A multicentre prospective observational study of the prevalence and glycaemic control of diabetes mellitus in adult non-cardiac elective surgical patients in hospitals in Western Cape Province, South Africa.

BACKGROUND: Diabetes mellitus (DM) is a common condition. The high burden of undiagnosed DM and a lack of large population studies make accurate prevalence estimations difficult, especially in the surgical environment. Furthermore, poorly controlled DM is associated with an increased risk of perioperative complications and mortality. OBJECTIVES: The primary objective was to establish the prevalence of DM in elective adult non-cardiac, non-obstetric surgical patients in hospitals in Western Cape Province, South Africa. The secondary objectives were to assess the glycaemic control and compliance with treatment of known diabetics. METHODS: A 5-day multicentre, prospective observational study was performed at six government-funded hospitals in the Western Cape. Screening for DM was done using finger-prick capillary blood glucose (CBG) testing. Patients found to have a CBG ≥6.5 mmol/L had their glycated haemoglobin (HbA1c) level measured. DM was diagnosed based on the Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) diagnostic criteria. Patients known to have DM had their HbA1cmeasured and completed a Morisky Medication Adherence Scale (MMAS-4) questionnaire to assess glycaemic control and compliance with treatment. RESULTS: Of the 379 participants, 61 were known diabetics (16.2%; 95% confidence interval (CI) 12.4 - 19.8). After exclusion of 8 patients with incomplete results, a new diagnosis of DM was made in 5/310 patients (1.6%; 95% CI 0.2 - 3.0). The overall prevalence of DM was 17.8% (66/371; 95% CI 13.9 - 21.7). HbA1c results were available for 57 (93.4%) of the 61 known diabetics. Of these, 27 (47.4%; 95% CI 34.4 - 60.3) had an HbA1c level ≥8.5% and 14 (24.6%; 95% CI 13.4 - 35.8) had a level ≤7%. Based on positive responses to two or more questions on the MMAS-4 questionnaire, 12/60 participants (20.0%) were deemed non-compliant. CONCLUSIONS: There is a low rate of undiagnosed DM in our elective surgical population, but in a high proportion of patients with DM the condition is poorly controlled. Poorly controlled DM is known to increase postoperative complications and is likely to increase the burden of perioperative care. Resources should be focused on improvement of long-term glycaemic control in patients presenting for elective surgery.

A multicentre prospective observational study of the prevalence of preoperative anaemia and iron deficiency in adult elective surgical patients in hospitals in Western Cape Province, South Africa.

BACKGROUND: Preoperative anaemia has been shown to be an independent risk factor for postoperative morbidity and mortality. Iron deficiency is the leading cause of anaemia globally. There are limited data describing the burden of perioperative anaemia and the relative contribution of iron deficiency in South Africa (SA). OBJECTIVES: To determine the prevalence and severity of preoperative anaemia in adults presenting for elective surgery in Western Cape Province, SA, and to investigate the contribution of iron deficiency as a cause of the anaemia. For this purpose, an investigative protocol from a recent consensus statement on the management of perioperative anaemia was applied. METHODS: We performed a prospective, observational study in adult patients presenting for elective non-cardiac, non-obstetric surgery over a 5-day period at six Western Cape government-funded hospitals. The World Health Organization patient classification was applied, and patients with anaemia were investigated for iron deficiency. RESULTS: The prevalence of preoperative anaemia was 28% (105/375; 95% confidence interval (CI) 23.5 - 32.5); 55/105 patients (52%) had moderate and 11/105 (11%) severe anaemia. Iron deficiency was the cause of anaemia in 37% (32/87; 95% CI 26.6 - 46.9), but only 9% of iron-deficient patients received iron supplementation prior to surgery. CONCLUSIONS: Preoperative anaemia was common in this study, and more than half of the affected patients had moderate to severe anaemia. Iron deficiency was responsible for almost 40% of cases. Iron supplementation was under-utilised in the preoperative period as a means of increasing haemoglobin. The introduction of system-wide policies would empower perioperative physicians to mitigate the risk associated with preoperative anaemia in the Western Cape.

Radiological evaluation of tube depth and complications of prehospital endotracheal intubation in pediatric trauma: a descriptive study.

