Immunology highlights at high altitude: review of the fourth EAACI-GA2LEN Davos Meeting.
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Altitude↗
Biomedical subjects
F Alessandrini
Publications and source records attributed to F Alessandrini.
Reversible choreoathetosis as the early onset of HIV-encephalopathy.
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AIDS Dementia Complex↗
Gamma knife radiosurgery in brain metastases from testicular tumors.
To our knowledge, there are no published reports on the effectiveness of radiosurgery in the management of brain metastases from testicular nonseminomatous germ cell tumor. The authors evaluate the results of gamma knife (GK) treatment in three patients with these unusual intracranial lesions. Between April 1995 and July 2001, three patients with brain metastasis from testicular nonseminomatous germ cell tumor underwent adjuvant radiosurgery at our department. The primary tumor had been surgically removed in all cases. At diagnosis, one patient was stage IB and two were stage III poor risk. Chemotherapy and whole brain radiotherapy were administered before radiosurgery in all cases. Pre-GK radiotherapy was administered with a daily fraction dosage of 1.8-2.0 Gy. The indications for radiosurgery were tumor volume <20 cm3, microsurgery too risky, refusal of surgery. All the lesions were located in eloquent brain areas. Post-GK high-dose chemotherapy with autologous peripheral-blood stem-cell rescue was administered in two cases due to systemic recurrence of the disease. All patients are still alive with a median and mean follow-up period after radiosurgery of 63 and 68.3 mo, respectively. They had no neurological deficits at the latest examination. Neuroradiological follow-up invariably showed tumor growth control (complete response in two cases and partial response in one) with typically delayed post-radiosurgical imaging changes (transient in two cases and long-lasting in one). In conclusion, GK seems to be highly effective and safe in brain metastases from testicular nonseminomatous germ cell tumor. In cases with diffuse metastatic brain involvement, the whole brain radiotherapy preceding radiosurgery should be delivered with 1.8 Gy daily fraction to prevent the risk of long-lasting post-radiosurgical imaging changes.
Adolescent↗
Effects of inhaled CdO particles on the sphingolipid synthesis of rat lungs.
Surfactant lipids of the alveolar space protect the lung from various environmental stimuli. We investigated the influence of ultrafine (UF) CdO particles inhalation on two key enzymes involved in lung sphingolipid metabolism, serine palmitoyltransferase (SPT), and sphingomyelinase (SMase). Rats inhaled either 0.63 mg UF-CdO/m(3) for 6 h (group 1), or 1.08 mg UF-CdO/m(3) 12 h/day for 10 days (group 2). Two corresponding control groups inhaled filtered clean air. Additional rats intratracheally instilled with lipopolysaccharide (LPS) were used as positive controls. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) of lung tissue showed a significant increase in the level of SPT mRNA (LCB2 subunit) expression in group 2 compared to the corresponding controls (p <.01). Group 1 and LPS were not statistically different from control. No alteration in the mRNA level of SMase was detected in any exposure group. The immunohistochemical analysis showed that SPT (LCB2 subunit) localization was stronger in the alveolar type II cells of group 2 lungs compared to the corresponding controls. These results were correlated with alterations in BALF cellular and biochemical parameters and lung morphology. Since SPT is the key enzyme for de novo sphingolipid synthesis in lung surfactant and SMase is responsible for sphingomyelin catabolism, we can postulate that high-dose UF-CdO exposure for 10 days induces an increase in sphingolipid synthesis in the type II cells of rat lungs that would not be promptly followed by its degradation.
Acyltransferases↗
Syringomyelia following Listeria meningoencephalitis: report of a case.
A case of symptomatic syringomyelia which appeared six years after Listeria meningoencephalitis is described. Chronic spinal arachnoiditis, as shown by standard MRI and dynamic phase contrast (PC) cine-MRI, may occur after spinal infection and is likely the cause of syringomyelia. To our knowledge, there are no previous reports of delayed spinal complications following Listeria monocytogenes infection. The possibility of developing syringomyelia should be always considered in any patient with a history of central nervous system infection.
Alcoholism↗
Gamma knife radiosurgery in the management of arteriovenous malformations of the Basal Ganglia region of the brain.
