Effects of therapeutic hypothermia on intracranial pressure and outcome in patients with severe head injury

OBJECTIVE: Therapeutic hypothermia may improve outcome in patients with severe head injury, but clinical studies have produced conflicting results. We hypothesised that the severe side effects of artificial cooling might have masked the positive effects in earlier studies, and we treated a large group of patients with severe head injury with hypothermia using a strict protocol to prevent the occurrence of cooling-induced side effects. DESIGN: Prospective clinical trial. SETTING: University teaching hospital. PATIENTS: Hundred thirty-six consecutive patients admitted to our hospital with severe head injury (Glasgow Coma Scale (GCS) < or =8). MEASUREMENTS AND RESULTS: Patients included are the 136 patients with a GCS of 8 or less on admission in whom intracranial pressure (ICP) remained above 20 mmHg in spite of therapy according to a step-up protocol. Those who responded to the last step of our protocol (barbiturate coma) constituted the control group (n=72). Those who did not respond to barbiturate coma (n=64) were treated with moderate hypothermia (32-34 degrees C). Average APACHE II scores were higher (28.9+/-14.4 vs 25.2+/-12.1, p<0.01) and average GCS at admission slightly lower (5.37+/-1.8 vs 5.9+/-2.1, p<0.05) in the hypothermia group, indicating greater severity of illness and more severe neurological injury. Predicted mortality was 86% for the hypothermia group versus 80% in controls (p<0.01). Actual mortality rates were significantly lower: 62% versus 72%; the difference in mortality between hypothermic patients and controls was significant (p<0.05). The number of patients with good neurological outcome was also higher in the hypothermia group: 15.7% versus 9.7% for hypothermic patients versus controls, respectively (p<0.02). These differences were explained almost entirely by the subgroup of patients with GCS of 5 or 6 at admission (mortality 52% vs 76%, p<0.01; good neurological outcome 29% vs 8%, p<0.01). CONCLUSIONS: Artificial cooling can significantly improve survival and neurological outcome in patients with severe head injury when used in a protocol with great attention to the prevention of side effects. Because there is likely to have been bias against the hypothermia group in this study, the positive effects of hypothermia might even have been underestimated. In addition, our results confirm the value of therapeutic hypothermia in treating refractory intracranial hypertension.     

Piperacillin-induced magnesium and potassium loss in intensive care unit patients

OBJECTIVE: Broad spectrum penicillins such as piperacillin are used extensively in the intensive care unit (ICU) because of their wide bacterial spectrum and low level of toxicity. Although some cases of interstitial nephritis induced by piperacillin have been reported, this problem is thought to be rare. However, in view of the large number of other risk factors for renal disorders that are frequently present in ICU patients, we speculated that ICU patients might be more at risk for renal side effects. We therefore decided to measure serum electrolyte levels in patients before and after piperacillin administration. DESIGN: Prospective observational study. SETTING: University teaching hospital. PATIENTS AND PARTICIPANTS: Forty-three consecutive patients with normal renal function treated with piperacillin; 40 patients treated with other antibiotics. RESULTS: Serum levels of magnesium (Mg), potassium (K) and, to a lesser degree, calcium (Ca) decreased significantly in patients treated with piperacillin, but not in patients treated with other antibiotics ( p<0.01). This decrease was especially pronounced in a subgroup of patients concurrently treated with furosemide. CONCLUSIONS: We conclude that treatment with piperacillin may cause or aggravate electrolyte disorders and tubular dysfunction in ICU patients even when serum creatinine levels remain normal.     

A randomised controlled clinical trial on the additional effect of hypnosis in a comprehensive treatment programme for in-patients with conversion disorder of the motor type

BACKGROUND: The primary aim of this study was threefold: (1) to examine the additional effects of hypnosis aimed at symptom reduction, using symptom-oriented and expression- and insight-oriented techniques in a comprehensive clinical treatment programme for in-patients with a persistent conversion disorder of the motor type; (2) to assess whether the level of hypnotisability was predictive of treatment outcome, and (3) to explore the efficacy of the total clinical treatment programme. METHODS: The study population consisted of 45 in-patients between 18 and 65 years of age meeting the DSM-III-R criteria for conversion disorder of the motor type or somatisation disorder with motor conversion symptoms. A randomised controlled clinical trial was undertaken. The primary outcome measures were the Video Rating Scale for Motor Conversion Symptoms, the D(isabilities) code items from the International Classification of Impairments, Disabilities and Handicaps and the Symptom Checklist-90. Measures of the credibility of treatment and patient expectations of treatment outcome were used as manipulation checks. Hypnotisability was measured using the Stanford Hypnotic Clinical Scale. RESULTS: Significant treatment results for all outcome measures were found for the total sample. These effects proved to be clinically significant. The use of hypnosis had no additional effect on treatment outcome. Hypnotisability was not predictive of treatment outcome. CONCLUSION: A comprehensive treatment programme, either with or without hypnosis, can be worthwhile for patients with long-standing conversion symptoms.     

