A diagnostic flowchart, including TCD, Xe-CT and angiography, to improve the diagnosis of vasospasm critically affecting cerebral blood flow in patients with subarachnoid haemorrhage, sedated and ventilated.

The aim of this study was to prospectively evaluate a clinical protocol including transcranial doppler (TCD), Xenon-CT (Xe-CT) and angiography, for the detection of vasospasm leading to critical reductions of regional cerebral blood flow (rCBF) in both ventilated and sedated SAH patients, i.e. patients in whom clinical evaluation was not possible. Seventy-six patients were prospectively included in a surveillance protocol for daily TCD vasospasm monitoring. When TCD showed a V(mean) above 120 cm/sec in the middle cerebral artery (MCA), patients underwent Xe-CT study. If rCBF in the MCA was reduced to below 20 ml/100 g/min or if there was a reduction in the rCBF with significant asymmetry between the two MCAs, angiography was performed. Conversely, further Xe-CT and angiography were not obtained unless the TCD V(mean) values reached values above 160 cm/sec. In 35 patients, V(mean) attained values above 120 cm/sec, but only in five of them, rCBF was suggestive of vasospasm, and angiography confirmed the diagnosis in four. The protocol suggests that in sedated and ventilated patients, detection of a critical rCBF reduction due to vasospasm is possible to allow for more specific treatment and to reduce undue medical complications.

Aging of bone marrow mesenchymal stromal/stem cells: Implications on autologous regenerative medicine.

With their proliferation, differentiation into specific cell types, and secretion properties, mesenchymal stromal/stem cells (MSC) are very interesting tools to be used in regenerative medicine. Bone marrow (BM) was the first MSC source characterized. In the frame of autologous MSC therapy, it is important to detect donor's parameters affecting MSC potency. Age of the donors appears as one parameter that could greatly affect MSC properties. Moreover, in vitro cell expansion is needed to obtain the number of cells necessary for clinical developments. It will lead to in vitro cell aging that could modify cell properties. This review recapitulates several studies evaluating the effect of in vitro and in vivo MSC aging on cell properties.

Diagnostic impact of the spectrum of ischemic cerebral blood flow thresholds in sedated subarachnoid hemorrhage patients.

OBJECTIVE: Ischemia is the main cause of secondary damage in subarachnoid hemorrhage (SAH). Cerebral blood flow (CBF) measurement is useful to detect critical values. We analyzed the diagnostic impact of CBF ischemic thresholds to predict a new low attenuation area on computed tomography (CT) due to failure of large vessel perfusion. METHODS: We analyzed 48 xenon CT (Xe-CT) studies from 10 patients with SAH. CBF measurements were obtained by means of Xe-CT and cortical regions of interest (ROls). The ROIs which appeared in a hypoattenuation area were recorded. Cortical CBF was tested for specificity and sensitivity as a predictor of hypoattenuation by means of a receiver operating characteristic curve. RESULTS: Mean age was 58 (SD +/- 12.4) years. The median Fisher score and Hunt and Hess scale were 2 and 3, respectively. The area under the receiver operating characteristic curve was 0.912 (CI 0.896 to 0.926). The cut-off value for best accuracy was 6 mL/ 100 g/min, with a likelihood ratio of 37. CONCLUSION: The present study suggests a threshold of 6 mL/100 g/ min as a predictor of a new low attenuation area. However, each clinician should choose the most useful threshold according to pre-test probability and the cost/effectiveness ratio of the applied therapies.

Reperfusion of low attenuation areas complicating subarachnoid hemorrhage.

Hypoattenuation areas shown on brain CT scans after subarachnoid hemorrhage (SAH) are believed to be associated with persistent ischemia. The aim of this study was to evaluate regional cerebral blood flow (rCBF) in hypoattenuation areas and its evolution over time by means of Xenon CT (Xe-CT). We enrolled 16 patients with SAH who developed a hypoattenuation area in the middle cerebral artery territory. Patients were studied at time zero (the first Xe-CT), within 24 to 96 hours, and 96 hours after the initial Xe-CT. We analyzed 19 hypoattenuation areas caused by vascular distortion, vasospasm, or post-surgical embolization in 48 Xe-CT studies. Areas of hypoattenuation were divided in 2 groups according to initial rCBF. In the first group (n = 15), rCBF was initially above 6 mL/100 gr/min but only 2 were still ischemic (rCBF < 18 mL/ 100 gr/min) 96 hours after the first Xe-CT, while 7 (58%) were hyperemic. Conversely, in the second group with severe ischemia (rCBF < 6 mL/100 gr/min; n = 4) mean rCBF increased (p = 0.08) but still remained below the ischemic threshold. In severely ischemic lesions, rCBF reperfusion occurs but is probably marginally relevant. Conversely, in lesions not initially severely ischemic, residual CBF gradually improved and frequently became hyperemic. The functional recovery of these zones remains to be evaluated.

