Reirradiation of salivary gland tumors with carbon ion radiotherapy at CNAO.

AIMS: To report oncologic and functional outcomes in terms of tumor control and toxicity of carbon ion radiotherapy (CIRT) in reirradiation setting for recurrent salivary gland tumors at CNAO. METHODS: From November 2013 to September 2016, 51 consecutive patients with inoperable recurrent salivary gland tumors were retreated with CIRT in the frame of the phase II protocol CNAO S14/2012C for recurrent head and neck tumors. RESULTS: Majority of pts (74.5%) had adenoid cystic carcinoma, mainly rcT4a (51%) and rcT4b (37%). Median dose of prior photon based radiotherapy was 60 Gy. Median dose of CIRT was 60 Gy [RBE] at a mean of 3 Gy [RBE] per fraction. During reirradiation, 19 patients (37.3%) experienced grade G1 toxicity, 19 pts (37.3%) had G2 and 2 pts (3.9%) had G3. Median follow up time was 19 months. Twenty one (41.2%) patients had stable disease and 30 (58.8%) tumor progression at the time of last follow up. Furthermore, 9 (18%) patients had G1 late toxicity, 19 (37%) had G2 and 9 (17. 5%) had G3. Using the Kaplan Meier method, progression free survival (actuarial) at one and two years were 71.7% and 52.2% respectively. Estimated overall survival (actuarial) at one and two years were 90.2% and 64%, respectively. CONCLUSIONS: CIRT is a good option for retreatment of inoperable recurrent salivary gland tumors with acceptable rates of acute and late toxicity. Longer follow up time is needed to assess the effectiveness of CIRT in reirradiation setting of salivary gland tumors.

Rescue of a living donor with liver transplantation.

Postoperative liver failure is a rare complication after living donor liver resection. This is a case report of a 22-year-old healthy donor who was rescued with liver transplantation 11 days after right hemihepatectomy. Nine months later the patient is alive, and has fully recovered from his multiple organ failure. According to a review of the literature, there are four additional living liver donors, who received a liver transplant. Our own patient is the only survivor, so far. This case demonstrates that even in supposedly healthy living donors postoperative complications cannot be completely prevented. Although liver failure is rare in these patients, timely transplantation may need to be considered as the only life-saving treatment.

Neurologic complications of the Novacor left ventricular assist device.

BACKGROUND: The left ventricular assist device (LVAD) is a bridging mechanism for patients with severe heart failure to remain viable until heart transplantation. The rate of cerebral embolism has been reported as high as 47% in some studies but the rate of other neurologic complications in patients with LVADs is not known. METHODS: Retrospective chart review of all patients who had LVADs implanted at our hospital from September 1993 until September 1997. Complications from the time of implantation until heart transplantation or death and functional outcome were assessed. RESULTS: Twenty-three patients had LVADs placed in the four-year period. Of 23 patients, 9 had neurologic complications after placement of the LVAD. These included four strokes, three seizures, and two cases of delirium. The 3 patients with seizures all died from multiorgan failure. All of the patients with strokes received a transplant. One patient with delirium died from multiorgan failure and another received a transplant. The most devastating medical complication was renal failure, which occurred in 7 patients and was associated with 100% mortality. All surviving patients with neurologic complications went on to transplant and good functional outcome. CONCLUSIONS: Neurologic complications are common in patients with LVADs, occurring in 9 out of 23 patients in our series. Seizures are a poor prognostic indicator and were associated with 100% mortality. Strokes did not have a negative impact on outcome. Patients with delirium had a mixed outcome, which reflects the multifactorial nature of delirium. Further study needs to be done to limit the neurologic complications associated with LVADs and further improve outcomes.

Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans.

This study developed methods and determined the impact of influenza vaccination on elderly persons in 3 large health plans: Kaiser Permanente Northwest, HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998 seasons were extracted from administrative databases. Subjects were health plan members > or = 65 years old. Comorbid conditions collected from the preceding year were used for risk adjustment with logistic regression. The virus-vaccine match was excellent for year 1 and fair for year 2. Both years, during peak and total periods, vaccination reduced all causes of death and hospitalization for pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for the same periods. These results show that all elderly persons should be immunized annually for influenza. The methods used in this study are an efficient cost-effective way to study vaccine impact and similar questions.

