Dysrhythmia update: The effect of intermittent heart block on the central venous pressure trace

A prospective study of 71 patients with hyponatraemia was undertaken over an 18-month period in one surgical unit at King Edward VIII Hospital, Durban, to study the incidence and pattern of hyponatraemia. Electrolytes and urea values were measured serially in all patients. Hyponatraemia was defined as a serum sodium level of < 130 mmol/l. The incidence of hyponatraemia was 2.2%, the most common type being normovolaemic hypotonic hyponatraemia. Hyponatraemia was either mild (sodium level 120-130 mmol/l) or moderate (111-120 mmol/l). No patient had severe hyponatraemia (< 110 mmol/l). Hyponatraemia was corrected within 1-6 days using normal saline; in 73% of patients it was corrected within 24 hours. No patient developed neurological symptoms. A mortality rate of 28% was attributed to underlying illness, and hyponatraemia per se was asymptomatic in this study. Aggressive sodium correction was therefore not indicated.     

Severe hyponatraemia: complications and treatment

To observe the incidence of complications in severely hyponatraemic hospitalized patients and relate outcome to rate of correction, all patients admitted to a tertiary referral hospital in New York City, USA or a group of hospitals in Oxford, UK with a sodium < or = 120 mmol/l were studied. Review of the notes and prospective evaluation were used to ascertain cause of hyponatraemia, method of management and outcome. There were 84 episodes in New York and 100 in Oxford, over 9.5 months and one year, respectively; 79% had chronic hyponatraemia ( > 3 days duration). During hyponatraemia, 76% of patients had clouding of consciousness with 11% in coma. Other hyponatraemic complications included long track signs (including hemiparesis) (6.0%), seizures (3.3%), hallucinations (0.5%), tremor (1.0%), intellectual impairment without clouding of consciousness (0.5%), and acute psychosis (0.5%). 4.3% died as a direct result of their electrolyte disturbance. After correction, central pontine myelinolysis (0.5%), post-correction seizures (1.0%), intellectual impairment (2.2%), tremor (0.5%), paraesthesiae (0.5%), and striatal syndrome (0.5%) were observed. Correction of hyponatraemia was started in 158 patients, and the mean maximum rate of correction in 24 h was 8.4 mmol/l (SD 5.6, range 2-42). The maximum rate of correction was higher in those who developed neurological sequelae (12.1 mmol/l/24 h vs. 8.2 mmol/l/24 h; p = 0.0125, t-test, separate variance, two-tail). Neurological sequelae were associated with faster rates of correction, and correction of chronic severe hyponatraemia should be < 10 mmol/l in 24 h.     

Roentgen contrast media, source for AOX-contamination of waste water by hospitals]

A 30-year-old HIV-positive man presented with acute hydrocephalus secondary to tuberculous meningitis, for which an external ventricular drain was inserted. He developed marked natriuresis in the postoperative period, which resulted in acute hyponatraemia (131 to 122 mmol/l) and a contraction of his intravascular volume. A diagnosis of cerebral salt wasting syndrome was made, and he responded to sodium and fluid loading. This case highlights the differentiation of cerebral salt wasting syndrome from the more commonly occurring syndrome of inappropriate anti-diuretic hormone secretion as the aetiology of the hyponatraemia.     

Development of syndrome of inappropriate secretion of antidiuretic hormone during progression of metastatic breast cancer

A patient who developed syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during progression of metastatic breast cancer is described. The classic criteria for SIADH as defined by Bartter and Schwartz were fulfilled and conditions other than malignant disease were excluded as causes of the syndrome. To the knowledge of the authors SIADH has never been reported to develop during the course of malignant disease in a patient with metastatic breast cancer. It should be borne in mind that SIADH may occur in patients with malignant disease and hyponatraemia, even in the absence of small-cell lung cancer, which is the classic tumour type to develop SIADH.     

Hyponatremia as a side effect of serotonin uptake inhibitors

Hyponatraemia is a possible, potentially serious adverse reaction to treatment with selected serotonin re-uptake inhibitors (SSRIs). The article consists in a review of the 27 cases of such reactions that have been reported to the Swedish Medical Products Agency. The data from these reports suggest the risk of hyponatraemia to be particularly manifest during the first few weeks of treatment, and to be greater in women, the elderly, and patients concomitantly treated with diuretics. In the event of vague, non-specific symptoms occurring in conjunction with SSRI treatment, measurement of the serum sodium concentration is recommended.     