Estimated cerebral respiratory quotient and arteriovenous differences of CO2 in the ultra early detection of global ischemia in severe head injury.

The specificity of jugular bulb saturation (SjO2) and arteriovenous oxygen difference (AVDO2) to detect global cerebral ischemia remains controversial. An absolute increase in the arteriovenous difference of carbon dioxide tension (AVDpCO2) and, more specifically, the estimated respiratory quotient (eRQ = AVDpCO2/AVDO2) may indicate anaerobic CO2 production. We compared these variables with SjO2 to predict global cerebral ischemia. We selected 36 patients from a cohort of 69 consecutive patients suffering from severe traumatic brain injury. All patients had jugular bulb sampling within 6 hours after injury. Brain death at 48 hours was used as a surrogate index of irreversible ischemia to build a receiver operating characteristics (ROC) curve analysis. The mean (+/- standard deviation) eRQ in the 13 patients who died early (3.7 +/- 3.2 mmHg/ml/dl) was higher than the survivors (1.78 +/- 0.45 mmHg/ml/dl, P = 0.03). There was no differences in SjO2 between groups. The area under the ROC curves for eRQ, but not that of AVDpCO2, was greater (P = 0.04) than that of SjO2. The eRQ, more than AVDpCO2, appears to be a potentially more informative index of global cerebral ischemia than SjO2.

Cerebral blood flow in mean cerebral artery low density areas is not always ischemic in patients with aneurysmal subarachnoid hemorrhage--relationship with neurological outcome.

Aneurysmal subarachnoid hemorrhage (SAH) can be complicated by reduction of regional cerebral blood flow (rCBF) from large conductance vessels leading to focal edema appearing as an area of hypoattenuation on CT. In this study we included 29 patients with SAH due to aneurysmal rupture, having 36 CT low density areas within the middle cerebral artery territory in whom a total of 56 Xenon-CT (Xe-CT) studies were performed. Collectively, we evaluated 70 hypoattenuated areas. rCBF levels were measured in two different regions of interest drawn manually on the CT scan, one in the low density area and the other in a corresponding contralateral area of normal-appearing brain tissue. In the low density area (22.6 +/- 22.7 ml/100 gr/min) rCBF levels were significantly lower than in the contralateral area (32.8 +/- 17.1 7 ml/100 gr/min) (p = 0.0007). In the injured areas deep ischemia (CBF < 6 ml/ 100 g/min) was present in only 25.7% of Xe-CT studies, suggesting that hypodense areas are not always ischemic, whereas in 43.7% of the lesions/Xe-CT studies we found hyperemic values. Patients with a better outcome had hyperemic lesions, suggesting brain tissue recovery in injured areas.

Cerebral blood flow mapping in two different subtypes of intraparenchymal hemorrhagic traumatic lesions.

The pathogenesis and the viability of edematous tissue may be different in traumatic hematomas and traumatic contusions. We tested the hypothesis that mapping of regional Cerebral Blood Flow (rCBF) was different in these two subtypes of traumatic intraparenchymal lesions. We evaluated rCBF by means of Xenon-enhanced computerized tomography (Xe-CT) in 59 traumatic intracerebral lesions from 43 patients with severe head injury. One-hundred-nine intracerebral lesions/Xe-CT CBF measurements were obtained. The rCBF was measured in the hemorrhagic core, in the intralesional oedematous low density area and in a 1 cm rim of apparently normal perilesional parenchyma of both lesion subtypes. Not statistically significant lower rCBF levels were found in the edematous area of traumatic contusions. In traumatic hematomas rCBF levels were lower in the core than in the low density area, suggesting that rCBF in edematous area is marginally involved in the initial traumatic injury and that edema is probably influenced by the persistence of the hemorrhagic core. Conversely, in the traumatic contusions a difference in rCBF values was found between core, low density area and perilesional area, indicating that rCBF of the low density area is related to a concentrical distribution of the initial injury.

