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Biomedical subjects

P C A Kam

Publications and source records attributed to P C A Kam.

17 recordsLinked to original sources

Transfusion-related acute lung injury: a literature review.

Transfusion-related acute lung injury (TRALI) is a serious and potentially fatal complication of transfusion of blood and blood components. TRALI is under-diagnosed and under-reported because of a lack of awareness. A number of models have been proposed to explain the pathogenesis of TRALI: an antibody mediated model; a two-event biologically active mediator model; and a combined model. TRALI can occur with any type of blood product and can occur with as little as one unit. Its presentation is similar to other forms of acute lung injury and management is predominantly supportive. The main strategy in combating TRALI is prevention both through manipulation of the donor pool and through clinical strategies directed at reducing transfusion of blood products including, but not limited to, evidence-based lower transfusion thresholds. This article presents a review of TRALI and addresses the definition, pathology, pathogenesis, clinical manifestations, treatment and prevention of the syndrome.

Humans↗

Direct thrombin inhibitors: pharmacology and clinical relevance.

Although heparin has been a cornerstone of treatment for the prevention of thrombosis, it is limited by its adverse effects and unpredictable bioavailability. Direct thrombin inhibitors are a novel class of drugs that have been developed as an effective alternative mode of anticoagulation in patients who suffer from heparin-induced thrombocytopaenia, and for the management of thromboembolic disorders and acute coronary syndromes. The main disadvantages of the direct thrombin inhibitors are the lack of an antidote or readily available clinical monitoring. The mechanism of action, the properties of direct thrombin inhibitors and their potential to replace currently available anticoagulants are reviewed.

Anticoagulants↗

Anabolic steroid abuse: physiological and anaesthetic considerations.

This review summarises the physiological and pharmacological effects of the anabolic steroids used to enhance performance in sports. The anabolic steroids promote muscle growth and protein synthesis. Side-effects of anabolic steroids include cardiomyopathy, atherosclerosis, hypercoagulopathy, hepatic dysfunction, and psychiatric and behavioural disturbances. It is therefore appropriate that the anaesthetist be familiar with the abuse of anabolic steroids, their potential adverse effects, and the peri-operative risk associated with the use of these drugs.

Anabolic Agents↗

Obesity: basic science and medical aspects relevant to anaesthetists.

Obesity is becoming a major public health problem throughout the world. It is now the second leading cause of death in the United States and is associated with significant, potentially life-threatening co-morbidities. Significant advances in the understanding of the physiology of body weight regulation and the pathogenesis of obesity have been achieved. A better understanding of the physiology of appetite control has enabled advances in the medical and surgical treatment of obesity. Visceral or abdominal obesity is associated with an increased risk of cardiovascular disease and type 2 diabetes. Various drugs are used in the treatment of mild obesity but they are associated with adverse effects. Surgery has become an essential part of the treatment of morbid obesity, notwithstanding the potential adverse events that accompany it. An appreciation of these problems is essential to the anaesthetist and intensivist involved in the management of this group of patients.

Anesthetics↗

An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia.

Acute hypersensitivity reactions to chlorhexidine in the operating room are probably more likely to occur during the early phases of anaesthesia because chlorhexidine is often used for cleaning the surgical field or during placement of indwelling catheters. We report a case of an acute hypersensitivity reaction that occurred in the post anaesthetic care unit. Subsequent skin testing suggested sensitivity to chlorhexidine, which had been applied over the vaginal mucosa at the end of surgery. Relevant issues in the investigation of acute hypersensitivity reactions in the post anaesthetic period are discussed.

Acute Disease↗

Double isolated limb infusion with cytotoxic agents for recurrent and metastatic limb melanoma.

Metastatic melanoma confined to a limb can be treated effectively by isolated limb infusion (ILI) with cytotoxic drugs. The present study was undertaken to determine whether electively performing a second ILI procedure after 4 weeks increases the frequency and/or duration of response, and also to assess the value of a second ILI when disease recurrence or progression in a limb occurs after a first ILI. In 47 patients, a planned double ILI protocol achieved an overall response (OR) rate of 88% (complete response (CR) 41%, partial response (PR) 47%, median duration of response 18 months). Response rates after double ILI were similar to those in 81 patients treated with a single ILI over the same time period (CR 41%, PR 41%), without significant differences in response duration. After double ILI more patients experienced Wieberdink Grade III or IV limb toxicity. Following a second ILI for progression after an initial ILI (n=14), the OR rate was 71%, with a 5 month median duration of response. Since elective double ILI increases toxicity without increasing efficacy, performance of a single ILI is the preferred treatment option for melanoma confined to a limb. However, a second ILI can be of value if limb disease recurs or progresses following a previous ILI.