Two-part implants inserted in a one-stage or a two-stage procedure. A prospective comparative study

OBJECTIVE: The aim of this study was to evaluate the feasibility of using a two-part implant system in a one-stage procedure and to monitor the microflora in the peri-implant area in relation to clinical and radiographic outcome. MATERIAL AND METHODS: After randomisation, 40 edentulous patients (Cawood & Howell class V-VI) received two IMZ implants in the anterior mandible inserted by either a one-stage (n = 20) or a two-stage (n = 20) surgical procedure for overdenture treatment. A standardised clinical and radiographic evaluation was performed after denture insertion as well as 6 and 12 months thereafter. Twelve months after loading, peri-implant samples were collected and analysed for the presence of putative periodontal pathogens using culture technique. RESULTS: No striking differences were found between the two groups with regard to the clinical parameters during the evaluation period. The mean bone loss in the first year of functioning was 0.6 mm in both groups. With regard to the gingiva score, plaque score, bleeding score or bone loss between T0 and T12, no associations were found with the presence of the cultured microorganisms. An association was present between pockets >or= 4 mm and the presence of Peptostreptococcus micros in the two-stage group. CONCLUSIONS: The short-term results indicate that two-part implants inserted in a one-stage procedure may be as predictable as inserted in the common two-stage procedure. The peri-implant sulcus can and does harbour potential periodontal pathogens without significant signs of tissue breakdown.     

The diphtheria toxin/urokinase fusion protein (DTAT) is selectively toxic to CD87 expressing leukemic cells

Diphtheria fusion proteins are a novel class of agents for the treatment of chemotherapy resistant acute myelogenous leukemia (AML). We prepared diphtheria toxin/urokinase fusion protein (DTAT) composed of the amino terminal fragment of the urokinase-type plasminogen activator (uPA) fused to the catalytic and translocation domains of diphtheria toxin (DT) and assessed its activity on leukemic cell lines. The number of uPA receptors (uPAR or CD87) was measured using a phycoerythrin conjugated monoclonal antibody to CD87 and flow cytometry. Seven of 23 cell lines (30%) showed CD87 expression (> or =5000 receptors/cell). DTAT cytotoxicity (IC(50)< or =30pM) was observed in all seven of these samples and none of the 16 samples with low or absent CD87 expression. There was a significant correlation between DTAT sensitivity and CD87 density (P=0.0007). These results show that specific CD87 binding is one factor important in the sensitivity of patient's leukemic blasts to DTAT and demonstrate for the first time that the CD87/uPAR can be used as a target for fusion protein therapy of AML.     

Performance improvement based on integrated quality management models: what evidence do we have? A systematic literature review.

PURPOSE: Health care organizations have to improve their performance for multiple stakeholders and organize integrated care. To facilitate this, various integrated quality management models can be used. This article reviews the literature on the Malcolm Baldrige Quality Award (MBQA) criteria, the European Foundation Quality Management (EFQM) Excellence model (Excellence award models) and the Chronic Care Model. The focus is on the empirical evidence for improved performance by the implementation of interventions based on these models. DATA SOURCES: A systematic literature review from 1995 to May 2006 in the Pubmed, Cochrane, and ABI- databases was conducted. STUDY SELECTION: After selection, 37 studies were included, 16 in the Excellence award model search and 21 in the Chronic Care Model search. DATA EXTRACTION AND RESULTS OF ANALYSIS: Data were retrieved about the main intervention elements, study design, evidence level, setting and context factors, data collection and analysis, principal results and performance dimensions. No Excellence Award model studies with controlled designs were found. For the Chronic Care Model, one systematic review, one meta analysis and six controlled studies were included. Seventeen studies (2 in Excellence award model, 15 in Chronic Care Model) reported one or more significant results. CONCLUSION: There is some evidence that implementing interventions based on the 'evidence-based developed' Chronic Care Model may improve process or outcome performances. The evidence for performance improvement by interventions based on the 'expert-based developed' MBQA criteria and the EFQM Excellence model is more limited. Only a few studies include balanced measures on multiple performance dimensions. Considering the need for integrated care and chronic care improvement, the further development of these models for guiding improvements in integrated care settings and their specific context factors is suggested.     

Pharmacological properties of parenteral cephalosporins: rationale for ambulatory use

Parenteral cephalosporins are among the most frequently used antibiotics in hospital therapy. They are characterised by an extended spectrum of activity against gram-positive and gram-negative bacteria, and some also have good activity against anaerobes. They kill proliferating bacterial cells rapidly, and generally show only a low tendency to select resistant mutants. However, there are cephalosporin compounds which induce cephalosporinases very rapidly in certain microorganisms. Together with other beta-lactam antibiotics, parenteral cephalosporins interfere with bacterial cell wall synthesis by inhibiting peptidoglycan cross-linkage. Because of this specific target, they are nontoxic to mammalian cells, and have a very favourable adverse effect profile. The chemical stability of parenteral cephalosporins in aqueous solution is good. After intravenous injection, high concentrations of these agents are achieved in serum and tissue. Most cephalosporins are eliminated unchanged via the kidney, with a half-life of 1 to 2 hours. But there are also derivatives with a serum half-life of more than 2 and up to 8 hours, allowing 12- or 24-hour dosage intervals. Because of their reliable efficacy and low risk of adverse effects, the parenteral cephalosporins offer a high degree of tolerability even in the setting of outpatient antibiotic therapy. In particular, the derivatives of the third generation are characterised by unique pharmacological properties.     

From the reason for consultation to the result of consultation in (pediatric) surgery

For the first time in the literature we have tried to open up the region of applied surgery to research. We noticed that there are many unsolved problems awaiting clarification. The aim of our study was to find out how often we could come to an exact diagnosis by our consultation. With the help of imaging diagnostic facilities, the chemical pathology laboratory, and histological examination in connection with operation we were usually able to come to an exact diagnosis. However, patients with unclear abdominal pain where it is essential--amongst other diagnoses--to exclude acute appendicitis (as the most common condition with a potentially dangerous, but avoidable outcome) still present a lot of diagnostic problems. There are for example, no appropriate concepts as basis for the nomenclature of such unresolved cases.