PURPOSE: Pediatric prehospital endotracheal intubation (PHETI) is a difficult and rarely performed procedure that remains the gold standard for prehospital airway management when ventilation and/or anesthesia is required, but high complications rates, including malposition continue to concern. We reviewed the experience in our institution of pediatric intubations with particular emphasis on the position of the endotracheal tube (ETT) tip within the trachea and related complications. METHOD: Intubated pediatric patients presenting directly from the scene to our level 1 trauma center, between 2006 and 2014, were included in our study. Patient records and radiographs were retrospectively reviewed to identify the ETT tip-to-carina distance and possible intubation-related complications. ETT tips identified beyond the carina on radiographs or by clinical diagnosis were defined as misplaced. Because head movement causes a significant ETT movement within the trachea, which is age related, we also defined ETT tip placement (1) less than 2 cm above the carina in children younger than 8 and (2) less than 3 cm above the carina in children 8 years or older as "near miss" intubations. RESULTS: From a total of 34 cases, ETT misplacement was identified in seven cases. Diagnosis was made radiologically in five cases and clinically in two cases. Four of these patients had left lung atelectasis due to tube misplacement. Tube thoracotomy was performed in two of these patients without concurrent evidence of chest injury. "Near miss" intubations accounted for 7/9 and 9/25 in children <8 years and ≥8 years old, respectively, totaling 16/34, with two of these leading to late displacements. CONCLUSIONS: Pediatric endotracheal tube intubation carries a high rate of tube malposition and left lung atelectasis in our experience of pediatric trauma patients, with less than a third of ETTs placed in a safe position.

Etiology, Diagnosis and Treatment of Tendinous Knee Extensor Mechanism Injuries.

BACKGROUND AND AIMS: Quadriceps and patella tendon ruptures are uncommon injuries often resulting from minor trauma typically consisting of an eccentric contraction of the quadriceps muscle. Since rupture of a healthy tendon is very rare, such injuries usually represent the end stage of a long process of chronic tendon degeneration and overuse. This review aims to give an overview of the current understanding of the pathophysiology, diagnostic principles, and recommended treatment protocols as supported by the literature and institutional experience. MATERIAL AND METHODS: A non-systematic review of the current literature on the subject was conducted and reflected against the current practice in our level 1 trauma center. RESULTS AND CONCLUSION: Risk factors for patella and quadriceps tendon rupture include increasing age, repetitive micro-trauma, genetic predisposition, and systemic diseases, as well as certain medications. Diagnosis is based on history and clinical findings, but can be complemented by ultrasound or magnetic resonance imaging. Accurate diagnosis at an early stage is of utmost importance since delay in surgical repair of over 3 weeks results in significantly poorer outcomes. Operative treatment of acute ruptures yields good clinical results with low complication rates. Use of longitudinal transpatellar drill holes is the operative method of choice in the majority of acute cases. In chronic ruptures, tendon augmentation with auto- or allograft should be considered. Postoperative treatment protocols in the literature range from early mobilization with full weight bearing to cast immobilization for up to 12 weeks. Respecting the biology of tendon healing, we advocate the use of a removable knee splint or orthotic with protected full weight bearing and limited passive mobilization for 6 weeks.

Effect of dexamethasone on zinc transport in rat hepatocytes in primary culture.

Incubation of hepatocytes in medium supplemented with 1 microM dexamethasone and 15 or 30 microM ZnCl2 for 24 h resulted in increased intracellular Zn and metallothionein levels. There were a positive correlation between the Zn and metallothionein concentrations. Initial rates of 65Zn influx from balanced salt solutions containing albumin and ZnCl2 to give known free Zn2+ concentrations were measured over 10 min. At 1.6 nM free Zn2+ the influx rate was the same in control and dexamethasone-treated cultures, but at 18 nM free Zn2+ there was an increased rate of influx after dexamethasone treatment. Measurements of 65Zn efflux were quite hard to interpret, because of the existence of at least two intracellular Zn pools, a fast-exchanging and a slow-exchanging pool. The amount of Zn in the fast-exchanging pool appeared to increase as the external free Zn2+ concentration was increased, while the amount in the slow-exchanging pool increased on pre-treatment with Zn and dexamethasone. The fractional efflux of 65Zn from the fast-exchanging pool appeared to increase with the pool size, implying that the rate of Zn efflux increases faster than the concentration of Zn2+ in that pool.

Active transport of lead by human red blood cells.