Pituitary apoplexy after spinal anaesthesia

We report the case of a previously healthy 51-yr-old male who underwent an uneventful total hip replacement under spinal anaesthesia. His immediate postoperative course was complicated by the development of a severe frontal headache. Initial conservative treatment included oral analgesics and an epidural blood patch. The headache persisted and was followed by progressive vision loss and a right partial third nerve palsy. The patient was almost blind at the time of transfer to our neurosurgical unit. Relevant investigations revealed marked hyponatraemia (serum sodium concentration 122 mmol litre-1) and second-degree heart block (Mobitz I). A CT scan showed a pituitary tumour and confirmed the clinical diagnosis of pituitary apoplexy. Urgent craniotomy was scheduled and a large necrotic pituitary adenoma was excised. The postoperative course was uneventful with return of near normal vision at the time of discharge. Clinicians should consider this diagnosis when focal neurological deficits occur with post-dural puncture headache.     

Urinary tract infections in infants, an insidious clinical picture

Three boys aged 4, 5 and 7 weeks drank poorly, vomited and were lethargic. There were metabolic disorders attributable to a urinary tract infection. Ultrasonography revealed anatomical anomalies. After antibiotic treatment and, if necessary, surgical correction, the patients recovered. Follow-up was uncomplicated except persisting polyuria in one of the patients. A urinary tract infection in young children is difficult to recognise because of the aspecific presenting symptoms. It can cause a severe metabolic disturbance in which hyponatraemia and hyperkalaemia develop (pseudohypoaldosteronism), combined with metabolic acidosis and polyuria. A high alertness for urinary tract infections in young children with these aspecific symptoms is needed as well as metabolic and urologic evaluation.     

Severe hyperkalemia in cardiac patients

Hyperkalaemia with severe myocardial consequence may complicate the treatment of heart failure. In five patients who developed kalaemia ranging from 6.5. to 8.6. mEq/l, the ECG showed altered auriculogram and/or widened QRS, the latter change being associated with ST segment elevation and very large T wave in one case. Such hyperkalaemia cannot be termed iatrogenic, although it is promoted by diuretic-induced hyponatraemia and dehydration. The essential part is played by an aggravation of the haemodynamic status, responsible for acute renal insufficiency with oligoanuria, and by the attendant metabolic acidosis. The correction of this metabolic acidosis promotes diuresis, causing potassium depletion and the rapid regression of electrocardiographic abnormalities. Parenteral alkalinization with sodium bicarbonate, associated with furosemid to prevent sodium overload, instituted in emergency, is the only way to prevent asystole or ventricular fibrillation when kalaemia exceeds 8 mEq/l.     

Fluid and electrolyte homeostasis in the elderly: physiological changes of ageing and clinical consequences

Characteristic of the normal ageing process are changes in the renal, hormonal and thirst regulatory systems involved in the control of sodium and water balance. In the presence of disease or drug use, the ageing changes put the elderly person at increased risk of either sodium retention or loss and of water retention or loss. Clinically, these alterations in water and sodium balance are commonly expressed as either hyponatraemia or hypernatraemia with central nervous system dysfunction as the symptomatic expression. Thus, the impaired homeostasis of the many systems affecting fluid balance in the elderly is readily influenced by many of the disease states and medications which are often present in the elderly with resultant adverse clinical consequences. Awareness of these age-associated circumstances can allow the physician to anticipate the impact of illnesses and drugs and to implement a rational approach to therapeutic intervention and management.     