Aged↗

Isolated limb infusion with fotemustine after dacarbazine chemosensitisation for inoperable loco-regional melanoma recurrence.

BACKGROUND: Isolated limb infusion (ILI) is a simple yet effective alternative to conventional isolated limb perfusion for the treatment of advanced melanoma of the extremities. PATIENTS AND METHODS: The study group comprised 13 patients with very advanced limb disease who had failed to achieve a satisfactory response to one or more ILIs with melphalan, and in whom amputation was the only other realistic treatment option. The aim of this study was to evaluate the efficacy and toxicity of ILI with fotemustine after systemic chemosensitisation with dacarbazine (DTIC). RESULTS: Complete remission was achieved in four patients and partial remission in eight patients, with a median response duration of 3 months. Limb salvage was achieved in five of 12 assessable patients (42%). Limb toxicity peaked 9 days after ILI; two patients experienced Wieberdink grade IV (severe) toxicity and four patients had grade V toxicity (requiring early amputation). CONCLUSIONS: ILI with fotemustine after DTIC chemosensitisation can be successful when gross limb disease has not been controlled by one or more ILIs with melphalan. However, it cannot be recommended as a routine method of treatment for advanced melanoma of the extremities because of the high incidence of severe limb toxicity.

Aged↗

Thrombocytopenia in the parturient.

Thrombocytopenia in pregnant women can be associated with substantial maternal and neonatal morbidity. It may result from a range of conditions and early implementation of some specific treatment may improve both maternal and neonatal outcome. In this review we discuss the clinical features of the more common causes of thrombocytopenia associated with pregnancy, and provide an overview of the anaesthetic considerations.

Anesthesia, Obstetrical↗

Tissue factor and tissue factor pathway inhibitor.

The classical 'cascade/waterfall' hypothesis formulated to explain in vitro coagulation organised the amplification processes into the intrinsic and extrinsic pathways. Recent molecular biology and clinical data indicate that tissue factor/factor-VII interaction is the primary cellular initiator of coagulation in vivo. The process of blood coagulation is divided into an initiation phase followed by a propagation phase. The discovery of tissue factor pathway inhibitor further supports the revised theory of coagulation. Tissue factor is also a signalling receptor. Recent evidence has shown that blood-borne tissue factor has an important procoagulant function in sepsis, atherosclerosis and cancer, and other functions beyond haemostasis such as immune function and metastases.

Animals↗

Mast cell tryptase: a review of its physiology and clinical significance.

Mast cells, which are granulocytes found in peripheral tissue, play a central role in inflammatory and immediate allergic reactions. beta-Tryptase is a neutral serine protease and is the most abundant mediator stored in mast cell granules. The release of beta-tryptase from the secretory granules is a characteristic feature of mast cell degranulation. While its biological function has not been fully clarified, mast cell beta-tryptase has an important role in inflammation and serves as a marker of mast cell activation. beta-Tryptase activates the protease activated receptor type 2. It is involved in airway homeostasis, vascular relaxation and contraction, gastrointestinal smooth muscle activity and intestinal transport, and coagulation. Serum mast cell beta-tryptase concentration is increased in anaphylaxis and in other allergic conditions. It is increased in systemic mastocytosis and other haematological conditions. Serum beta-tryptase measurements can be used to distinguish mast cell-dependent reactions from other systemic disturbances such as cardiogenic shock, which can present with similar clinical manifestations. Increased beta-tryptase levels are highly suggestive of an immunologically mediated reaction but may also occur following direct mast cell activation. Patients with increased mast cell beta-tryptase levels must be investigated for an allergic cause. However, patients without increased mast cell tryptase levels should be investigated if the clinical picture suggests severe anaphylaxis.

Anaphylaxis↗

Vasopressin and terlipressin: pharmacology and its clinical relevance.

