[Meningitis (II)--acute bacterial meningitis]

Acute meningitis is a medical emergency, particularly in patients with rapidly progressing disease, mental status changes or neurological deficits. The majority of cases of bacterial meningitis are caused by a limited number of species, i.e. Streptococcus pneumoniae, Neisseria meningitis, Listeria monocytogenes, group B Streptococci (Streptococcus agalactiae), Haemophilus influenzae and Enterobacteriaceae. Many other pathogens can occasionally cause bacterial meningitis, often under special clinical circumstances. Treatment of meningitis includes two main goals: Eradication of the infecting organism, and management of CNS and systemic complications. Empiric therapy should be initiated without delay, as the prognosis of the disease depends on the time when therapy is started. One or two blood cultures should be obtained before administering the first antibiotic. Empiric therapy is primarily based on the age of the patient, with modifications if there are positive findings on CSF gram stain or if the patient presents with special risk factors. It is safer to choose regimens with broad coverage, as they can usually be modified within 24-48 hours, when antibiotic sensitivities of the infecting organism become available. Adjunctive therapy with dexamethasone is also administered in severely ill patients concomitantly with the first antibiotic dose. In patients who are clinically stable and are unlikely to be adversely affected if antibiotics are not administered immediately, including those with suspected viral or chronic meningitis, a lumbar puncture represents the first step, unless there is clinical suspicion of an intracerebral mass lesion. Findings in the CSF and on CT scan, if performed, will guide the further diagnostic work-up and therapy in all patients.

Orbital venous malformation: percutaneous treatment using an electrolytically detachable fibred coil

PURPOSE: To report the efficacy of percutaneous treatment of an orbital venous malformation with an electrolytically detachable fibred coil. METHODS: We report an instance of radiography-guided percutaneous treatment with an electrolytically detachable fibred coil in a 16-year-old boy with acute, spontaneous, painless proptosis on the left side, which progressed with time. RESULTS: Magnetic resonance imaging, angiography and orbitophlebography revealed a low-flow, intraorbital venous malformation. Percutaneous puncture and drainage were followed by a short remission. Following an acute recurrence, a single detachable fibred coil was deployed via a percutaneous approach under angiographic guidance. No radiological or clinical recurrences were observed over 4 years. CONCLUSIONS: Embolization of a deep orbital venous malformation with detachable fibred coils via a percutaneous approach can be highly effective, and may be considered before proceeding with open surgery.

[Manifestation and course of coronary heart disease in men and women--consequences for diagnosis and treatment]

Gender related issues in manifestation, diagnosis and treatment of coronary artery disease are important but still not well recognized. Women are more likely to present late after first symptoms of myocardial infarction. Myocardial infarction is more often unrecognized. In regard to complications after myocardial infarctions ventricular tachycardia and cardiac arrest are more frequent and women are also more likely to develop heart failure or cardiogenic shock. The reason for this is most probably the fact that women presenting with myocardial infarction are of older age and have a higher incidence of co-morbidities. Thrombolysis and coronary angioplasty are less often performed in women in the setting of myocardial infarction. However there is a clear trend toward improvement of this situation during the last years. The reopening rate of occluded coronary arteries with thrombolysis and with coronary angioplasty is similar in women compared to men. Perioperative risk with aorto-coronary bypass surgery is higher in women, which can not be fully explained by higher age and co-morbidities. However 10 years survival rate after aorto-coronary bypass-surgery is similar for men and women, although occlusion of venous grafts is seen more often in women. The benefit of structured cardiac rehabilitation after an acute event is similar for younger and older women and as good as in men. Positive effects of cardiac rehabilitation include increased physical performance, reduction of body fat, improvement of lipid-profiles and an improvement of the psychosocial situation and quality of life.

Stent-grafts in the treatment of emergent or urgent carotid artery disease: review of 25 cases

PURPOSE: To report the authors' initial experience with carotid artery stent-grafts in a comparatively large patient series for the treatment of acute bleeding and impending rupture or the prevention of distal embolization. MATERIALS AND METHODS: This retrospective study was approved by the institutional review boards and performed according to HIPPA standards. Twenty-five patients were treated with 27 carotid artery stent-grafts (Gore Viabahn, n = 10; Bard Fluency, n = 9; polytetrafluoroethylene-covered Palmaz, n = 5; and Wallgraft, n = 3). Thirteen stent-grafts were placed in patients with carotid blow-out syndrome (including three patients with carotid-airway fistula), 12 in patients with either pseudoaneurysm (n = 9) or true aneurysm (n = 3), and two in patients with intractable high-grade bare stent restenosis. RESULTS: The technical success rate was 100% (27 of 27 cases). No acute procedural transient ischemic attacks or strokes occurred. Procedural dissections occurred in two of the 27 cases (7.4%). Short-term complications occurred in three of the 27 cases (11%) (repeat hemorrhage, n = 2; common carotid artery occlusion, n = 1). The overall patient mortality rate was 36% (nine of 25 patients, all with carotid blow-out syndrome). Six-month follow-up in 15 of the 16 living patients demonstrated widely patent stent-grafts. Two patients with pseudoaneurysm also demonstrated patent stents at 18- and 33-month follow-up. CONCLUSIONS: Stent-grafts may be useful in the treatment of carotid artery bleeding syndrome, aneurysm, and stenosis, with a high procedural success rate in selected cases. The results of mid-term follow-up are encouraging, but results of long-term follow-up must be evaluated in future studies.

