diatrizoate, independent of their ionicity. Hyperosmolality appears to be a more important determinant of the cytotoxicity of diatrizoate than ionic strength.