Human red cells suspended in lead-citrate buffers (2.6 microM Pb2+) take up much less Pb than predicted from studies of equilibrium binding of Pb to haemolysates. Pb uptake is increased by ATP depletion, or by loading at 0 degrees C. Tracer studies with 203Pb indicate that the low uptake at 37 degrees C in the presence of substrate is not due to membrane impermeability to Pb. Cold-loaded cells extrude Pb against a concentration gradient at 37 degrees C when glucose is present. These results suggest that the cellular loading of Pb is dependent on the balance between an inward leak and an outward pump. The extrusion of Pb from the cells is possibly brought by the Ca pump.

The internal carotid artery has a sleeve of increased innervation density within the cavernous sinus in monkeys.

The numerical density of nerve terminals of the internal carotid artery was measured using interrupted serial sections and compared with densities sampled from the major cerebral arteries of cynomolgus and rhesus monkeys. In its course through the carotid canal and the foramen lacerum the artery received few terminals. Nerve terminal density increased substantially within the cavernous sinus in 13 of 19 animals, reaching a peak shortly before emerging to join the circle of Willis. The density dropped rapidly on leaving the sinus. The increase was present in both species and rose to a mean nerve terminal density at least ten times that of any other artery measured. In 6 monkeys terminal incidence was unchanged through the sinus. The possible relevance of the nerve terminal sleeve to cerebral vasodynamics and to vascular head pain is discussed.

Lead-calcium interactions in cellular lead toxicity.

The interaction of Pb and Ca with cellular sites depends upon the concentration of free ions present (Pb2+, Ca2+). The ability of Pb2+ to form complexes with simple anions such as Cl- and OH-, the formation of precipitates such as Pb(OH)2 and Pb3(PO4)2, and the ubiquity of Pb as a contaminant in laboratory reagents implies that particular care is needed in order to define the Pb2+ concentration of a solution. The free Pb2+ concentration may be controlled with Pb2+ buffers, and measured with a Pb2+ selective electrode, a fluorescent dye, fura-2, or an NMR indicator, 19F-BAPTA. Pb(2+)-Ca2+ interactions occur in three main situations at the cellular level. Pb2+ and Ca2+ compete at the plasma membrane for transport systems which effect their entry or exit, such as Ca2+ channels, and the Ca2+ pump. Intracellular Ca2+ is buffered to around 10(-7) M by proteins, endoplasmic reticulum and mitochondria. Pb2+ disturbs intracellular Ca2+ homeostasis. Ca(2+)-Pb2+ interactions at mitochondria have been described, but other mechanisms have not yet been explored. Increases in intracellular [Ca2+] act as a signal (or second messenger). Pb2+ interacts with a number of Ca(2+)-dependent effector mechanisms, such as calmodulin (a Ca2+ receptor protein which couples to several enzymes e.g., phosphodiesterase, protein kinases), protein kinase C, Ca(2+)-dependent K+ channels in the plasma membrane and neurotransmitter release. The actions of Pb2+ on neurotransmission may be relevant to Pb(2+)-induced human neuropathy and encephalopathy.

Measurement of free Zn2+ ion concentration with the fluorescent probe mag-fura-2 (furaptra).

The fluorescent probe mag-fura-2, previously used to measure [Mg2+], can also be used to measure [Zn2+]. The peak in the excitation spectrum occurs at 323 nm for Zn2+, compared with 335 nm for Ca2+ and Mg2+. This allows simultaneous measurements of [Zn2+] and either [Ca2+] or [Mg2+], by using 3 excitation wavelengths. The dissociation constant for Zn2+ is 20 nM at pH 7.0-7.8, ionic strength 0.15 and 37 degrees C. This allows [Zn2+] to be measured in the range from 0.5 nM to 1 microM. Mag-fura-2 was used to measure [Zn2+] in Zn2+/albumin and Zn2+/histidine mixtures in a physiological buffer at 37 degrees C and pH 7.4. The data obtained enable one to formulate Zn(2+)-buffers for the 1 to 100 nM Zn2+ range.

Task conflict and relationship conflict in top management teams: the pivotal role of intragroup trust.

Task conflict is usually associated with effective decisions, and relationship conflict is associated with poor decisions. The 2 conflict types are typically correlated in ongoing groups, however, which creates a prescriptive dilemma. Three explanations might account for this relationship--misattribution of task conflict as relationship conflict, harsh task conflict tactics triggering relationship conflict, and misattribution of relationship conflict as task conflict. The authors found that intragroup trust moderates the relationship between task conflict and relationship conflict in 70 top management teams. This result supports the "misattribution of task conflict" explanation. The authors also found a weak effect that is consistent with the argument that tactical choices drive the association between the 2 conflict types. We infer that trust is a key to gaining the benefits of task conflict without suffering the costs of relationship conflict.