[Acute headache in a case of cerebral cavernomas]

We report a case of a 52-year-old female patient with known cerebral cavernomas and acute headache. A cranial CT scan excluded an intracranial bleeding. Cavernomas are rare vascular malformations of the venous blood system (synon. cavernous angiomas) with a slow blood flow. Clinical manifestation is presented between an age of 30-50 years with mostly unspecific neurological symptoms like headache, nausea, vomiting and dizziness, but also epileptic seizures and bleedings may occur. In general, therapy is symptomatic. In cases of seizures, however, anticonvulsive treatment is indicated. Operation can be discussed for peripheral localized cavernomas with bleeding or for refractory seizures. If antiplatelet or anticoagulation therapy is necessary due to other diseases (coronary heart disease, atrial fibrillation, thrombosis, pulmonary embolism), cerebral cavernomas are not considered as an absolute contraindication. The risk for an ischemic stroke under atrial fibrillation (5-20%), for example, is higher than the risk for bleeding of a cerebral cavernoma under anticoagulation therapy.

Good manufacturing practice-compliant validation and preparation of BM cells for the therapy of acute myocardial infarction

BACKGROUND: Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was established by the Cytonet group. METHODS: As well as fulfillment of standard GMP requirements, including a manufacturing license, validation of the preparation process and the final product was performed. Whole blood (n=6) and BM (n=3) validation samples were processed under GMP conditions by gelafundin or hydroxyethylstarch sedimentation in order to reduce erythrocytes/platelets and volume and to achieve specifications defined in advance. Special attention was paid to the free potassium (<6 mmol/L), some rheologically relevant cellular characteristics (hematocrit <0.45, platelets <450 x 10(6)/mL) and the sterility of the final product. RESULTS: The data were reviewed and GMP compliance was confirmed by the German authorities (Paul-Ehrlich Institute). Forty-five BM cell preparations for clinical use were carried out following the validated methodology and standards. Additionally three selections of CD34+ BM cells for infusion were performed. All specification limits were met. Discussion In conclusion, preparation of BM cells for intracoronary application is feasible under GMP conditions. As the results of sterility testing may not be available at the time of intracoronary application, the highest possible standards to avoid bacterial and other contaminations have to be applied. The increased expense of the GMP-compliant process can be justified by higher safety for patients and better control of the final product.

[Nursing unit: nurses co-ordinating hospital care--an answer to new challenges in acute medicine]

Some patients at university hospital no longer need frequent medical treatment but complex professional nursing care. At University Hospital (Inselspital) Bern a Nursing Unit with six beds was run as a pilot project based on experiences in British Nursing Development Units. The care concept was specifically developed and based on a definition of professional nursing, an evidence-based practice approach, resource oriented self management, and caring. Primary nursing was used, and the primary nurse was responsible for the coordination and steering of patient care. The project was evaluated prospectively. During the pilot phase, 37 patients were cared for on the NU. On average, 85% of the beds were occupied, patients were hospitalized for 21.5 days and had a mean age of 68.9 years. They were older than the University Hospital's average patient, and cases were more complex than the University Hospital's average case. The nurses' experiences were mainly positive. Their enhanced responsibility and the structured care process were seen as a challenge allowing them to enlarge their abilities. With this project, the University Hospital built up innovative services for patients with complex nursing problems. The project showed that well trained nurses can take on more responsibility for this patient group than in the context of conventional care models.

Acute Stroke: Present and Future of Catheter-Based Interventions

Acute ischemic stroke is a major cause of morbidity and mortality in industrialized nations. The sequel of stroke ranges from mild to severe disability and even death. Since the impairment may be permanent, the costs to society from work incapacity and the need for long-term care can be high. Additionally, the burden of suffering associated with the disease may have devastating effects on individuals and families.Following the occlusion of a cerebral vessel, the full extent of the infarction may not become clinically and radiologically apparent until days after. By then, the surrounding watershed zone, or penumbra, either survives or succumbs to necrosis over time. The natural history of this "tissue at risk" is determined by two factors: the collateralization from other vascular territories and the possible occurrence of spontaneous recanalization of the occluded vessel. The current treatment options for acute ischemic stroke are aiming at an early and sustained restoration of flow to the penumbra. The effect of the treatment is therefore time-dependent and the neurologic outcome is a function of the time span between onset of symptoms and recanalization therapy as well as of the recanalization rate associated with a specific treatment.This report summarizes the results of the major trials on catheter-based interventions, either using thrombolytic drugs or novel mechanical approaches being developed to treat patients with acute ischemic stroke.