The removal of low level inorganics via electrogenerated hydrogen peroxide in the presence of catalytic amounts of Fe2+.

Low level phosphites and hypophosphites were completely converted into phosphates, via hydrogen peroxide generated by cathodic reduction of oxygen in acidic aqueous medium at a reticulated vitreous carbon electrode, in the presence of little amounts of Fe2+. The contemporary regeneration of Fe2+ by cathodic reduction of Fe3+, produced by the well known Fenton reaction, furnishes an excellent way to continuously produce little amounts of the Fenton reactive and, as a consequence, of the powerful oxidant hydroxyl radical HO.. The best conditions for the complete removal of phosphorous as phosphites and hypophosphites are reported.

In vitro evaluation of antioxidant activity by electrophoresis and high performance liquid chromatography.

Two methods for the analysis of antioxidants, based on polyacrylamide gel electrophoresis (PAGE) and gel permeation high performance liquid chromatography (HPLC) were developed. Both of them exploit the variations of the signal (band or peak) given by human serum albumin (0.2% w/v in 100 mM sodium phosphate pH 7) upon oxidation with hypochlorite (1% of a solution containing 4% active Cl), quantitatively determined by densitometric analysis or peak integration. Based on such changes, two formulas were defined which allowed the determination of the antioxidant activity of ascorbic acid (EC(50,PAGE)=4.8x10(-4) M, EC(50,HPLC)=3.6x10(-4) M), glutathione (EC(50,PAGE)=1.5x10(-4) M, EC(50,HPLC)=2.0x10(-4) M) and melatonin (EC(50,PAGE)=5.2x10(-4) M, EC(50,HPLC)=3.2x10(-4) M), chosen as reference compounds. A good correlation was found between the activities of these substances in the two assays, which are also in good agreement with literature data, indicating that the two methods are essentially equivalent. These assays could be useful for the screening of new antioxidant drugs for pathological conditions such as cataract, rheumatic diseases, atherosclerosis and Alzheimer's disease.

Dot-and-fleck retinopathy in Alport syndrome caused by a novel mutation in the COL4A5 gene.

PURPOSE: To describe an unusual form of dot-and-fleck retinopathy in a slower progressive form of X-linked Alport syndrome, caused by a novel missense mutation in the COL4A5 gene. METHOD: Ophthalmic examination, polymerase chain reaction, and single-strand conformational polymorphism analysis of genomic DNA were performed in the proband. RESULTS: Ophthalmoscopy revealed classic dot-and-fleck retinopathy but located in an unusual site. A novel COL4A5 gene mutation changing glycine to cysteine at 177 was identified. CONCLUSIONS: Although there is no correlation between mutation site and the resulting phenotype in Alport syndrome, our findings suggest that further novel mutations and different ocular manifestations may be associated with Alport syndrome.

The effect of psychological intervention on patients' long-term adjustment to the ICD: a prospective study.

This study prospectively examined the role of cognitive behavioral therapy (CBT) in (1) alleviating psychological and somatic distress, and (2) lowering arrhythmic events requiring shocks. Forty-nine of 61 consecutive patients were randomized into therapy (CBT, n = 25) or no therapy (NT, n = 24) and completed a battery of self-report questionnaires at baseline and at 9-month follow-up. CBT was administered at preimplant, predischarge, and at seven routine follow-up visits. Patients were 65 +/- 10 years old, 65% were men, and 92% Caucasian. Eighteen (72%) CBT patients and 18 (75%) NT patients were retained at follow-up. Compared to CBT patients, NT patients reported higher levels of depression (P = 0.046), more anxiety (P = 0.013), more psychological distress (P = 0.015), poorer overall adjustment (P = 0.009), and poorer sexual functioning (P = 0.003). Mean number of shocks did not differ between the CBT and NT groups (2.85 vs 2.30, respectively); however, more patients in the CBT group (61%) than the NT group (33%) received shocks (P = 0.070). At follow-up, a subgroup analysis revealed that the significant differences observed between the CBT and NT groups were attributable to the patients who received shocks in both groups. In conclusion, CBT was associated with decreased depression, decreased anxiety, and increased adjustment for ICD recipients, particularly among those patients receiving shocks. CBT can be administered effectively at routine follow-up visits or transtelephonically with little added inconvenience to the ICD recipient.

Cardiac ventricular support. Considerations for psychiatry.