Influence of Zn2+ and water on the transport properties of a pyrrolidinium dicyanamide ionic liquid.

In order to expand our understanding of a potential zinc-based battery electrolyte, we have characterized the physical and transport properties of the ionic liquid (IL) 1-butyl-1-methylpyrrolidinium dicyanamide ([C4mpyr][dca]) containing various levels of both Zn(2+) and H2O. Detailed measurements of density, viscosity, conductivity, and individual anion and cation diffusion coefficients using pulsed-field-gradient (PFG) NMR combined with NMR chemical shifts and spin-lattice relaxation (T1) NMR experiments provide insights into the motion and chemical environment of all molecular species. We find that the various techniques for probing ion transport and dynamics form a coherent picture as a function of electrolyte composition. Zn(2+) addition causes a moderate reduction in the self-diffusion of the IL anion and cation, whereas the addition of H2O increases ion mobility by increasing the liquid's overall fluidity. Temperature-dependent (13)C T1 experiments of the dca carbon analyzed using Bloembergen-Purcell-Pound fits show monotonic slowing of anion dynamics with Zn(2+) addition, suggesting increased Zn(2+)/dca(-) association. T1 experiments show minimal change in the spin-lattice relaxation of cation or anion upon H2O addition, suggesting that H2O is playing no significant role in Zn(2+) speciation. Finally, we employ a novel electrophoretic NMR technique to directly determine the electrophoretic mobility of the C4mpyr cation, which we discuss in the context of impedance-based conductivity measurements.

The role of anion transport in the passive movement of lead across the human red cell membrane.

Passive Pb transport across the red cell membrane has been studied by measuring Pb uptake from Pb-buffered solutions into resealed ghosts containing EGTA. Over 90% of Pb uptake occurs by a pathway which is inhibited by drugs which block anion transport. The order of effectiveness is 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS) greater than phloretin greater than furosemide and bumetanide. Ouabain and cytochalasin B are ineffective. This implicates the anion-exchange mechanism in Pb uptake. The rate of Pb uptake by this route is directly proportional to external Pb2+ and HCO3- concentrations, and inversely proportional to the H+ concentration. These findings suggest that Pb transport depends on the formation of PbCO3 in solution. Pb transport depends upon the presence of a second anion. In the presence of HCO3-, the rate is stimulated in the order ClO4- less than NO3- and CH3CO2- less than F- less than Cl- less than Br- less than I-. The temperature dependence of Pb uptake is similar to that of HCO3-(-)Cl- exchange. Changes in membrane potential appear to influence Pb transport. The effects are small and somewhat variable, but in general a negative internal potential accelerates uptake and reduces exit. A positive internal potential reduces uptake and accelerates exit. These results suggest that Pb is transported on the anion exchanger. Exchange of PbCO3 for a monovalent anion best fits the experimental data, although transport of a ternary PbCO3(-)anion- complex is a possibility.

Influence of lead ions on cation permeability in human red cell ghosts.

Intracellular Pb2+ ions can replace Ca2+ ions in stimulating the Ca-dependent K permeability of human red blood cells. In metabolically depleted resealed ghosts, the threshold for stimulation of 86Rb efflux by internal Pb2+ is around 5 X 10(-10) M, and stimulation is half-maximal at about 2 X 10(-9) M, and maximal at 10(-8) M Pb2+. There is no effect on 22Na efflux in this concentration range. 86Rb efflux is antagonized by internal Mg2+ ions, and by the channel-blocking drugs quinidine and diS-C2(5), as observed for the Ca-dependent K permeability in red cells. In ghosts containing EDTA, which prevents any internal effects of Pb2+ ions, external Pb2+ increases both 22Na and 86Rb permeability when its concentration exceeds 6 X 10(-7) M. This effect is seemingly unrelated to the Ca-dependent K permeability. This work makes extensive use of Pb2+ ion buffers, and gives information about their preparation and properties.

The preparation of human red cell ghosts containing calcium buffers.

1. Ca buffers may be introduced into human red cells by reversible haemolysis. The resealed ghosts retain Ca and chelating anions in the same ratio as in the haemolysing solution, enabling the intracellular Ca2+ concentration to be calculated simply. 2. The passive permeability of the ghosts to Na and Cl is unaffected by intracellular Ca2+ concentrations in the 10(-8)-10(-4) M range, whereas the K permeability is greatly increased at concentrations above 10(-7) M. 3. These preparations enable Ca-dependent K movements to be studied under stable conditions. When the ghosts contain about 5 X 10(-6) M-Ca2+, over 96% of K transport occurs via the Ca-sensitive route.