Clinical and toxicologic aspects of the use of Ecstasy

Methylenedioxymethamphetamine (MDMA, the active compound of ecstacy (XTC) tablets) is a psychoactive amphetamine congener which in humans has a stimulatory effect and enhances feelings of openness and solidarity. MDMA is neurotoxic in animals. It depletes axonal serotonin stores, it inhibits serotonin synthesis by inhibiting tryptophan hydroxylase, and it inhibits the reuptake of serotonin into the neuron. These events lead to destruction of serotonergic axon terminals in animal brain. Selective serotonin reuptake inhibitors protect against the neurotoxic effects of MDMA. Binding of (+)[11C]McN-5652, a selective neuroligand for the serotonin transporter, is decreased in the brains of XTC-users. This indicates that XTC damages serotonergic axon terminals in human brain, also. We strongly advise against the use of XTC as the long-term clinical consequences are not known. In man, somatic life-threatening complications after XTC use include hyperthermia, hyponatraemia and liver failure. Psychiatric complications include psychosis, depression, panic disorder, and impulsive behaviour. The chronic psychosis responds poorly to therapy.     

The effects of two types of exposure on attitudes toward aspects of juvenile delinquency

The essential constituents of a conventional oral rehydration solution (ORS) are sodium, glucose and a bicarbonate precursor. The glucose promotes sodium uptake but because these solutions are isotonic, it is insufficient to sustain calorie requirements. This paper examines the performance of a novel ORS with over three times the conventional glucose concentration, by comparing it with two leading commercial ORSs in calves with induced Escherichia coli diarrhoea. This solution showed greater ability than the current market-leading ORS to repair extracellular fluid and plasma volume and to correct both hyponatraemia and metabolic acidosis, especially in more severely affected calves. In acidotic calves it was more effective in correcting hyperkalaemia, probably by supplying glucose to promote cellular potassium uptake as well as by correcting the acidosis. It therefore appears possible to depart from the traditional isotonic formulations for calf ORSs and gain significant nutritional support while retaining effective rehydration and correction of acid-base and electrolyte disturbances. This seems especially important in young animals where energy deprivation imposes a particular penalty; the use of hypertonic ORSs should not, however, be extended to other species without further research.     

Water balance in elderly people: is there a deficiency of vasopressin?

Since elderly people are prone to develop both hypo- and hyper-natraemia, we have investigated the biochemical and hormonal responses to overnight (9 h) abstinence from fluids and subsequent oral water load (20 ml/kg) in a group of healthy elderly (E) (mean age 68 years) and young (Y) (mean age 28 years) volunteers. The elderly subjects had significantly higher baseline plasma osmolality (E 293.5 +/- 0.5, Y 290.5 +/- 0.8 mOsm/kg, p < 0.05) but lower urinary osmolality (E 508 +/- 47, Y 842 +/- 52 mOsm/kg, p < 0.001) and lower plasma vasopressin (E 0.5 +/- 0.1, Y 2.3 +/- 0.6 pmol/l, p < 0.001) than the young. There was a significant difference in the mode of excretion, particularly maximum free water clearance (E 6.0 +/- 0.6, Y 10.1 +/- 0.8 ml/min) but no difference in the overall ability to excrete the water load (at 4 h E 93 +/- 8%, Y 92 +/- 5%, p > 0.05). The biochemical and hormonal results suggest that the elderly subjects were in a state similar to partial cranial diabetes insipidus which may predispose them to dehydration and hypernatraemia. The reduction in maximum free water clearance may predispose them to hyponatraemia if excess fluid is administered.     

Low sodium levels in serum are associated with subsequent febrile seizures

Fever plays an important role in causing disturbances in fluid and electrolyte balance. Hyponatraemia has been thought to enhance the susceptibility to seizures associated with febrile illnesses in childhood. We have studied serum electrolyte levels in children with simple and complicated febrile convulsions. Sodium levels were lower in those children with complicated convulsions in comparison with those having simple convulsions (136.07 +/- 3.06 mmoll-1, mean +/- SD, n = 42, and 137.62 +/- 2.63 mmoll-1, n = 71, respectively; p < 0.01, Student's t-test). The sodium concentrations were lowest in children with repeated seizures (134.20 +/- 2.30 mmoll-1, n = 15) compared with children having simple (p < 0.01, ANOVA, Duncan's test) or other complicated types of febrile convulsions: focal seizures (137.08 +/- 3.82 mmoll-1, n = 12, p < 0.01), seizures lasting longer than 15 minutes (138.00 +/- 2.45 mmoll-1, n = 5, p < 0.05) and children over 5 years (136.70 +/- 2.06 mmoll-1, n = 10, p < 0.05). Serum potassium levels showed no statistically significant differences between the patient groups. Our results show that hyponatraemia may increase the risk for multiple convulsions during the same febrile illness.     