Cardiac ventricular support is fostering additional roles for psychiatric consultation with this vulnerable end-of-life cardiac group. Incidence of premorbid and postsurgical psychiatric disorders (Axis I), psychotropic use, neurologic events, and mortality was obtained for 21 Novacor left-ventricular assist system patients prospectively and 13 Abiomed left/right ventricular-assist device patients retrospectively. This fragile patient population and their families warrant involvement for psychiatry because of the extreme conditions and consequences associated with mechanical cardiac assistance. The authors address psychiatric morbidity and neurobehavioral modifications associated with ventricular support.

Use of the MMPI and MMPI-2 in patients being evaluated for cardiac transplant.

The MMPI and MMPI-2 have been used extensively in the study of personality correlates in various coronary populations. It has been hypothesized that personality variables are associated with various clinical outcomes, such as quality of life, morbidity, and mortality; however, no data are available in a cardiac transplant sample. This study presents descriptive MMPI and MMPI-2 data for male and female patients awaiting cardiac transplant. Analyses of differences in MMPI-2 depression scales between cardiomyopathy groups for 366 men and 99 women were performed. Significant differences were found between ischemic and nonischemic male patients.

Soluble vascular cell adhesion molecule-1 as a biohumoral correlate of atherosclerosis.

Vascular cell adhesion molecule-1 (VCAM-1) is a protein expressed on the surface of activated endothelial cells and expressed in early atherosclerosis. Because part of the protein is shed in the circulation and can be detected in peripheral plasma [soluble (s) VCAM-1], we hypothesized that sVCAM-1 may be a circulating marker of the presence and severity of atherosclerosis in humans. We selected 11 patients with essential hypertension plus peripheral vascular disease (PVD) and matched them for age, gender, body mass index, and smoking habits with 11 patients with uncomplicated essential hypertension (UH) and 11 healthy controls. We evaluated plasma concentrations of sVCAM-1 along with those of the soluble form of two other endothelial leukocyte adhesion molecules [sE-selectin and s-intercellular adhesion molecule-1 (sICAM-1)] and other markers of endothelial dysfunction/ damage [s-thrombomodulin, plasminogen activator inhibitor type I, and von Willebrand factor (vWF)]. We also measured insulin, glucose, fibrinogen, total and HDL cholesterol, and the urinary albumin excretion (UAE), which may also be related to atherosclerosis. Results of these assays were related to the echographic assessment of the maximum intima-media thickness (IMTmax) at the carotid bifurcation, as an index of atherosclerosis in the carotids. PVD patients had a clearly elevated IMTmax [2.7 (1.1-3.1) mm, median (range)] compared with both UH patients [1.2 (0.8-2.4) mm] and controls [1 (0.6-2) mm]. sVCAM-1 was clearly higher in PVD patients [990 (273-1808) ng/mL, median (range)] versus 340 (236-975) ng/mL in UH and 386 (204-835) ng/mL in controls, and it separated clinical categories better than sICAM-1, vWF, glucose, insulin, UAE, triglycerides, or total, LDL or HDL cholesterol, sVCAM-1 was also the best biohumoral correlate of IMTmax (R = .59; P < .001) in univariate analysis. Because many of the biohumoral variables assessed were mutually intercorrelated, they were entered in a multivariate analysis to assess their contribution in explaining IMTmax variability. sVCAM-1 remained the only independent predictor of IMTmax and totally abolished the contribution of other variables to IMTmax variability. Thus, sVCAM-1 is a good biohumoral correlate of overt atherosclerosis, independent of underlying hypertension, and may be an in vivo marker of endothelial activation. Its potential value as a surrogate for global risk assessment and its behavior in intervention studies remain to be determined.

UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior.

The end-to-end association of chromosomes through their telomeres has been observed in normal cells of certain organisms, as well as in senescent and tumor cells. The molecular mechanisms underlying this phenomenon are currently unknown. We show here that five independent mutant alleles in the Drosophila UbcD1 gene cause frequent telomere-telomere attachments during both mitosis and male meiosis that are not seen in wild type. These telomeric associations involve all the telomeres of the D. melanogaster chromosome complement, albeit with different frequencies. The pattern of telomeric associations observed in UbcD1 mutants suggests strongly that the interphase chromosomes of wild-type larval brain cells maintain a Rab1 orientation within the nucleus, with the telomeres and centromeres segregated to opposite sides of the nucleus. The UbcD1 gene encodes a class I ubiquitin-conjugating (E2) enzyme. This indicates that ubiquitin-mediated proteolysis is normally needed to ensure proper telomere behavior during Drosophila cell division. We therefore suggest that at least one of the targets of UbcD1 ubiquitination is a telomere-associated polypeptide that may help maintain proper chromosomal orientation during interphase.

