[Risks of progression of cerebrovascular pathology associated with the activity of the brain purinergic system]. / Riski progressirovaniya tserebrovaskulyarnoi patologii, svyazannye s aktivnost'yu purinergicheskoi sistemy mozga.

Until now, there is no understanding of the relationship between risk factors and the progression of cerebrovascular pathology. The review presents facts that confirm the involvement of various subtypes of purine P2 receptors in neuron activation, growth and myelination of axons, migration and microglia phagocytosis, astrogliosis, regulation of vascular tone, thrombosis and angiogenesis, neuroinflammation and immune responses. The data suggest the possibility of the activation of purinergic system of the brain during the development of main risk factors for cerebrovascular pathology (age, arterial hypertension, diabetes), as a stereotypical mechanism that can affect the homeostasis of the ensemble "neuron-glia-capillary". Purinergic P2 receptors may be a potential target for the development of pharmacological methods to limit the progression of cerebrovascular pathology.

Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer.

BACKGROUND: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. METHODS: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. RESULTS: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). CONCLUSION: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

Activated macrophages containing tumor marker in colon carcinoma: immunohistochemical proof of a concept.

The presence of carcinoembryonic antigen (CEA)-containing activated macrophages has been demonstrated in peripheral blood from patients with colorectal carcinoma. Macrophages migrate from the circulation into the tissue, phagocytose debris, and return to the bloodstream. Hence it seems likely that activated macrophages containing tumor debris, i.e., tumor marker, are present in the stroma of colorectal carcinoma. After phagocytosis, they could follow a hematogenic or lymphogenic route to the peripheral blood. The aim of this study is to assess the presence of tumor marker-containing activated macrophages in the stroma of colon carcinoma and in regional lymph nodes. From 10 cases of colon carcinoma, samples of tumor tissue and metastasis-free lymph nodes were cut in serial sections and stained for CD68 to identify macrophages and for CEA, cytokeratin, or M30 presence. Slides were digitalised and visually inspected using two monitors, comparing the CD68 stain to the tumor marker stain to evaluate the presence of tumor marker-positive macrophages. Macrophages containing tumor marker could be identified in tumor stroma and in metastasis-free regional lymph nodes. The distribution varied for the different markers, CEA-positive macrophages being most abundant. The presence of macrophages containing tumor marker in the tumor stroma and lymph nodes from patients with colon carcinoma could be confirmed in this series using serial immunohistochemistry. This finding supports the concept of activated macrophages, after phagocytosing cell debris, being transported or migrating through the lymphatic system. These results support the potential of tumor marker-containing macrophages to serve as a marker for diagnosis and follow-up of colon cancer patients.

[Acute intoxication with isopropanol]. / Akute Intoxikation mit Isopropanol.

Isopropanol is an ingredient of commonly used industrial and household agents. Intoxication can occur unintentionally, in suicide attempts or by alcohol abusers when used as a substitute for ethanol. Symptoms involve the gastrointestinal tract, the central nervous system, and the cardiovascular system at higher doses. Mortality is especially high in patients with deep coma and marked hypotension. This report describes a case of life-threatening isopropanol intoxication of a prison inmate successfully treated by haemodialysis.

[Subcutaneous nodules with malignant presentation, but caused by infection]. / Een subcutane zwelling met een maligne presentatie, maar met een infectieuze oorzaak.

Three patients, a woman aged 32, a boy aged 6.5 and a man aged 56 years, presented with a subcutaneous mass suggesting a malignancy: respectively a rubbery swelling, painful to the touch below the left scapula, a partly massive, partly soft swelling on the inside of the left upper leg, and a non-fluctuating mass near the right eighth rib, parasternally. Additional diagnostic investigation revealed an infectious cause: respectively Mycobacterium tuberculosis, Bartonella henselae and Salmonella typhi. Antimicrobial therapy was successful. Subcutaneous masses suspected of being a benign or malignant tumour are sometimes caused by an infection. The differential diagnosis is extensive. Sometimes the travel anamnesis yields helpful information. It is concluded that besides histopathological examination, microbiological investigation can play a major role in the evaluation of subcutaneous masses.

Fourier analysis reveals increased trabecular spacing in sickle cell anemia.

