Normalized regional brain atrophy measurements in multiple sclerosis

There is still a controversy regarding the best regional brain atrophy measurements in multiple sclerosis (MS) studies. The aim of this study was to establish whether, in a cross-sectional study, the normalized measurements of regional brain atrophy correlate better with the MRI-defined regional brain lesions than the absolute measurements of regional brain atrophy. We assessed 45 patients with clinically definite relapsing–remitting (RR) MS (median disease duration 12 years), and measured T1-lesion load (LL) and T2-LL of frontal lobes and pons, using a reproducible semi-automated technique. The regional brain parenchymal volume (RBPV) of frontal lobes and pons was obtained by use of a computerized interactive program, which incorporates semi-automated and automated segmentation processes. A normalized measurement, the regional brain parenchymal fraction (RBPF), was calculated as the ratio of RBPV to the total volume of the parenchyma and the cerebrospinal fluid (CSF) in the frontal lobes and in the region of the pons. The total regional brain volume fraction (TRBVF) was obtained after we had corrected for the total volume of the parenchyma and the CSF in the frontal lobes and in the region of the pons for the total intracranial volume. The mean coefficient of variation (CV) for RBPF of the pons was 1% for intra-observer reproducibility and 1.4% for inter-observer reproducibility. Generally, the normalized measurements of regional brain atrophy correlated with regional brain volumes and disability better than did the absolute measurements. RBPF and TRBVF correlated with T2-LL of the pons (r=–0.37, P=0.011, and r= –0.40, P=0.0005 respectively) and with T1-LL of the pons (r=–0.27, P=0.046, and r=–0.31, P=0.04, respectively), whereas RBPV did not (r=–0.18, P = NS). T1-LL of the frontal lobes was related to RBPF (r=–0.32, P=0.033) and TRBVF (r=–0.29, P=0.05), but not to RBPV (R=–0.27, P= NS). There was only a trend of correlation between T2-LL of the frontal lobes and RBPF (r=–0.27, P=0.06) and TRBVF (r=–0.28, P=0.057), and no correlation with RBPV (r=–0.23, P= NS). The magnitude of correlation between the expanded disability status scale (EDSS) and pontine and frontal lobe RBPF and TRBVF was more than twice as high as the correlation between EDSS and RBPV of the same regions. These data suggest that normalized regional brain atrophy measurements are preferable to absolute regional measurements in cross-sectional studies.     

Adenocarcinoma of the third and fourth portions of the duodenum: results of surgical treatment

HYPOTHESIS: To verify the adequacy of duodenal segmentectomy after intestinal derotation in the treatment of primary adenocarcinoma of the third and fourth portions of the duodenum. DESIGN: A retrospective review of the surgical management of patients who underwent derotation of the third and fourth portions of the duodenum was undertaken to determine long-term outcome. SETTING: Departments of surgery in 3 university hospitals. PATIENTS: Between January 1, 1980, and December 31, 2000, 47 patients with primary adenocarcinoma of the third and fourth portions of the duodenum were surgically treated at 3 different institutions. MAIN OUTCOME MEASURES: Details of primary surgery were abstracted from clinical records of the original hospital referral. Postoperative clinical course and long-term outcome were evaluated by a review of the hospital records and follow-up. RESULTS: The results of a barium swallow test series was positive in 38 cases (80.8%) and esophagogastroduodenoscopy was primarily diagnostic in 30 patients (63.8%). In all cases duodenal segmentectomy was attempted. Twenty-two patients underwent palliative gastrojejunal bypass and in 9 patients pancreaticoduodenectomy was performed. In 16 cases duodenal segmentectomy was performed after intestinal derotation. Anastomoses were performed manually in all cases. Fifteen of the resected patients died of recurrent disease. A median (SD) disease-free survival of 36 (23.6) months (range, 6-85 months) was observed. The median (SD) overall survival was 37.5 (23.9) months (range, 11-85 months), the overall 5-year survival rate was 23% (11 patients), and the actuarial 5-year survival rate was 51% (24 patients). CONCLUSIONS: Duodenal segmentectomy associated with intestinal derotation was shown to be a straightforward, safe procedure for the treatment of the primary adenocarcinoma of the third and fourth portions of the duodenum. This surgical procedure should be preferred to pancreaticoduodenectomy because it is associated with negligible rates of morbidity and mortality, while allowing for satisfactory margin clearance and adequate lymphadenectomy.     