Clinical value of a peculiar nuclear fluorescence staining in systemic sclerosis.

Using unfixed rat liver sections as substrate for the detection of antinuclear antibodies, distinct nuclear staining was observed in the sera of patients with systemic sclerosis. Its reaction differed from previously described fluorescence patterns and was characterized by numerous fine speckles throughout the nucleus associated with one or more coarse lines. These lines were more evident in diluted sera, when fine speckled fluorescence faded. This picture "fine speckles with lines" (FLS) was defined. The FLS pattern was present in 35% of 91 patients with systemic sclerosis, while it was absent in 517 patients with rheumatic and non-rheumatic disorders and in 100 matched healthy subjects. Moreover, the FSL pattern was significantly associated with the diffuse subset of systemic sclerosis (50% of cases) and was related to the presence of anti-Scl-70 antibody. These results indicate that this fluorescent pattern of antinuclear antibodies may be considered a simple and very useful aid in the diagnosis and prognosis of systemic sclerosis.

Limitations of jugular bulb oxyhemoglobin saturation without intracranial pressure monitoring in subarachnoid hemorrhage.

We report a case of subarachnoid hemorrhage in which, even after having obtained a normal jugular bulb oxyhemoglobin saturation, cerebrovenous desaturation developed, and brain death occurred. The limitations of jugular bulb oxyhemoglobin saturation without intracranial pressure monitoring are discussed. We conclude that if increased intracranial pressure is suspected, use of jugular bulb oxyhemoglobin saturation monitoring alone would appear to be substantially limited.

Cerebral arteriovenous PCO2 difference and early global cerebral ischemia in a patient with acute severe head injury.

We report a case of acute head injury with severe diffuse brain swelling in which early global cerebral ischemia was followed by brain death. Global cerebral ischemia was detected by cerebral arteriovenous lactate content difference, cerebral arteriovenous carbon dioxide tension (PCO2) difference, and cerebral arteriovenous hydrogen ion content difference. Physiopathological aspects of cerebrovenous hypercarbia are discussed.

Cerebral arteriovenous oxygen difference and lactate-oxygen index: a case of bilateral monitoring.

We report a case of ruptured cerebral aneurysm that had uneven bilateral cerebral arteriovenous oxygen differences and lactate oxygen indexes. Guidelines are offered for determining which side to choose for jugular bulb catheterization. We conclude that bilateral catheterization may be useful in patients with severe hemispheric damage.

Prematurely detected traumatic carotid-cavernous sinus fistula, by means of unintentional contralateral inferior petrosal sinus catheterization: bilateral jugular bulb oxygen saturation findings.

A traumatic carotid-cavernous sinus fistula (CCSF) was prematurely suspected following the detection of arterial-like hemoglobin oxygen saturation values, sampled from a catheter placed for cerebrovenous monitoring. A high-resolution scan of jugular foramina revealed that the catheter tip had been unintentionally placed in the inferior petrosal sinus, contralateral to the CCSF, instead of in the superior jugular bulb. Jugular bulb hemoglobin oxygen saturation (SjO2), ipsilateral to CCSF, later approached arterial hemoglobin oxygen saturation (SaO2) values.The possibility and consequences of unintentional catheterization of the inferior petrosal sinus, and of extracerebral contamination of blood in the jugular bulb due to blood in the inferior petrosal sinus, are discussed. We also discuss the reliability of SjO2 monitoring in the present CCSF case.

Detection of early ischemia in severe head injury by means of arteriovenous lactate differences and jugular bulb oxygen saturation. Relationship with CPP, severity indexes and outcome. Preliminary analysis.

UNLABELLED: Early ischemia may be highly relevant in patients with severe head injuries. The aims of the study were: 1) to define if abnormal arteriovenous lactate difference (AVDL) and jugular bulb oxygen saturation (SjO2) are found in the early 24 hrs post injury; 2) to compare if abnormalities of SjO2 and of AVDL were associated with a specific typology of severity indexes and outcome; 3) to detect any association between abnormal AVDL and SjO2 with levels of cerebral perfusion pressure (CPP). The study involved 29 patients, with CPP, AVDL and SjO2 measured within 24 hours post-injury. RESULTS: 1) Abnormal AVDL was found in 21% while abnormal SjO2 was detected in 38% of the patients; 2) abnormal AVDL was associated with cases of most severe injury; 3) CPP level below 60 mmHg was associated with abnormal AVDL and SjO2. Low CPP appeared to be the most likely measurable cause of early ischemia. Abnormalities of AVDL appeared to be more sensitive, than SjO2, with regard to detection of the most severe cases.