Calcium-dependent potassium exchange in human red cell ghosts.

1. The properties of the Ca-dependent K transport system of human red cell ghosts have been examined under equilibrium exchange conditions. 2. K transport is stimulated half-maximally by about 0-4muM-Ca2i+ or 5muM-Sr2i+, but much higher concentrations of Ba2i+ give only slight stimulation. Mg is a weak antagonist to Ca. 3. The free Ca2+ concentration in human red cells is estimated to be below 0-25muM. 4. The curve relating the rate of K transport to the intracellular Ca2+ concentration is complicated and suggests that internal Ca acts at three or more sites. 5. K, Rb and possibly Cs ions are transported by the Ca-dependent system. Under comparable conditions the relative rates are 1(K):1-5(Rb): less than 0-05(Cs). 6. No Ca-dependent transport of Na, Li or choline could be detected. If Na is transported, it must be at less than 1/40 of the rate of K. 7. The rate of K transport is almost linearly related to the K concentration in the 0-200 mM range, but the curve is sigmoid close to the origin. 8. Intracellular, but not extracellular Na inhibits K transport, in a way that suggests competition with K at more than one site. 9. These results suggest that the transport system has a complex mechanism.

Intracellular free zinc and zinc buffering in human red blood cells.

Zn2+ has been allowed to equilibrate across the red cell membrane using two agents that increase membrane permeability to this ion: the ionophore A23187 and the specific carrier ethylmaltol. Extracellular free Zn2+ was controlled with EGTA (1,2-di(2-aminoethoxy)ethane-NNN'N'tetra-acetic acid] buffers, except in the case of ethylmaltol, which itself acts as a buffer. Measurement of cellular zinc content at different levels of free Zn2+ facilitated the study of intracellular Zn2+ binding. It was also possible to estimate intracellular free Zn2+ concentration in untreated cells using a "null-point" technique. Intracellular zinc was found to consist of an inexchangeable component of about 129 mumol/10(13) cells and an exchangeable component of 6.7 +/- 1.5 mumol/10(13) cells, with a free concentration of about 2.4 x 10(-11) M. The main component of Zn2+ buffering is hemoglobin, with a dissociation constant of about 2 x 10(-8) M.

Calcium-dependent zinc efflux in human red blood cells.

Zinc efflux from human red blood cells is largely brought about by a saturable mechanism that depends upon extracellular Ca2+ ions. It has a Vmax of about 35 mumol/10(13) cells hr, a Km for external Ca2+ of 1 x 10(-4) M, and a Km for internal Zn2+ of 1 x 10(-9) M. External Zn2+ inhibits with a K0.5 of 3 x 10(-6) M. Sr2+ is a substitute for external Ca2+, but changes in monovalent anions or cations have little effect on the Zn2+ efflux mechanism. It is unaffected by most inhibitors of red cell transport systems, although amiloride and D-600 (methoxyverapamil, a Ca2+ channel blocker) are weakly inhibitory. The transport is capable of bringing about the net efflux of Zn2+, against an electrochemical gradient, provided Ca2+ is present externally. This suggests it may be a Zn2+:Ca2+ exchange, which would be able to catalyze the uphill movement of Zn2+ at the expense of an inward Ca2+ gradient, which is itself maintained by the Ca2+ pump.

The affinity of human erythrocyte porphobilinogen synthase for Zn2+ and Pb2+.

Porphobilinogen synthase activity has been measured in human erythrocyte lysates supplemented with metal-ion buffers to control free Zn2+ and Pb2+ concentrations. The enzyme is activated by Zn2+ with a Km of 1.6 pM and inhibited by Pb2+ with a Ki of 0.07 pM. Pb2+ and Zn2+ appear to compete for a single metal-binding site. The half-time for loss of Zn2+ from the active site, or replacement of Pb2+ by Zn2+, were in the 10-20-min range at 37 degrees C. Zn2+ did not affect the affinity for the substrate 5-aminolevulinate, but Pb2+ reduced it non-competitively. All the experiments were conducted with a blood sample of the common 1-1 phenotype [Astrin, K. H., Bishop, D. F., Wetmur, J. G., Kaul, B., Davidow, B. & Desnick, R. J. (1987) Ann. NY Acad. Sci. 514, 23-29].