Pre-treatment clinical assessment in head and neck cancer: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides recommendations on the pre-treatment clinical assessment of patients presenting with head and neck cancer. Recommendations • Comorbidity data should be collected as it is important in the analysis of survival, quality of life and functional outcomes after treatment as well as for comparing results of different treatment regimens and different centres. (R) • Patients with hypertension of over 180/110 or associated target organ damage, should have antihypertensive medication started pre-operatively as per British Hypertension Society guidelines. (R) • Rapidly correcting pre-operative hypertension with beta blockade appears to cause higher mortality due to stroke and hypotension and should not be used. (R) • Patients with poorly controlled or unstable ischaemic heart disease should be referred for cardiology assessment pre-operatively. (G) • Patients within one year of drug eluting stents should be discussed with the cardiologist who was responsible for their percutaneous coronary intervention pre-operatively with regard to cessation of antiplatelet medication due to risk of stent thrombosis. (G) • Patients with multiple recent stents should be managed in a centre with access to interventional cardiology. (G) • Surgery after myocardial infarction should be delayed if possible to reduce mortality risk. (R) • Patients with critical aortic stenosis (AS) should be considered for pre-operative intervention. (G) • Clopidogrel should be discontinued 7 days pre-operatively; warfarin should be discontinued 5 days pre-operatively. (R) • Patients with thromboembolic disease or artificial heart valves require heparin therapy to bridge peri-operative warfarin cessation, this should start 2 days after last warfarin dose. (R) • Cardiac drugs other than angotensin-converting enzyme inhibitors and angiotensin II antagonists should be continued including on the day of surgery. (R) • Angotensin-converting enzyme inhibitors and angiotensin II antagonists should be withheld on the day of surgery unless they are for the treatment of heart failure. (R) • Post-operative care in a critical care area should be considered for patients with heart failure or significant diastolic dysfunction. (R) • Patients with respiratory disease should have their peri-operative respiratory failure risk assessed and critical care booked accordingly. (G) • Patients with severe lung disease should be assessed for right heart disease pre-operatively. (G) • Patients with pulmonary hypertension and right heart failure will be at extraordinarily high risk and should have the need for surgery re-evaluated. (G) • Perioperative glucose readings should be kept within 4-12 mmol/l. (R) • Patients with a high HbA1C facing urgent surgery should have their diabetes management assessed by a diabetes specialist. (G) • Insulin-dependent diabetic patients must not omit insulin for more than one missed meal and will therefore require an insulin replacement regime. (R) • Patients taking more than 5 mg of prednisolone daily should have steroid replacement in the peri-operative period. (R) • Consider proton pump therapy for patients taking steroids in the peri-operative phase if they fit higher risk criteria. (R) • Surgery within three months of stroke carries high risk of further stroke and should be delayed if possible. (R) • Patients with rheumatoid arthritis should have flexion/extension views assessed by a senior radiologist pre-operatively. (R) • Patients at risk of post-operative cognitive dysfunction and delirium should be highlighted at pre-operative assessment. (G) • Patients with Parkinson's disease (PD) must have enteral access so drugs can be given intra-operatively. Liaison with a specialist in PD is essential. (R) • Intravenous iron should be considered for anaemia in the urgent head and neck cancer patient. (G) • Preoperative blood transfusion should be avoided where possible. (R) • Where pre-operative transfusion is essential it should be completed 24-48 hours pre-operatively. (R) • An accurate alcohol intake assessment should be completed for all patients. (G) • Patients considered to have a high level of alcohol dependency should be considered for active in-patient withdrawal at least 48 hours pre-operatively in liaison with relevant specialists. (R) • Parenteral B vitamins should be given routinely on admission to alcohol-dependent patients. (R) • Smoking cessation, commenced preferably six weeks before surgery, decreases the incidence of post-operative complications. (R) • Antibiotics are necessary for clean-contaminated head and neck surgery, but unnecessary for clean surgery. (R) • Antibiotics should be administered up to 60 minutes before skin incision, as close to the time of incision as possible. (R) • Antibiotic regimes longer than 24 hours have no additional benefit in clean-contaminated head and neck surgery. (R) • Repeat intra-operative antibiotic dosing should be considered for longer surgeries or where there is major blood loss. (R) • Local antibiotic policies should be developed and adhered to due to local resistance patterns. (G) • Individual assessment for venous thromboembolism (VTE) risk and bleeding risk should occur on admission and be reassessed throughout the patients' stay. (G) • Mechanical prophylaxis for VTE is recommended for all patients with one or more risk factors for VTE. (R) • Patients with additional risk factors of VTE and low bleeding risk should have low molecular weight heparin at prophylactic dose or unfractionated heparin if they have severe renal impairment. (R).

The role of taurine in infant nutrition.