Vasopressin and its analogue, terlipressin, are potent vasopressors that may be useful therapeutic agents in the treatment of cardiac arrest, septic and catecholamine-resistant shock and oesophageal variceal haemorrhage. The aim of this article is to review the physiology and pharmacology of vasopressin and summarise its efficacy and safety in clinical trials and its subsequent therapeutic use. Recent studies indicate that the use of vasopressin during cardiopulmonary resuscitation may improve the survival of patients with asystolic cardiac arrest. Vasopressin deficiency can contribute to refractory shock states associated with sepsis, cardiogenic shock and cardiac arrest. Low doses of vasopressin and terlipressin can restore vasomotor tone in conditions that are resistant to catecholamines, with preservation of renal blood flow and urine output. They are also useful in reducing bleeding and mortality associated with oesophageal variceal haemorrhage. The long-term outcome of the use of these drugs is not known.

Animals↗

The thienopyridine derivatives (platelet adenosine diphosphate receptor antagonists), pharmacology and clinical developments.

The thienopyridines, ticlopidine and clopidogrel, are antiplatelet drugs. They are prodrugs and are metabolised in the liver to active metabolites that are non-competitive antagonists of the platelet adenosine diphosphate receptor, P2Y12. Inhibition of platelet aggregation by these drugs is delayed until 24-48 h after administration, with maximal inhibition achieved after 3-5 days. Recovery of platelet function after drug withdrawal is slow (7-14 days). Ticlopidine and clopidogrel are effective in preventing atherothrombotic events in cardiovascular, cerebrovascular and peripheral vascular disease. Gastrointestinal side effects and skin rashes are common. However, neutropenia and thrombotic thrombocytopenic purpura are significant and sometimes fatal adverse effects of ticlopidine. Clopidogrel appears to offer several advantages over ticlopidine: a more rapid onset of action and a lower incidence of neutropenia and thrombotic thrombocytopenic purpura.A combination of clopidogrel and aspirin has become standard for antithrombotic therapy in cardiovascular disease. The anaesthetic considerations of patients taking the thienopyridine compounds are discussed.

Anesthesia↗

Gabapentin: pharmacology and its use in pain management.

Although its exact mode of action is not known, gabapentin appears to have a unique effect on voltage-dependent calcium ion channels at the postsynaptic dorsal horns and may, therefore, interrupt the series of events that possibly leads to the experience of a neuropathic pain sensation. Gabapentin is especially effective at relieving allodynia and hyperalgesia in animal models. It has been shown to be efficacious in numerous small clinical studies and case reports in a wide variety of pain syndromes. Gabapentin has been clearly demonstrated to be effective for the treatment of neuropathic pain in diabetic neuropathy and postherpetic neuralgia. This evidence, combined with its favourable side-effect profile in various patient groups (including the elderly) and lack of drug interactions, makes it an attractive agent. Therefore, gabapentin should be considered an important drug in the management of neuropathic pain syndromes.

Acetates↗

The peri-operative implications of herbal medicines.

An increasing number of patients are taking herbal medicines such as echinacea, garlic, ginkgo biloba, ginseng, St John's Wort, valerian, ephedra, kava, grapefruit juice and ginger. Although these herbal medications are considered 'natural' products that may have some benefits, adverse effects such as increased bleeding tendencies and drug interactions are associated with their use. Surgeons and anaesthetists may be unaware of their patients' use of these medications because it is common for patients not to disclose their use of this form of medication, and both surgeons and anaesthetists often fail to enquire about their use. Anaesthetists and surgeons must be familiar with the effects of herbal medicines and should specifically enquire about the use of herbal medicines during pre-operative assessment. Currently available data suggest that all herbal medicines should be ceased 2 weeks before surgery.

Anesthesia↗

Traditional Chinese herbal medicine and anaesthesia.

An increasing number of people in the western world are using traditional Chinese herbal medicines. There are concerns that these Chinese medicines may contain potentially toxic ingredients and contaminants such as heavy metals. Undeclared conventional western drugs such as the non-steroidal anti-inflammatory and antihistamine drugs, steroids and oral hypoglycaemic agents are frequently added to Chinese herbal medicines. The constituents of the herbal products can cause adverse effects. The anaesthetist should be aware of the potential adverse effects of the herbal products, their contaminants and also of undeclared additives. The potential for drug interactions, coagulopathy and organ dysfunction caused by traditional Chinese herbal medicines has important anaesthetic implications.

Anesthesia↗