Heparin-induced thrombocytopenia: some working hypotheses on pathogenesis, diagnostic strategies and treatment

PURPOSE OF REVIEW: The present contribution will illustrate some evolving concepts on the pathogenesis and clinical management of heparin-induced thrombocytopenia (HIT) and describe how we approach patients with suspected HIT at our institution. RECENT FINDINGS: HIT is caused by an autoimmune reaction leading to the formation of antibodies directed against platelet factor 4. Conditions favoring the development of anti-platelet factor 4/heparin antibodies differ from those required for the formation of macromolecular ternary complexes (HIT antibody/platelet factor 4/heparin), which are able to activate platelets and induce clinical HIT. HIT can be diagnosed by combining its pretest probability with the quantitative result of rapid HIT-antibody assays. Treatment of acute HIT requires inhibition of in-vivo thrombin generation by means of alternative nonheparin anticoagulant drugs, whose effective dosage appears to be significantly lower than the official recommendations. As HIT antibodies are transient, HIT patients can be re-exposed to heparin, provided that previous heparin treatment is remote and that anti-platelet factor 4/heparin antibodies are undetectable. SUMMARY: In recent years, there has been a continuing elucidation of pathogenic and clinically relevant issues, which are intellectually rewarding to follow and should enable us to offer a steadily improving treatment to the HIT patients we are in charge of.

Multi-vessel stenting during primary percutaneous coronary intervention for acute myocardial infarction. A single-center experience

BACKGROUND: Recanalization of the culprit lesion is the main goal of primary angioplasty for acute ST-segment elevation myocardial infarction (STEMI). Patients presenting with acute myocardial infarction and multivessel disease are, therefore, usually subjected to staged procedures, with the primary percutaneous coronary intervention (PCI) confined to recanalization of the infarct-related artery (IRA). Theoretically at least, early relief of stenoses of non-infarct-related arteries could promote collateral circulation, which could help to limit the infarct size. However, the safety and feasibility of such an approach has not been adequately established. METHODS: In this single-center prospective study we examined 73 consecutive patients who had an acute STEMI and at least one or more lesions > or = 70% in a major epicardial vessel other than the infarct-related artery. In the first 28 patients, forming the multi-vessel (MV) PCI group, all lesions were treated during the primary procedure. In the following 45 patients, forming the culprit-only (CO) PCI group, only the culprit lesion was treated during the initial procedure, followed by either planned-staged or ischemia-driven revascularization of the non-culprit lesions. Fluoroscopy time and contrast dye amount were compared between both groups, and patients were followed up for one year for major adverse cardiac events (MACE) and other significant clinical events. RESULTS: The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the MV-PCI group, 2.51 lesions per patient were treated using 2.96 +/- 1.34 stents (1.00 lesions and 1.76 +/- 1.17 stents in the CO-PCI group, both p < 0.001). The fluoroscopy time increased from 10.3 (7.2-16.9) min in the CO-PCI group to 12.5 (8.5-19.3) min in the MV-PCI group (p = 0.22), and the amount of contrast used from 200 (180-250) ml to 250 (200-300) ml, respectively (p = 0.16). Peak CK and CK-MB were significantly lower in patients of the MV-PCI group (843 +/- 845 and 135 +/- 125 vs 1652 +/- 1550 and 207 +/- 155 U/l, p < 0.001 and 0.01, respectively). Similar rates of major adverse cardiac events at one year were observed in the two groups (24% and 28% in multi-vessel and culprit treatment groups, p = 0.73). The incidence of new revascularization in both infarct- and non-infarct-related arteries was also similar (24% and 28%, respectively, p = 0.73). CONCLUSION: We may state from this limited experience that a multi-vessel stenting approach for patients with acute STEMI and multi-vessel disease is feasible and probably safe during routine clinical practice. Our data suggest that this approach may help to limit the infarct size. However, larger studies, perhaps using drug-eluting stents, are still needed to further evaluate the safety and efficiency of this procedure, and whether it is associated with a lower need of subsequent revascularization and lower costs.