Evolving lesions in traumatic subarachnoid hemorrhage: prospective study of 110 patients with emphasis on the role of ICP monitoring.

We have consecutively studied 110 patients with traumatic subarachnoid hemorrhage (tSAH) on the first Computed Tomography (CT) scan (obtained in each case within 3 hours from injury). The only exclusion criteria were brain death on admission, and severe hypotension due to extracranial injuries. All CTs were reviewed by one of us and the "worst" CT examination was determined. We defined the worst CT examination as that showing the most extensive degree of parenchymal-associated damage. Intracranial pressure was monitored in 25 severely head injured patients. Seventy-four patients (66%) showed an evolution from the initial CT scan (worst CT not corresponding to the admission CT). The outcome was favorable in 53 cases (73%) of patients with evolving lesions and in 32 cases (89%) with non evolving lesion. In the 25 severely head injured patients, Intra-cranial Pressure (ICP) monitoring (in combination with scheduled repeat CT scan) was helpful to identify the timing of the worst parenchymal damage and of surgery in those patients with an initial normal intracranial pressure in spite of an evolving lesion.

Mixed dishomogeneous hemorrhagic brain contusions. Mapping of cerebral blood flow.

The aim of the study was to verify whether regional cerebral blood flow (rCBF) was distributed centrifugally in traumatic hemorrhagic contusions with multiple cores within an oedematous area. Seventeen traumatic brain contusions, from 14 patients with severe head injury (GCS < 9), were analyzed during 39 Xenon-enhanced computerized tomography (Xe-CT) studies. The CBF was measured in 3 concentric regions of interest (ROls): the hemorrhagic core, the intracontusional oedematous low density area and a 1 cm rim of pericontusional normal-appearing brain tissue surrounding the contusion. Differences between rCBFs in the three ROIs were found (p < 0.0001). rCBF in both the hemorrhagic core (21.4 +/- 19.4 ml/ 100gr/min) and the intracontusional low density area (28.4 +/- 19 ml/100gr/min) were lower than rCBF in pericontusional normal-appearing area (41.9 +/- 16 ml/100gr/min) (p < 0.0001). No significant differences were found between rCBF measured in the hemorrhagic core and intracontusional low density area (p = 0.184). Our study suggests that in the mixed density contusions with multiple hemorrhagic cores, the CBF is concentrically distributed, improving from the core to the periphery.

Induced acute arterial hypertension and regional cerebral flow in intracontusional low density area.

Traumatic brain contusions have been associated with regional ischemia. We aimed to measure the effect of induced supra-normal values of cerebral perfusion pressure (CPP) on regional cerebral blood flow (rCBF) in the intracontusional low density area surrounding the contusional hemorrhagic core. In 7 severely head injured patients (GCS < or = 8) harbouring a contusion larger than 2 cm, the rCBF levels were measured, by means of Xenon-enhanced CT, in: 1) the intracontusional low density area: 2) contralaterally, in a normal brain symmetric area. CBF studies were performed at a baseline CPP of 65.3 mmHg +/- 7 and after 20 minutes of norepinephrine-induced CPP supernormal values (88.3 mmHg +/- 10.5) (p = 0.0013). A "paradoxical" reduction of rCBF levels was observed in both the intracontusional low density area (p = 0.07) and the contralateral "normal" area (p = 0.08). In particular, this decrease of rCBF in the intracontusional low density area (-25.7 + 10 ml/100gr/min) (p = 0.0009) was present in only 4 cases, having a mean rCBF at baseline of 25 +/- 16 ml/100gr/min. In the remaining 3 cases in which rCBF at baseline was abnormally low (12 +/- 7 ml/ 100gr/min), rCBF values improved slightly (3.6 +/- 2 ml/100gr/min) (p = 0.61). An acute increase of CPP seems to marginally affect rCBF in the intracontusional low density area having critically reduced initial values, but may greatly reduce rCBF in subjects starting from non-critical baseline values.

Do different dialytic techniques have different atherosclerotic and antioxidant activities?