OBJECTIVES: The authors report the results of gamma knife (GK) radiosurgery on a clinical series of selected patients with basal ganglia arteriovenous malformations (BGAVMs) in the brain. Clinical, epidemiological, anatomical and functional characteristics of BGAVMs and of supratentorial cortical AVMs are comparatively analyzed, and their influence on radiosurgical outcome is discussed. METHODS: At our Department, 33 BGAVMs (21 with FU > 2 years) and 209 cortical AVMs (110 with FU > 2 years) with a radiosurgical volume </= 10 cc were treated with GK between February 1993 and July 2001. Mean age, male/female ratio (M/F), and incidence of haemorrhagic onset in the two subgroups of patients were as follows: 25.5 years (5 - 62 years), 16 M/17 F, and 30/33 (91%) in BGAVMs; 34.4 years (8 - 74 years), 124 M/85 F, and 107/209 (51%) in cortical AVMs. Statistical analysis performed using the contingency table method and deviance analysis according to generalized linear models showed that the differences in age and incidence of haemorrhagic onset were highly significant. RESULTS: The rates of complete obliteration, permanent morbidity, bleeding/rebleeding during the latency period, and unsuccessful embolisation attempts in the two subgroups of patients were as follows: 81%, 4%, 8%, and 41.7%, respectively, in BGAVMs; 85.5%, 2%, 2%, and 2% in cortical AVMs. Statistical analysis did not show any significant difference between the two subgroups of patients in the rates of complete obliteration, permanent morbidity, or latency period bleeding/rebleeding, while difference in failed embolization rates resulted to be highly significant (P = 0.00003). CONCLUSIONS: In our experience, the different clinical, epidemiological and anatomico-functional characteristics of BGAVMs and cortical AVMs do not seem to influence the radiosurgical outcome, since complete obliteration and permanent neurological sequelae rates were very similar in these two subgroups of patients. GK may be considered the first choice treatment modality for BGAVMs with < 10 cc volume, since it offers a very high cure rate, very low permanent morbidity, and zero mortality. Although haemorrhagic onset is much more frequent in BGAVMs than in cortical AVMs, the difference between the bleeding/rebleeding rates in the two subgroups of patients during the latency period is not statistically significant, and seems to be limited to the first year after GK.
Adolescent↗
Clinical and angiographic effects of chronic calcium channel blocker therapy continued beyond first postoperative year in patients with radial artery grafts: results of a prospective randomized investigation.
BACKGROUND: This study was conceived to elucidate the clinical and angiographic effects of chronic calcium channel blocker therapy (CCCBT) continued after the first postoperative year in patients in whom the radial artery (RA) was used for myocardial revascularization. METHODS AND RESULTS: Patients who received RA grafts at our institution and who at 1 year had no scintigraphic evidence of ischemia in the RA territory or angiographic evidence of RA malfunction (n=120) were randomly assigned to continue (n=63) or suspend (n=57) the CCCBT with diltiazem (120 mg/d). After 5 years, all patients were reassessed clinically and by stress myocardial scintigraphy, and 87 of them (45 from the continued group that continued CCCBT and 42 from the group that suspended CCCBT) were restudied angiographically. No differences regarding either the clinical and scintigraphic results or the RA angiographic status were demonstrated between the 2 groups. CONCLUSIONS: After the first postoperative year, the continuation of CCCBT does not affect RA graft patency or clinical and scintigraphic results.
Calcium Channel Blockers↗
Should severe monolateral asymptomatic carotid artery stenosis be treated at the time of coronary artery bypass operation?
OBJECTIVE: The optimal treatment of severe monolateral asymptomatic carotid artery stenosis (SMACS) in patients undergoing coronary artery bypass grafting (CABG) is still controversial. MATERIALS AND METHODS: This study is based on the in-hospital and mid-term (>5 years) clinical results of a cohort of 139 consecutive CABG patients with SMACS operated at our Institution between January 1989 and December 1995. In the first 73 patients (no carotid surgery group), the SMACS was left untouched at the time of coronary surgery, whereas in the remaining 66 (carotid endoarterectomy group), the carotid stenosis was treated either immediately before or concomitantly with the CABG procedure (depending on the severity of the anginal symptoms). RESULTS: The overall preoperative characteristics of the patients were comparable. The in-hospital results were similar between the two groups with regard to mortality, stroke and major postoperative complications. However, at mid-term follow-up, significantly more patients of the no carotid surgery group suffered cerebral events (transient or permanent) ipsilateral to the SMACS or the lesion had to be operated on. CONCLUSIONS: The concomitant treatment (either staged or simultaneous) of SMACS at the time of CABG does not influence the in-hospital results, but confers significant neurological protection during the years after the operation.