The importance of taurine in the diet of pre-term and term infants has not always been clearly understood and is a topic of interest to students of infant nutrition. Recent evidence indicates that it should be considered one of the "conditionally essential" amino acids in infant nutrition. Plasma values for taurine will fall if infants are fed a taurine-free formula or do not have taurine provided in the TPN solution. Urine taurine values also fall, which is indicative of an attempt by the kidney to conserve taurine. The very-low-birth-weight infant, for a variety of reasons involving the maturation of tubular transport function, cannot maximally conserve taurine by enhancing renal reabsorption and, hence, is potentially at greater risk for taurine depletion than larger pre-term or term infants, and certainly more than older children who have taurine in their diet. Taurine has an important role in fat absorption in pre-term and possibly term infants and in children with cystic fibrosis. Because taurine-conjugated bile acids are better emulsifiers of fat than glycine-conjugated bile acids, the dietary (or TPN) intake has a direct influence on absorption of lipids. Taurine supplementation of formulas or TPN solutions could potentially serve to minimize the brain phospholipid fatty acid composition differences between formula-fed and human milk-fed infants. Taurine appears to have a role in infants, children, and even adults receiving most (> 75%) of their calories from TPN solutions in the prevention of granulation of the retina and electroencephalographic changes. Taurine has also been reported to improve maturation of auditory-evoked responses in pre-term infants, although this point is not fully established. Clearly, taurine is an important osmolyte in the brain and the renal medulla. At these locations, it is a primary factor in the cell volume regulatory process, in which brain or renal cells swell or shrink in response to osmolar changes, but return to their previous volume according to the uptake or release of taurine. While there is a dearth of clinical studies in man concerning this volume regulatory response, studies in cats, rats, and dog kidney cells indicate the protective role of taurine in hyperosmolar stress. The infant depleted of taurine may not be able to respond to hyper- or hyponatremic stress without massive changes in neuronal volume, which has obvious clinical significance. The fact that the brain content of taurine is very high at birth and falls with maturation may be a protective feature, or compensation for renal immaturity Defining an amino acid as "conditionally essential" requires that deficiency result in a clinical consequence or consequences which can be reversed by supplementation. In pre-term and term infants, taurine insufficiency results in impaired fat absorption, bile acid secretion, retinal function, and hepatic function, all of which can be reversed by taurine supplementation. Therefore, this small beta-amino acid, taurine, is indeed conditionally essential.

Effect of K+- and kainate-mediated depolarization on survival and functional maturation of GABAergic and glutamatergic neurons in cultures of dissociated mouse cerebellum.

The effect of the depolarizing agents, an elevated potassium concentration (25 mM) or kainic acid (50 microM) on neuronal survival and differentiation was investigated in cultures of dissociated neurons from cerebella of 7-day-old mice. When maintained in the presence of an antimitotic agent such cultures consist primarily of glutamatergic and GABAergic neurons. Cell survival was monitored by measurement of DNA, and differentiation by determining uptake and depolarization coupled release of glutamate (D-aspartate as label) and GABA. The depolarizing agents were added separately or together either from the start of the culture period (7-8 days) or at day 5 in culture. The main findings are that K+ depolarization is important for differentiation of glutamatergic neurons but not for GABAergic neurons. This depolarizing signal is important during the early phase of development in culture. For glutamatergic neurons, kainate may replace K+ as a depolarizing signal whereas in case of the GABAergic neurons, kainate was toxic particularly during the late phase of development. It was further observed that the glutamatergic neurons when maintained in a medium with 5 mM K+ during the first 5 days in culture became sensitive to kainate toxicity when this amino acid was added at day 5. This was not the case when the medium contained 25 mM K+ from the start of the culture period.

Dietary beta-alanine results in taurine depletion and cerebellar damage in adult cats.

We have used the taurine analogue, beta-alanine, to perturb the taurine concentrations in taurine-supplemented and taurine-deprived adult cats. By using 5% beta-alanine in the drinking water for 20 weeks, both groups of cats had greatly reduced brain taurine concentrations. Taurine-supplemented cat brain accumulated relatively small amounts of beta-alanine whereas taurine-deprived cats accumulated large amounts of beta-alanine. The cerebellum of cats treated with beta-alanine had a number of pathological changes compared with similar cats drinking water alone. The changes were more severe in the taurine-deprived cats, and included reduced numbers of granule and Purkinje cells, with many of those remaining appearing pyknotic and dying. Long swollen fibers were seen in the white matter, resembling Rosenthal fibers described in some human cerebellar diseases. There was also prominent gliosis. Using antibodies to beta-alanine and taurine, beta-alanine was localized in Purkinje cell soma and dendrites, in Golgi II cells, and in some granule cells, especially in taurine-deprived cats treated with beta-alanine. Taurine appears to have been virtually eliminated from Purkinje and granule cells, and concentrated in Golgi II cells and glia. We conclude that beta-alanine is responsible for these neurotoxic pathological changes.

Taurine: A therapeutic agent in experimental kidney disease.