Sickle cell anemia may expand marrow spaces in the jaws. Fourier analysis is well-suited to the analysis of trabecular spacing in radiographs. We hypothesize that individuals with sickle cell anemia demonstrate increased intertrabecular spacing. Periapical radiographs of 18 African Americans with sickle cell disease and 18 controls were examined by one-dimensional discrete Fourier analyses in both jaws for measurement of the spatial frequency distribution of repeating trabecular structures. A strut analysis of trabeculae was also performed and the results compared. Trabecular structures in individuals with sickle cell anemia revealed increased intertrabecular distance compared with controls. Strut analysis revealed significant reductions in trabecular complexity. Fourier analysis allows for the classification of subjects with 94% sensitivity and specificity. Fourier analysis of dental radiographs is a more effective method of identifying individuals with sickle cell anemia than strut analysis.

[Antiarrhythmic therapy in patients with heart failure]. / Therapie kardialer Arrhythmien bei Herzinsuffizienz.

In patients with severe chronic heart failure, many deaths are sudden due to life-threatening ventricular arrhythmias. Supraventricular arrhythmias such as paroxysmal or chronic atrial fibrillation may also cause serious complications in those patients due to acute loss of atrial contraction, pump failure during rapid ventricular response and embolic events. Two therapeutic strategies are currently available for therapy and prevention of malignant ventricular arrhythmias and subsequent sudden arrhythmic death: antiarrhythmic drug therapy and implantable defibrillators. However, selection of the most beneficial strategy for the individual patient to reduce the risk of sudden death remains a major challenge in cardiology. Betablockers exert a favorable antiarrhythmic action without increasing proarrhythmia, thus betablockers may serve as a basic medication in patients at risk for sudden death. However, the general use of antiarrhythmic drug therapy for symptomatic ventricular arrhythmias is not recommended, as these drugs have been shown to increase mortality in patients with severe congestive heart failure due to proarrhythmic or negative inotropic effects (e.g. class Ia antiarrhythmics). Even class III antiarrhythmic drugs such as amiodarone, which has been studied sufficiently in patients with left ventricular dysfunction, is not effective enough for significant reduction of cardiac mortality in patients with symptomatic ventricular arrhythmias and depressed ventricular function (e.g. EMIAT, CAMIAT). But as a positive result of available studies, amiodarone does not increase mortality in those patients. Dofetilide has also not been shown to prolong life significantly by suppressing malignant ventricular arrhythmias (DIAMOND-Study). In patients with symptomatic ventricular arrhythmias or aborted sudden death, ICD therapy has been proven to be superior to antiarrhythmic drug therapy in cardiac mortality reduction as a secondary prevention strategy (e.g. AVID, CASH, CIDS). For primary prevention of sudden arrhythmic death in high risk patients, 2 studies (MADIT, MUSST) have already demonstrated favorable results, decreasing mortality by ICD therapy in selected patient populations with partly-reduced ventricular function and unsustained but inducible ventricular tachycardias. This topic is, however, undergoing further evaluation by ongoing trials (e.g. MADIT II, SCD-HeFT). From available data, antiarrhythmic drug therapy in high risk patients is not justified on a routine basis, whereas ICD therapy as a secondary and perhaps primary prevention strategy will significantly reduce cardiac mortality in patients with severe heart failure. Sotalol, a class III antiarrhythmic agent, has recently been shown to reduce ICD-shock delivery which indicates that concomitant drug therapy in patients with an ICD device already implanted may be beneficial in terms of reducing ICD discharges due to ventricular and supraventricular tachycardias. In patients with paroxysmal atrial fibrillation and congestive heart failure, restitution of sinus rhythm is the primary therapeutic goal which can be safely achieved by amiodarone and dofetilide (DIAMOND). In the latter, continuous monitoring of the patient is mandatory because of increased risk of torsade de pointes arrhythmias during the first days of drug administration. In patients with chronic atrial fibrillation rate control and anticoagulation with warfarin is the primary therapeutic option, which can be achieved with either drug treatment (Digoxin, betablockers, amiodarone) or by His bundle ablation with subsequent pacemaker insertion.

Adenosine in treating cardiac arrhythmias.