Aged↗
The level of prosaposin is decreased in the skin of patients with psoriasis vulgaris.
Ceramides are the most abundant lipids constituting the intercellular matrix of the skin stratum corneum and their critical role in skin homeostasis has been extensively documented. Their concentration in the skin highly depends on the rate of availability of the enzymes involved in ceramide generation. The aim of this study was to investigate whether the concentration of prosaposin was altered in the skin of patients with psoriasis vulgaris. Prosaposin, the precursor of saposins (sphingolipid activator proteins), was measured in lesional and nonlesional skin of psoriatic patients and in normal skin from surgical patients, both at the mRNA and at the protein level. Densitometric analysis of reverse transcriptase-polymerase chain reaction bands separated by gel-electrophoresis showed a progressive decrease of prosaposin mRNA expression in nonlesional and lesional psoriatic skin, being substantially decreased in lesional psoriatic skin compared with normal control skin. Immunohistochemical analysis showed a significant decrease of prosaposin level in the stratum corneum of psoriatic lesional skin (both in active-type and in chronic-type plaque) compared with nonlesional and with normal skin (p < 0.01), and in psoriatic nonlesional skin compared with normal control (p < 0.05). Immunolocalization of sphingomyelinase in lesional and nonlesional psoriatic skin showed a decrease in the level of this enzyme in the stratum corneum of psoriatic lesional, compared with nonlesional skin. These results support the concept that disturbance of epidermal barrier function caused by derangement in ceramide generation can be crucial for the development of psoriatic skin diseases.
Adult↗
Gamma knife radiosurgery in meningiomas of the posterior fossa. Experience with 62 treated lesions.
OBJECTIVES: This study was undertaken to assess the role of the gamma knife (GK) in the treatment of meningiomas of the posterior cranial fossa (PCF) and to statistically analyze the predictability of arbitrarily-selected prognostic factors in such treatment. METHODS: From February 1993 to November 1998, 57 patients underwent GK treatment for 62 meningiomas of the PCF (19 M/38 F; average age, 57.5 years, ranging from 25 - 82 years). Tumor sites included: foramen jugular-petrous bone (26/62), petroclival (23/62), cerebellar convexity (6/62), tentorium (6/62), and foramen magnum (1/62). Single lesions were treated in 44/62 cases while meningiomatosis was treated in the remaining 18. Post-operative residual or recurrent tumor was found in 27/62 patients and, in 7/27, histology documented characteristics of biological aggressiveness (GII/III). Indications for radiosurgery included: advanced age, high operative risk, tumor volume < 20 ml, inoperable or refused for additional surgery. The prognostic factors statistically analyzed included: meningiomatosis (yes/no), radiosurgery as primary or adjuvant treatment, GI vs. GII/III histology, and tumor volume (< or = 5 ml vs. > 5 ml). RESULTS: The observation periods varied from 6 to 64.3 months (median 28.7 months). At the end of the study, 53/57 patients were alive and reported to be in stable or improved neurological condition. The cause of death for the remaining 4 patients included: 2 deaths associated with tumor progression, while 2 died due to causes unrelated to the disease. Neuroradiological evaluation documented the disappearance or reduction of the meningioma mass in 34/62 (55 %) cases, a stable imaging picture in 25/62 (40 %), and a progression only in 3/62 (5 %). To date, there have been no reported cases of post-GK permanent morbidity or mortality. Side effects observed were of a transient nature due to post-radiosurgical edema (6.5 %). With regard to statistical analysis, the only factor to appear to significantly influence efficacy of radiosurgery for tumor growth control (TGC) was the biological nature of the meningioma (chi(2) = 2.708). The presence of meningiomatosis, SR as a primary or adjuvant treatment nor tumor volume were shown to statistically influence tumor behavior after GK. CONCLUSIONS: The excellent results obtained for TGC with minimal associated side effects suggest that GK is an effective therapeutic tool also for treatment of PCF meningiomas.