Myocardial lactate metabolism in relation to preoperative regional wall motion and to early functional recovery after coronary revascularization

OBJECTIVE: To evaluate myocardial lactate metabolism as a marker of functional status after surgical coronary revascularization. DESIGN: Single-center, prospective, cohort study. SETTING: Tertiary care teaching hospital. PARTICIPANTS: Fifty patients with stable angina, ejection fraction >0.40, undergoing coronary artery bypass surgery for multiple-vessel disease. MEASUREMENTS AND MAIN RESULTS: Before (T1) and 30 minutes (T2) after coronary artery bypass grafting, the authors simultaneously sampled blood from artery and coronary sinus to determine myocardial lactate dynamics and performed transesophageal echocardiography (TEE) to assess segmental wall motion. Wall motion score index (WMSI) was calculated with an online/offline comparison. At T2, WMSI improved from 1.40 +/- 0.31 to 1.17 +/- 0.23 (p = 0.0001). Preoperatively, 2 patterns of lactate balance were found: 39 patients were lactate extractors (17% +/- 10%) and 11 were lactate producers (-11% +/- 11%). At T2, lactate metabolism was shifted towards a pattern opposite to the baseline: delta lactate extraction was -8% +/- 16% in extractors at T1 versus 7% +/- 9% in producers at T1 (p = 0.003). Changes in WMSI were not correlated with changes in lactate utilization. No single preoperative variable predicted postoperative WMSI or its changes from baseline. Cardiopulmonary bypass (CPB) time was the only significant predictor of postoperative lactate extraction by multivariate regression (r = -0.46, p = 0.001): at T2, patients in the highest CPB time quartile showed frank lactate production (-6% +/- 13%) when compared with those in the lowest quartile (15% +/- 11%, p = 0.005). However, postoperative WMSI was similar in different CPB time groups. CONCLUSIONS: Myocardial lactate metabolism pattern is not associated with functional status before and early after successful coronary revascularization. CPB time was the only significant predictor of postoperative lactate extraction. Measurement of lactate does not appear to be a valuable tool to assess the coupling of myocardial regional function and metabolism in the setting of coronary artery surgery and mild-to-moderate functional impairment.     

Resolution of the oedema associated with allergic pulmonary inflammation in rats assessed noninvasively by magnetic resonance imaging

1. Magnetic resonance imaging (MRI) was used to study noninvasively the effects of compounds to resolve inflammation induced by ovalbumin (OVA) challenge in the lungs of actively sensitised rats. 2. Marked oedematous signals were detected between 24 and 96 h following OVA in vehicle-treated animals. When administered 24 h after OVA, budesonide, a glucocorticosteroid, or 4-(8-benzo[1,2,5]oxadiazol-5-yl-[1,7]naphthyridin-6-yl)-benzoic acid (NVP-ABE171), a selective phosphodiesterase 4 inhibitor, increased the rate of resolution of established oedematous signals detected by MRI. The effect was evident 3 h after drug administration and the signals were nearly fully resolved at 96 h postchallenge. 3. The drug-induced rapid resolution of MRI signals was not accompanied by changes in parameters of inflammation in the bronchoalveolar lavage fluid, but was associated with perivascular oedema detected histologically. 4. In conclusion, the effects of anti-inflammatory drugs on a component of allergic inflammation can be monitored by following with MRI the rate of resolution of the associated oedematous signals.     

Octreotide in the treatment of lymphorrhea after renal transplantation: a preliminary experience