Resistance to vasopressin action on the kidney in patients with Cushing's disease

OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.     

Newer anticonvulsant drugs: role of pharmacology, drug interactions and adverse reactions in drug choice

In the last few years a number of new anticonvulsants have been introduced into clinical practice mainly as add-on therapy in patients who do not become seizure-free while receiving established anticonvulsants. Up to now, no single drug has been shown to be more effective at controlling seizures of a particular type than another, so other factors such as mechanism of action, pharmacokinetics, dosage regimens or the spectrum of adverse drug reactions and interactions are used when making a choice between one agent and another. The mechanism of action of tiagabine and vigabatrin is very specific; both agents increase gamma-aminobutyric acid (GABA) levels through inhibition of reuptake and catabolism respectively. However, the mechanism of action of gabapentin is unknown and those of felbamate, lamotrigine and topiramate are not sufficiently clarified as yet, and may be multiple. Great advances have been made in improving the pharmacokinetic characteristics of these newer anticonvulsants. Gabapentin and vigabatrin exhibit relatively ideal pharmacokinetic properties as they are not bound to proteins, are excreted mostly unchanged in the urine and show linear pharmacokinetics. Lamotrigine possesses a highly variable elimination half-life depending on the co-medication. Tiagabine is highly protein bound and zonisamide shows nonlinear pharmacokinetics; both these drugs are extensively metabolised. Problematic drug interactions between newer anticonvulsants and other drugs in general occur rarely when these agents are given concomitantly. However, in common with most new drugs, there are very few data on the use of the newer anticonvulsants in women of childbearing age. Studies done so far on interactions with oral contraceptives used low anticonvulsant dosages for a very short time. The newer anticonvulsants elicit adverse reactions that, while not being unique, are particularly associated with that drug. For example, felbamate may cause aplastic anaemia and fulminant liver failure, lamotrigine is prone to cause skin rash, and oxcarbazepine may cause symptomatic hyponatraemia. Topiramate and zonisamide cause kidney stones, and vigabatrin may induce psychiatric syndromes. Although highly diverse in structure and activity, these newer drugs offer new possibilities for treating refractory epilepsy. However, since no single factor can dictate the choice of drug nor predict the success of treatment, prescribing of these rather expensive drugs has to depend upon careful consideration of the aims of treatment, the characteristics of the drug and the needs of the individual patient.     

Forensic autopsies from 1984 to 1993 in Vienna, Austria

In Austria every death is subject to an examination by a medical doctor authorized by the local health authority. If death is suspected to be natural and/or perpetrated by another person, this doctor has to report it to the police. Depending on the investigation results, the examining magistrate in charge demands a judicial autopsy at the Institute of Forensic Medicine. In 1989, 41 murders of old patients by nursing assistants in a Viennese public hospital were disclosed. The main aim of this retrospective study was to determine any change in the demand for forensic autopsies by the Viennese health authority, as well as by the criminal court, after 1989. Furthermore, it was of interest to analyze the reporting practices of medical doctors examining corpses, as well as thr reaction of the criminal court during the study period. After 1989, there was a significant increase of non-judicial and judicial autopsies, performed by Viennese forensic pathologists. In addition, there was a significant increase of reports to the police by coroners as well as by forensic pathologists, paralleled by a higher rate of forensic autopsies demanded by the examining magistrate. This increase of forensic autopsies took place even though the overall rate of deaths in Vienna significantly decreased during the 10-year study period. Thus, the disclosure of 41 murders in the Viennese hospital in 1989 can be assumed as a turning point in the reporting practices of Viennese coroners, as well as the autopsy rate handled by Viennese forensic pathologists.     