To compare the chronic effect of several dialytic techniques (bicarbonate dialysis, BHD; acetate free biofiltration, AFB; hemodiafiltration, HDF; paired filtration dialysis, PFD) on atherosclerosis and antioxidant activity, three different indices were created. The first (atherosclerotic index = AI) is formed using the sum of three plasma substances: MDA, Hcy, and Cys (malondialdehyde, homocysteine, cysteine). The second (antioxidant activity index = AOAI) is the sum of five erythrocyte (E) parameters: E-GSH, GPx, CAT, SOD, GR (E-glutathione, E-glutathione peroxidase, E-catalase, E-superoxide dismutase, E-glutathione reductase). The third (defense index = DI) is derived from the previous two: (AOAI - AI). The indices were so expressed as AI in mmol/L, AOAI in U/g hemoglobin (Hb), and DI in arbitrary units. These indices were calculated in 20 controls and 51 chronic HD patients (26 female, 25 male) before, during, and after the first session of the week. HD patients were divided according to their dialytic technique: BHD, n = 35; AFB, n = 5 patients; HDF, n = 7 patients; or PFD = 4 patients. All patients had been treated with a given technique for at least 12 months, before entering the study. As expected, HD patients had AI values higher than controls, both before and after the session, with a mean value of 541 (before) and 331 (after), whereas controls had a mean value of 205. The AOAI was lower than controls, both before and after the session, the mean value being 1,122 (before) and 1,582 (after), that of controls being 2,424. In all cases, PFD gave the best "acute" results; at the end of a PFD session, near normal values of AI, AOAI, and DI (defensive index = AOAI - AI) were obtained.

Pharmacologic data and technical feasibility of intraperitoneal doxorubicin administration.

Seventy intraperitoneal administrations of doxorubicin were performed in 12 patients with malignant disease in the abdominopelvic space. Peritoneal and hematologic drug levels were measured by fluorimetric assay. A first-order decline in the peritoneal level was determined (T 1/2 96 +/- 18 min), with a mean drug absorption of 84% in 4 h (range 40-96%) and a mean ratio of a peak dialysate/peak serum level of 111 (range 12-390). Gastrointestinal toxicity was common and peritoneal phlogosis occurred twice. The doxorubicin level and the time of peritoneal exposure seem to be critical factors for major local toxicity. At a moderate concentration doxorubicin can be intraperitoneally administered, but its usefulness is probably confined to patients with minimal abdominal disease.

Acute poisoning with methidathion: a case.

An acute poisoning in a 50-year-old man who ingested approximately 6.2 g of the phosphorus ester methidathion is described. The patient was treated with three haemoperfusions 23, 44 and 115 h after ingestion, with continuous gastric lavage, atropine and pralidoxime administration and with prolonged mechanical ventilation. Haemoperfusion was an ineffective epuration technique since it removed only 0.22% of the ingested methidathion. The clinical course wavered because of a probable redistribution of phosphorus ester from fat to blood. A plasma level higher than 100 micrograms l-1 was associated with the most serious phases. Methidathion was present in the plasma until the sixth day, in the urine until the seventh and in the gastric juice until the eighth. Its absence in the fat biopsy made on the tenth day was an aid to therapy. The phosphorus ester did not inhibit lymphocyte neuropathy target esterase (NTE), neither did it induce development of delayed polyneuropathy.

[Alcohol consumption and coronary disease in men]. / Consumo di alcol e malattia coronarica nell'uomo.

It has been recently suggested by many epidemiological studies, and emphasized by a nonspecialistic press, that a moderate alcohol intake may exert a protective role in coronary heart diseases. In our study, by means of a questionnaire, the consumption of alcohol in 100 male patients, less than 70 years old, affected by myocardial infarction and/ or angina pectoris, has been evaluated during a period before and after the admission to our Coronary Care Unit. On the basis of their alcohol intake, patients were divided into five categories: abstainers (8%), daily intake lower than one drink (7%), between one and two drinks (8%) between three and four drinks (46%) and equal or higher than five drinks (31%). In the light of these results, we suggested that, in our region (a country area in the north-east of Italy), there are higher levels of ethanol intake compared to those reported by other authors, that these parameters are only slightly modified by the occurrence of coronary heart diseases and that alcohol consumption, although low and moderate, must be therefore emphasized with extreme caution.