Taurine is an abundant free amino acid in the plasma and cytosol. The kidney plays a pivotal role in maintaining taurine balance. Immunohistochemical studies reveal a unique localization pattern of the amino acid along the nephron. Taurine acts as an antioxidant in a variety ofin vitro andin vivo systems. It prevents lipid peroxidation of glomerular mesangial cells and renal tubular epithelial cells exposed to high glucose or hypoxic culture conditions. Dietary taurine supplementation ameliorates experimental renal disease including models of refractory nephrotic syndrome and diabetic nephropathy. The beneficial effects of taurine are mediated by its antioxidant action. It does not attenuate ischemic or nephrotoxic acute renal failure or chronic renal failure due to sub-total ablation of kidney mass. Additional work is required to fully explain the scope and mechanism of action of taurine as a renoprotective agent in experimental kidney disease. Clinical trials are warranted to determine the usefulness of this amino acid as an adjunctive treatment of progressive glomerular disease and diabetic nephropathy.

Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats.

We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.

Taurine in pediatric nutrition.

The past 20 years have seen the status of taurine change from an end product of methionine and cysteine metabolism and substance conjugated to bile acids to that of an important, and sometimes essential, nutrient. It is now added to most synthetic human infant formulas and pediatric parenteral solutions throughout the world. This article describes the research that led to this end.

Altered GABA distribution in hamster brain is an early molecular consequence of infection by scrapie prions.

Antibodies specific for GABA, glutamate and taurine were used to study the distribution of these amino acid neurotransmitters during the progression of scrapie in hamsters. Immunohistochemical distribution of glutamate and taurine were unaffected in scrapie hamsters compared with controls, but the distribution of GABA was altered by 21 days after inoculation. We found both a greater number of neurons showing GABA-like immunoreactivity and more intense staining in those neurons in scrapie-inoculated hamster brains, particularly in the hippocampus, inferior colliculus, frontal cortex and cerebellum. The overall concentrations of aspartate, GABA, glutamate and taurine, measured in seven different brain regions by PITC-amino acid analysis, were not significantly different between normal and scrapie-affected hamsters. The subtle alteration in GABA metabolism detected in this scrapie model suggests that PrPSc interacts directly with a component of the GABA system.

Excitatory amino acid receptors in membranes from cultured human retinal pigment epithelium.

The presence of specific, saturable receptor sites for excitatory amino acids (EAA) in membranes from cultured human retinal pigment epithelium (RPE) was established through the binding of [3H]L-glutamate (L-Glu). The age of the donors ranged from 6 days to 33 years. The affinity of the binding (KB) sites was between 1.2 and 1.5 microM, and did not change with the age of the donor, whereas the Bmax was slightly increased (8.6 to 13.0 pmol/mg) in membranes from the 33 year-old compared to the 29 day-old donor. The efficacy profile of agonists and antagonists acting at EAA receptors for displacing [3H]L-Glu was L-Glu = L-Aspartate > 2-amino-4-phosphonovalerate (AP5) > N-methyl-D-Aspartate (NMDA) > 1-aminocyclopentane-1,3 dicarboxylate (trans-ACPD) > 2-amino-3-phosphonopropionate (AP3). These data suggest the presence of either an NMDA-receptor sensitive to the metabotropic agonist trans-ACPD or alternatively, the presence of two different populations of receptors with similar affinity for the agonist: NMDA and metabotropic. Glycine highly stimulated Glu-binding; this effect was inversely related to the age of the donor. Taurine and to a lesser extent GABA, mimicked this effect. Stimulation by glycine was dose-dependent, insensitive to strychnine and 80% inhibited by 7-chlorokynurenate. This effect was also present in human RPE-derived fibroblasts, human scleral fibroblasts and the human lymphoblastoid cell line NB76, all continuously dividing cells. The results further support the possibility of the participation of EAA receptors in the regulation of phagocytosis in RPE.

Retinal morphology and visual pigment levels in 6- and 12-month-old rhesus monkeys fed a taurine-free human infant formula.

Rhesus monkey infants were raised from birth until 6 or 12 months of age on a taurine-free soy protein-based human infant formula or on the same formula supplemented with taurine. An additional group received taurine-free formula until 6 months and then the supplemented diet from 6 until 12 months. The densities of rod and cone visual pigments were measured by fundus reflectometry at 6 and 12 months, and retinal morphology was then examined by light and electron microscopy. The densities of rhodopsin, measured in the near periphery after a white bleach, and of cone pigment, measured in the macula after a red bleach, were significantly reduced in the taurine-deprived monkeys at 6 months but not at 12 months. The retinas of 6-month-old taurine-deprived infants showed degenerative morphological changes in photoreceptors, particularly in cones in the foveal region, which were somewhat less severe than those seen in a previous study at 3 months of age. The prevalence and degree of these abnormalities continued to decrease with age in taurine-deprived animals, but changes persisted in some animals at 12 months. Recovery was more complete in monkeys reversed to the supplemented diet from 6 to 12 months. Thus, monkey infants are dependent on dietary taurine to maintain normal retinal structure until at least 6 months of age; the effects of taurine deprivation regress spontaneously but incompletely by 12 months.