Probability of Project Completion Using Stochastic Project Scheduling Simulation

This paper introduces a software, Stochastic Project Scheduling Simulation (SPSS), developed to measure the probability to complete a project in a certain time specified by the user. To deliver a project by a completion date committed to in a contract, a number of activities need to be carried out. The time that an entire project takes to complete and the activities that determine total project duration are always questionable because of the randomness and stochastic nature of the activities’ durations. Predicting a project completion probability is valuable, particularly at the time of bidding. The SPSS finds the longest path in a network and runs the network a number of times specified by the user and calculates the stochastic probability to complete the project in the specified time. The SPSS can be used by a contractor: (1) to predict the probability to deliver the project in a given time frame and (2) to assess its capabilities to meet the contractual requirement before bidding. The SPSS can also be used by a construction owner to quantify and analyze the risks involved in the schedule. The benefits of the tool to researchers are: (1) to solve program evaluation and review technique problems; (2) to complement Monte Carlo simulation by applying the concept of project network modeling and scheduling with probabilistic and stochastic activities via a web based Java Simulation which is operateable over the Internet, and (3) to open a way to compare a project network having different distribution functions.     

Introducing Students to Professional Practice in Civil Engineering

This paper describes a module that was introduced into a civil engineering degree program with the help of professional engineers. The aim was to develop a bridge between the world of learning and professional practice by putting students in the role of consulting engineers working with industry to produce a feasible solution to a real inquiry from a client. The module is placed in context by comparing the goals of accredited civil engineering programs in the United Kingdom and America, by describing how it is linked to the degree program and by explaining the matrix developed to identify the skills the students needed to demonstrate their ability to practice as professional engineers. Details of the module are given with examples of student work and feedback.     

The effects of depression and chronic pain on psychosocial and physical functioning

Ray tracing with a personal computer allows realistic simulation of optical properties of the human eye. Patterns of point sources are used as objects. The path of light rays is calculated between the point source and the retina for a Gullstrand eye model with improved parameters; the normal eye model has a resolution limit close to the natural resolution limit of the human eye. The image formed on the retina is projected back to a screen at the distance of the object so as to simulate image interpretation by the brain. Refractive errors are modeled by a change in eye parameters and corrected by eyeglasses or/and contact lenses or by an artificial intraocular lens. For optic correction the parameters of seeing aids can be fitted automatically by a least-squares routine. The effect of faulty eye correction on image quality is visualized by using a photograph of a realistic scene as an object.     

Complement 5a controls motility of murine microglial cells in vitro via activation of an inhibitory G-protein and the rearrangement of the actin cytoskeleton

Microglial cells respond to most pathological events by rapid transformation from a quiescent to an activated phenotype characterized by increased cytotoxicity and motile activity. To investigate the regulation of microglial motility by different inflammatory mediators, we studied cultured murine microglia by time-lapse video microscopy and a computer-based motility assay. Microglial cells exhibited a high resting motility. The acute application of complement 5a (C5a) immediately induced intense ruffling of microglial membranes followed by lamellipodia extension within few seconds, while formyl-Met-Leu-Phe-OH, bacterial endotoxin (lipopolysaccharide) or inflammatory cytokines did not increase motility. This process was accompanied by a rapid rearrangement of the actin cytoskeleton as demonstrated by labelling with fluorescein isothiocyanate-phalloidin and could be inhibited by cytochalasin B. A GTP-binding protein was involved in the signal cascade, since pertussis toxin inhibited motility and actin assembly in response to C5a. Chemotactic migration in a gradient of C5a was also completely blocked by pertussis toxin and cytochalasin B. The C5a-induced motility reaction was accompanied by an increase in intracellular calcium ([Ca2+]i) as measured by a Fluo-3 based imaging system. Ca2+ transients were, however, not a prerequisite for triggering the increase in motility; motility could be repeatedly evoked by C5a in nominally Ca(2+)-free solution, while Ca2+ signals occurred only upon the first stimulation. Moreover, conditions mimicking intracellular Ca2+ transients, like incubation with thapsigargin or Ca2+ ionophore A23187, were not able to induce any motility reaction, suggesting that Ca2+ transients are not necessary for, but are associated with, microglial motility. Motile activity was shown to be restricted to a defined concentration range of [Ca2+]i as revealed by lowering [Ca2+]i with BAPTA-AM or increasing [Ca2+]i with A23187. Since complement factors are released at pathological sites, this signal cascade could serve to increase motility and to direct microglial cells to the lesioned or damaged area by means of a G-protein-dependent pathway and via the rearrangement of the actin cytoskeleton.