Adult↗
The unclampable ascending aorta in coronary artery bypass patients: A surgical challenge of increasing frequency.
BACKGROUND: The unclampable ascending aorta (UAA) is a condition increasingly encountered during CABG procedures. We report our experience with CABG patients with UAA and place particular emphasis on the preoperative diagnosis and surgical management. METHODS AND RESULTS: UAA was diagnosed in 211 of 4812 consecutive CABG patients (4.3%). On the basis of the chest radiograph, echocardiogram, and coronary angiograph, a preoperative diagnosis was achieved in only 58 patients (27.4%). An age of >70 years, diabetes, smoking, unstable angina, diffuse coronaropathy, and peripheral vasculopathy were all predictors of UAA. Patients were treated with hypothermic ventricular fibrillation (no-touch technique n=129) or beating heart revascularization (no-pump technique n=82) depending on the possibility of founding an arterial cannulation site. The overall in-hospital mortality rate was 2.8% (6 of 211) with no differences between the 2 surgical strategies. The no-touch technique was associated with a greater incidence of neurological complications (stroke and transient ischemic attack), renal insufficiency, and stay in the intensive care unit and hospital. However, at midterm follow-up, more patients of the no-pump group had ischemia recurrence. CONCLUSIONS: A preoperative diagnosis of UAA is achievable only in a minority of patients, which highlights the necessity revising the current diagnostic protocols. The use of the no-touch technique is associated with an high perioperative risk but a superior possibility of complete revascularization, whereas adoption of the no-pump strategy ensures a smoother postoperative course at the expense of an higher incidence of ischemia recurrence.
Aged↗
Cerebrospinal fluid flow dynamics study in Chiari I malformation: implications for syrinx formation.
Cerebrospinal fluid (CSF) flow abnormalities are known to be present in Chiari I malformation and to underlie the origin and progression of associated syringomyelia. The incidence of syrinx formation, however, is variable for unknown reasons. The aim of this study was to investigate whether differences in CSF flow dynamics in patients with Chiari I malformation may account for the different clinical and radiological presentation. Presurgical and postsurgical phase-contrast magnetic resonance imaging investigations were prospectively conducted in 47 adult patients with symptomatic Chiari I malformation. Patients were divided into two groups according to the presence (32 cases) or absence (15 cases) of syrinx. Cerebrospinal fluid flow patterns were evaluated at four regions of interest: prebulbar cistern, foramen magnum, and the ventral and dorsal spinal subarachnoid spaces at the C-5 level. A temporal analysis of CSF flow waveforms was performed with measurement of cranial- and caudal-directed flow durations. All patients underwent a craniocervical decompressive procedure. Preoperatively, a prolonged caudal- directed (systolic) flow pattern was observed in patients with syringomyelia, as compared with normal control values obtained in 15 healthy volunteers. Conversely, a decreased systolic duration was observed in Chiari I patients who had malformation without syrinx. These trends were not statistically significant because of the considerable degree of overlap with the control values recorded in both groups. Additional comparison of the observed preoperative values obtained in patients with and those without syringomyelia indicated that the difference in systolic flow duration was significant at the ventral spinal subarachnoid space level (p = 0.003) and remarkable at the other levels, although not reaching statistical significance. Cerebrospinal fluid flow was minimal or absent at the foramen magnum (dorsal aspect) due to tonsillar herniation, precluding reliable quantitative measurement at this level. There was no evidence of communication between the fourth ventricle and syrinx in any case. Postoperatively, unobstructed CSF flow was recorded across the enlarged foramen magnum and into the artificial cisterna magna in all patients. A gradual restoration of near-normal flow patterns was observed in both groups. Inside the syrinx, fluid motion gradually tapered, no longer being detectable in 12 patients (37.5%) 1 year postsurgery. In patients with Chiari I malformation and associated syringomyelia different CSF flow patterns were demonstrated as compared with patients in whom syrinx was absent. Analysis of this study's findings supports the hypothesis that in Chiari I malformation an elongated systolic flow may prolong the condition of increased spinal subarachnoid pressure caused by the junctional obstruction, thus favoring CSF penetration into the spinal cord. It may be also proposed that a shortened systolic flow may be insufficient to maintain a hypertensive condition for enough time to induce syrinx formation.