1. Adenosine is an endogenous nucleoside which causes a brief blockade of the AV nodal conduction pathway following intravenous administration. 2. Such a brief AV block can be used therapeutically for reliable termination of AV nodal re-entry tachycardia and WPW re-entry tachycardia. It can also be used for demasking atrial activity in rapid suspected supraventricular tachycardia with a broad QRS complex or a Delta wave, not present during sinus rhythm with normal AV node conduction, indicating the presence of a hidden WPW syndrome. 3. Side effects after adenosine application are frequent, but very transient rarely serious (1-3% of cases, e.g. status asthmaticus, ventricular fibrillation) and therefore require a certain degree of experience with this drug on the part of the treating physician.

Torsade de pointes complicating drug treatment of low-malignant forms of arrhythmia: four cases reports.

In patients with malignant ventricular arrhythmias, antiarrhythmic therapy is known to carry a substantial risk of proarrhythmia. This risk is usually considered to be low when supraventricular arrhythmias or benign ventricular arrhythmias are considered. We were able to collect data on four patients without a history of life-threatening arrhythmias, in whom antiarrhythmic therapy was used and resulted in documented ventricular fibrillation or torsade de pointes. In Cases No. 1 and 2, atrial fibrillation was treated with either quinidine or quinidine and sotalol in combination. In both patients Holter monitoring, 4-12 h after conversion to sinus rhythm, documented the spontaneous occurrence of torsade de pointes degenerating into ventricular fibrillation and requiring DC shock for termination. In Case No. 3, atrial fibrillation was treated with sotalol and amiodarone for 2 months when incessant episodes of torsade de pointes were documented. In Case No. 4, frequent but unsustained ventricular arrhythmias were treated with amiodarone in a patient suffering dilative cardiomyopathy. After 6 days of treatment at a heart rate of 54 beats/min, a marked QT increase was associated with the occurrence of repetitive episodes of polymorphic ventricular tachycardia degenerating into ventricular fibrillation. None of the patients presented significant electrolyte abnormalities in the laboratory. A pathologic increase of the QTc-time was documented in Cases No. 1, 3, and 4. In all patients antiarrhythmic therapy was withdrawn after the proarrhythmic event and the patient became free of malignant tachyarrhythmias. Antiarrhythmic therapy also carries a considerable risk of proarrhythmia when "benign" cardiac arrhythmias are treated. The risk seems to be lower than in patients with malignant arrhythmias, however it includes the occurrence of lethal tachyarrhythmias. Special attention should be paid to the selection of antiarrhythmic agents when used in combination.

Radioimmunoassay of beta-endorphin in ventricular and lumbar cerebrospinal fluid.

We describe a sensitive beta-endorphin (beta-EP) radioimmunoassay specific for beta-EP 1-31 applied to human ventricular and lumbar cerebrospinal fluid (CSF). Specificity was documented by reversed-phase HPLC of CSF pools. Simultaneous ventricular and lumbar CSF samples from 13 patients suspected of having normal-pressure hydrocephalus showed median beta-EP values of 2.2 (range 1.7-4.0) and 4.8 (2.8-14.6) pmol/L, respectively. Ventricular and lumbar beta-EP concentrations were positively correlated (Spearman r = 0.72, P = 0.013). The beta-EP rostral-caudal gradient was closely related to the CSF protein gradient. HPLC profiles of beta-EP immunoreactivity were similar in ventricular and lumbar CSF with both C- and N-terminal antisera. beta-EP concentrations did not vary in the first 12 mL of lumbar CSF, tapped in 3-mL portions [F(3,32) = 0.42, P = 0.74]. The beta-EP concentration in lumbar CSF from 15 children in remission from acute leukemia [23.4 (15.0-27.1) pmol/L] was higher than in 54 healthy adults [11.7 (10.9-13.3) pmol/L; P less than 0.01]. There was no effect of sex or age on CSF beta-EP in adults. beta-EP in lumbar human CSF may indicate di- and mesencephalic beta-EP neuronal activity.

Short-term and long-term problems after duraplastic enlargement of anterior abdominal wall.

Between 1974 and 1989, 49 out of 83 children with gastroschisis or omphalocele underwent duraplastic enlargement of the anterior abdominal wall. The solvent dried dura proved to be the most useful material, which could be left in place even after a scar had formed. Abdominal complications depend on preexisting damage of the intestine and on the intraabdominal pressure resulting from closure. Long-term disturbances of the gastrointestinal and abdominal wall function are comparable to the results of other reconstructive methods.