Urinary albumin excretion and atherosclerosis in essential hypertension.

1. Increased urinary albumin excretion is common in patients with essential hypertension and is at least to some extent correlated with prevailing blood pressure levels. However, the generalized vascular dysfunction present in advanced atherosclerotic disease may independently influence this parameter. 2. To evaluate this possibility, we assessed blood pressure, ultrasonographic carotid thickness, cardiac mass, minimum forearm vascular resistances, metabolic parameters and the angiotensin-converting enzyme genotype in patients with untreated essential hypertension and atherosclerotic peripheral vascular disease (n = 11). The results were compared with similar data obtained in matched groups of patients with uncomplicated hypertension and with normotensive control subjects (n = 11 per group). 3. Urinary albumin excretion was higher in hypertensive patients with atherosclerosis than in those without complications; carotid thickness was higher in atherosclerotic patients and a positive, statistically significant correlation existed between this parameter and urinary albumin excretion. In the same patient group, systolic blood pressure, fasting insulin and triacylglycerol levels were elevated and correlated with urinary albumin levels. However, differences in urinary albumin excretion persisted after taking into account the influence of those parameters by analysis of covariance. The distribution of angiotensin-converting enzyme genotype patterns and values of cardiac mass and minimum forearm vascular resistances did not differ significantly among the experimental groups. 4. The data suggest that vascular status may influence urinary albumin excretion in patients with essential hypertension, while confirming the importance of systolic blood pressure levels as a determinant of the raised urinary albumin excretion.

Peripheral ischemic occlusive arterial disease: comparison of color Doppler sonography and angiography.

We examined 334 legs in 167 consecutive patients with advanced peripheral ischemic disease using color Doppler sonography and angiography. Angiography revealed 714 lesions (369 nonsignificant stenoses, 297 significant stenoses, and 48 occlusions) in the 334 legs examined. Overall, color Doppler sonography revealed diagnostic agreement with angiography in 668 of 714 lesions (93.5%), including 343 of 369 (92.9%) nonsignificant stenoses, 279 of 297 (93.9%) significant stenoses, and 46 of 48 (95.8%) occlusions. Overestimation occurred in 26 of 369 (7%) nonsignificant stenoses and 3 of 297 (1%) significant stenoses. Underestimation was observed in 15 of 297 (5%) significant stenoses and in 2 of 48 (4.2%) occlusions. Peak systolic velocity ratio correlated better (P < 0.01) than peak systolic velocity with diameter reduction percentage as assessed at angiography. Color Doppler sonography is an accurate noninvasive method for evaluating patients with peripheral ischemic disease.

Relationship between carotid wall thickness and forearm blood flow reserve in hypertension.

BACKGROUND: The development of a reduced forearm blood flow reserve and an increased carotid intima media thickness is a well known consequence of the structural adaptation of arterioles and large arteries in response to hypertension. It is unknown, however, how those two processes relate to each other in the individual hypertensive patient. METHODS: Minimal forearm vascular resistances (Rmin, the ratio of mean blood pressure to postischemic plethysmographic peak forearm blood flow), common carotid intima media thickness (IMT, high-resolution ultrasonography), blood pressure (indirect method), left ventricular mass, posterior wall and septum thickness (by echocardiography) and lipids were measured in 15 men with mild-to-moderate essential hypertension without evidence of atherosclerotic involvement of the carotid arteries, and in 14 normotensive controls with a similar age range. RESULTS: Rmin and IMT were greater in hypertensives, and a statistically significant positive correlation existed between the two variables. Both Rmin and IMT correlated with left ventricular structure indices and blood pressure. Age showed a positive correlation with IMT, while lipids were unrelated to either parameter. CONCLUSIONS: The micro- and macrovascular segments of the hypertensive circulation readapt in parallel in response to elevated blood pressure, possibly through the commensurate development of medial hypertrophy.

[Imaging diagnosis in pseudomembranous colitis]. / La diagnostica per immagini nella colite pseudomembranosa.