Adult↗
Identification of immunological relevant phenotypes in ENU mutagenized mice.
The immunology screen focuses on the identification of novel gene products involved in the mammalian immune response and on the establishment of mouse models for immunological disorders. For this purpose, high throughput and semi-automated techniques were developed and optimized for low cost per sample and reproducibility. All assays are designed to be nonconsumptive and are based on peripheral blood or direct PCR amplification.
Animals↗
Topical use of tranexamic acid in coronary artery bypass operations: a double-blind, prospective, randomized, placebo-controlled study.
OBJECTIVES: We sought to investigate the effect of topical application of tranexamic acid into the pericardial cavity in reducing postoperative blood loss in coronary artery surgery. METHODS: A prospective, randomized, double-blind investigation with parallel groups was performed. Forty consecutive patients undergoing primary coronary surgery were randomly assigned to group 1 (tranexamic acid group) or group 2 (placebo group). Tranexamic acid (1 g in 100 mL of saline solution) or placebo was poured into the pericardial cavity and over the mediastinal tissues before sternal closure. The drainage of mediastinal blood was measured hourly. RESULTS: Chest tube drainage in the first 24 hours was 485 +/- 166 mL in the tranexamic acid group and 641 +/- 184 mL in the placebo group (P =.01). Total postoperative blood loss was 573 +/- 164 mL and 739 +/- 228 mL, respectively (P =.01). The use of banked donor blood products was not significantly different between the two groups. Tranexamic acid could not be detected in any of the blood samples blindly collected from 24 patients to verify whether any systemic absorption of the drug occurred. There were no deaths in either group. None of the patients required reoperation for bleeding. CONCLUSIONS: Topical application of tranexamic acid into the pericardial cavity after cardiopulmonary bypass in patients undergoing primary coronary bypass operations significantly reduces postoperative bleeding. Further studies must be carried out to clarify whether a more pronounced effect on both bleeding and blood products requirement might be seen in procedures with a higher risk of bleeding.
Administration, Topical↗
Genome-wide, large-scale production of mutant mice by ENU mutagenesis.
In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper, leads to a significant increase in the number of mouse models available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).
Animals↗
Exacerbation of chronic large plaque psoriasis associated with Olanzepine therapy.
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Antipsychotic Agents↗
Coronary angiodysplasia of epicardial and intramural vessels.
A case of coronary angiodysplasia combining large aneurysms of epicardial arteries with diffuse malformation of intramural vessels is reported. Clinical presentation may mimic a vascularized cardiac tumor. Although leaking of the aneurysms in the pericardial space may occur, this entity seems to have a benign prognosis not requiring surgical repair.
Adult↗
Individualized surgical strategy for the reduction of stroke risk in patients undergoing coronary artery bypass grafting.
BACKGROUND: This study was designed to evaluate the efficacy of a protocol of systematic screening of the ascending aorta and internal carotid arteries and individualization of the surgical strategy to the ascending aorta and internal carotid arteries status in reducing the stroke incidence among patients undergoing coronary artery bypass grafting. METHODS: On the basis of a pre- and intraoperative screening of the ascending aorta and internal carotid arteries, 2,326 consecutive patients undergoing coronary artery bypass grafting were divided in low, moderate, and high neurologic risk groups. In the high-risk group dedicated surgical techniques were always adopted and the reduction of the neurologic risk was considered more important than the achievement of total revascularization. RESULTS: The incidence of perioperative stroke in the high-risk group was similar to those of the other two groups (1.1 versus 1.3 and 1.1%, respectively; p = not significant); however, angina recurrence was significantly more frequent in the high-risk group. CONCLUSIONS: The described strategy allows a low rate of perioperative stroke in high-risk patients undergoing coronary artery bypass grafting. Whether the reduction of the neurologic risk outweighs the benefits of complete revascularization remains to be determined.
Carotid Artery, Internal↗