Acute coronary syndromes: management and secondary prevention

Acute coronary syndromes represent a broad spectrum of ischemic myocardial events including unstable angina, non-ST elevation myocardial infarction and acute ST elevation myocardial infarction, which are associated with high morbidity and mortality. They constitute the most frequent cause of hospital admission related to cardiac disease. Early diagnosis and risk stratification are essential for initiation of optimal medical and invasive management. Therapeutic measures comprise aggressive antiplatelet, antithrombotic, and anti-ischemic agents. In addition, patients with high-risk features, notably positive troponin, ST segment changes and diabetes, benefit from an early invasive as compared to a conservative strategy. Importantly, lifestyle interventions, modification of the risk factor profile, and long-term medical treatment are of pivotal importance in reducing the long-term risk of recurrence.

Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia

Disseminated adenoviral infection with hepatitis is rare in children undergoing standard chemotherapy. We report on a 3(1/2)-year-old male with fatal adenovirus hepatitis receiving maintenance chemotherapy for acute lymphoblastic leukemia (ALL). Adenoviral hepatitis was proven by histology, viral culture, and PCR in a liver biopsy. Quantitative real-time PCR in the peripheral blood showed adenoviral DNA copy number >10(9)/ml. Despite aggressive supportive care and antiviral treatment with cidofovir, the patient died rapidly due to fulminant liver failure. Diagnostic and treatment options for adenovirus infection remain unsatisfactory for these patients. We propose suggestions for diagnosis and therapy.

Obesity in long-term survivors of childhood acute lymphoblastic leukemia

BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates reaching 80% emphasizes the necessity to determine treatment related long-term effects. The present study examines the prevalence of and the risk factors for overweight and obesity in a cohort of ALL survivors treated and living in the French speaking part of Switzerland. METHODS: In this retrospective two-center study, height and weight of 54 patients diagnosed with ALL in first complete remission and treated with chemotherapy only were recorded at specified time points during treatment and off-therapy. Body mass index (BMI) and its age- and gender-adjusted standard deviation score (BMI-SDS) were calculated for the patients and their parents separately. Overweight and obesity were defined by a threshold of BMI-SDS >1.645 and BMI-SDS >1.96, respectively. RESULTS: At last follow-up, 16 (30%) of the 54 survivors were overweight and 10 (18%) were obese. The off-treatment period was most at risk with 11 of the 16 becoming overweight and 9 of the 10 becoming obese during that period. Overweight/obesity at diagnosis and abnormal maternal BMI were significantly associated with abnormal weight at follow-up, while age at diagnosis, gender, cumulative dose of steroids and paternal BMI showed no association. CONCLUSIONS: Consistent with published evidence from other regions of the developed and developing world, there is a significant prevalence of obesity in young ALL survivors in the French speaking part of Switzerland. Factors significantly associated with this late effect were mostly related to the familial background rather than to the treatment components.

Non-classical karyotypic features in relapsed childhood B-cell precursor acute lymphoblastic leukemia

Karyotype analysis of acute lymphoblastic leukemia (ALL) at diagnosis has provided valuable prognostic markers for treatment stratification. However, reports of cytogenetic studies of relapsed ALL samples are limited. We compared the karyotypes from 436 nonselected B-cell precursor ALL patients at initial diagnosis and of 76 patients at first relapse. We noticed a relative increase of karyotypes that did not fall into the classic ALL cytogenetic subgroups (high hyperdiploidy, t(12;21), t(9;22), 11q23, t(1;19), <45 chromosomes) in a group of 29 patients at relapse (38%) compared to 130 patients at presentation (30%). Non-classical cytogenetic aberrations in these 29 patients were mostly found on chromosomes 1, 2, 7, 9, 13, 14, and 17. We also describe six rare reciprocal translocations, three of which involved 14q32. The most frequent abnormalities were found in 9p (12/29 cases) and were associated with a marked decrease in the duration of the second remission, but not of the probability of 10-year event-free survival after relapse treatment. From 29 patients with non-classical cytogenetic aberrations, only 8 (28%) had been stratified to a high risk-arm on the first treatment protocol, suggesting that this subgroup might benefit from the identification of new prognostic markers in future studies.

Overview of the pathology of three widely used animal models of acute lung injury

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are syndromes of acute diffuse damage to the pulmonary parenchyma by a variety of local or systemic insults. Increased alveolar capillary membrane permeability was recognized as the common end organ injury and a central feature in all forms of ALI/ARDS. Although great strides have been made in understanding the pathogenesis of ALI/ARDS and in intensive care medicine, the treatment approach to ARDS is still relying on ventilatory and cardiovascular support based on the recognition of the clinical picture. In the course of evaluating novel treatment approaches to ARDS, 3 models of ALI induced in different species, i.e. the surfactant washout lavage model, the oleic acid intravenous injection model and the endotoxin injection model, were widely used. This review gives an overview of the pathological characteristics of these models from studies in pigs, dogs or sheep. We believe that a good morphological description of these models, both spatially and temporally, will help us gain a better understanding of the real pathophysiological picture and apply these models more accurately and liberally in evaluating novel treatment approaches to ARDS.