Pseudomembranous colitis (PC) is a dangerous inflammatory disease which arises as a complication of systemic antibiotic therapy. The colon is the preferred localization of PC, which is caused by the alteration in the bacterial population of the bowel which favors the growth and activation of several germ types--e.g., the Clostridium difficile, whose toxins can damage the colonic mucosa deeply. Later, the condition may affect extramucosal structures thus causing an actual parietal alteration. Clinically, PC patients present with diarrhea, abdominal pain, onset or worsening of fever, impairement of the main body functions. The colonic mucosa appears macroscopically edematous and is covered with yellowish plaques, called "pseudomembranes", which adhere strictly to the mucosa. Pseudomembranes are made by fibrin, mucus, leucocytes and epithelial remnants. The diagnosis is made on the basis of laboratory tests--i.e. the demonstration of Clostridium difficile or its toxins in the feces. Endoscopy is the examination of choice when PC is suspected because it can demonstrate the typical mucosal alterations directly. In this paper the main etiologic, pathologic and clinical features of PC are presented and the role of diagnostic imaging examinations is discussed, not only in demonstrating the typical lesions but also in the spatial evaluation of the condition and in its follow-up.

Soluble interleukin-2 receptor levels in lupus nephritis.

Soluble interleukin-2 receptor (IL-2R) levels were measured and correlated prospectively with clinical, histologic and serologic findings over a 9-month period in 62 lupus patients. Initially, 39 patients had clinical nephritis and 23 patients did not have nephritis. The 62 lupus patients has significantly higher IL-2R than 15 normal controls, most of this difference attributable to patients with nephritis. During lupus nephritis flare 9 of 10 patients showed significant elevations of IL-2R while only 6 of the 10 patients showed either elevation of anti-DNA antibody or decrease in CH50. During disease remission or stable clinical activity changes in IL-2R levels paralleled changes in anti-DNA antibody and CH50. Nephritis patients with cellular proliferative histology had significantly higher IL-2R levels than those with membranous or mesangial nephropathy. IL-2R correlated strongly with histologic activity and chronicity indices, IgG and C3 deposition whereas anti-DNA antibody and CH50 levels did not. IL-2R levels did not correlate with serum creatinine suggesting that elevations of IL-2R were not simply due to decreased clearance. These observations suggest that serum IL-2R level is a useful marker of disease activity in lupus nephritis and may serve as a helpful adjunct in management of this disorder.

Misdiagnosis of rheumatoid arthritis in an elderly woman with gout.

Polyarticular gout may be misdiagnosed in the elderly. This reflects the confusing clinical presentation of "diuretic gout" in the elderly, characterized by polyarticular onset, subacute symptoms, hand involvement, and early development of tophi. A misdiagnosis of rheumatoid arthritis can lead to poor treatment of gout, failure to recognize underlying renal insufficiency, and associated cardiac risks. Hyperuricemia may reflect systemic ATP depletion in acutely ill patients and thus represents a predictor for mortality. Medical treatment of polyarticular gout in elderly patients with compromised cardiac and renal function requires recognition of the clinical profile and consideration of the increased toxicity from standard therapies.

Cognitive function in patients with symptomatic dilated cardiomyopathy before and after cardiac transplantation.

Pre- and postoperative cognitive performance of candidates for heart transplantation was examined by means of an extensive battery of neuropsychological measures. A total of 54 patients completed the preoperative cognitive protocol, 20 of whom also completed postoperative testing. Age (less than 50 or greater than or equal to 50 years of age) and the primary cause of cardiac deterioration (idiopathic, ischemic disease or rheumatic/congenital defects) were the major classification variables. The main findings of this study were: 1) Preoperative neuropsychological measures revealed a high frequency of impaired performance, particularly in measures of memory, higher level processing of information and motor speed. A pattern consistent with diffuse rather than focal or lateralized cerebral deficits was observed. Significant differences were not found on the basis of the cause of cardiac disease, but some were observed for age (the older group was more impaired). 2) A comparison of pre- and postoperative cognitive scores failed to show significant cognitive improvement despite greatly improved physical health. The cause of cardiac deterioration was not differentially associated with postoperative cognitive performance, and there was equivocal evidence for age effects. These findings may have implications for the selection of transplant recipients and the timing of transplantation surgery.