BACKGROUND: Lymphorrhea is a minor complication after kidney transplantation but may develop into a lymphocele and prolong hospital stay. Treatment is conservative based on percutaneous drainage until lymphatic leakage cessation. It has been reported that octreotide has beneficial effects to treat lymphorrhea after axillary node dissection and excision of lymphatic malformations. The aim of this study was to report preliminary experience about octreotide treatment in lymphorrea after kidney transplantation. MATERIALS AND METHODS: This retrospective study included 20 recipients of cadaveric kidney allografts with posttransplant lymphorrhea including 10 treated with instillation of povidone iodate solution, and the other 10 with octreotide (0.1 mg three times a day subcutaneously). We reviewed the daily amount of fluid collection, duration of lymphorrhea, complications, lymphocele formation, rejection episodes, graft outcomes, and hospital stay. RESULTS: The average duration of lymphorrhea was 8.5 (+/-4.5) and 16.3 (+/-7.3) days for the octreotide versus the povidone groups, respectively (P = .001). No complications occurred among the octreotide group, while three lymphoceles grew among patients treated with povidone solution. No differences were observed for acute rejection episodes or renal function between the groups. No octreotide-related adverse events were noted. CONCLUSION: The mean length of lymphorrhea was lower with octreotide versus iodate povidone solution treatment. There was a shorter hospital stay and minor patient discomfort. In conclusion, lymphatic leakage after kidney transplantation may be successfully managed by octreotide administration.     

Intestinal and systemic endotoxaemia after laparotomic or laparoscopic cholecystectomy

Since laparoscopic cholecystectomy (LC) is widely recognised as being a "mild" or minimally invasive kind surgery, the aim of this prospective non-randomised study was to investigate the effect of intestinal manipulation on intestinal permeability and endotoxaemia in patients undergoing elective cholecystectomy, comparing the laparoscopic and laparotomic approaches. The intestine is susceptible to operations at remote locations, and the barrier function is altered during intestinal manipulation, leading to bacterial or endotoxin translocation into the systemic circulation. Fifty-three patients undergoing elective cholecystectomy were divided into two groups on the basis of laparotomic (n = 27) or laparoscopic (n = 26) approach. Intestinal permeability was measured preoperatively, and on day 1 and day 3 after surgery using the lactulose/mannitol absorption test. Serial venous samples were taken at 0, 30, 60, 90, 120 and 180 minutes, and at 12, 24 and 48 hours after surgery, for endotoxin measurement using the chromogenic limulus amoebocyte lysate assay. Intestinal permeability was significantly increased on day 1 [0.106 +/- 0.0005 (mean +/- S.E.M.)] in the laparotomic group compared to the preoperative level (0.019 +/- 0.005, p < 0.05) and to the laparoscopic group on day 1 (0.019 +/- 0.005, p < 0.05) which showed no change in comparison with the preoperative level. A significantly higher concentration of systemic endotoxin was detected intraoperatively in the laparotomic group of patients in comparison with the laparoscopic group (p < 0.05). There was significant positive correlation between systemic endotoxaemia and intestinal permeability (rs = 0.958; p = 0.001). An increase in intestinal permeability and degree of systemic endotoxaemia are observed during laparotomic cholecystectomy. This suggets that intestinal manipulation may impair the mucosal barrier function of the gut and contribute to the systemic inflammatory response seen in open cholecystectomy.     

Girls growing through adolescence have a higher risk of poor health

Introduction:

Self rated health, in adult population, is strongly associated with mortality and life expectancy. In younger people this association is less evident, but it may anticipate a similar risk in adult life. Our research, based on the HBSC (Health Behaviour in School-Aged Children) International collaboration, contributes to deepen the knowledge in this field by monitoring adolescents’ health through a multi-national survey involving 29 European countries, plus North America (Canada and USA) and Israel.

Methods:

Following an established methodology, the HBSC survey has elaborated a questionnaire on health and health behaviour, filled in by a representative national sample of 11-, 13- and 15-year-old boys and girls. The sample is constituted of more than 160,000 subjects interviewed during the 2001/2002 survey. Reported symptoms and self-rated health have been analysed by sex and age and through the different countries.

Results:

Girls resulted to have a poorer perception of their health, with respect to males, at all ages and in all countries (Overall OR = 1.70, 95% CI: 1.66–1.76). Age increases this risk both for males and females, with an average increase of 32% (95% CI: 29–34%) per year in the age-range 11–15. The situation is similar for reported symptoms, with an overall OR of 1.81 (95% CI: 1.77–1.85) for females of reporting three or more symptoms at least once a week; also this risk increases of 26% (95% CI: 24–27%) per year during the pre-adolescence phase. In both cases it could be shown a significant interaction effect between age and gender: OR = 1.19 (CI: 1.15–1.23) for perceived health and OR = 1.26 (CI: 1.23–1.29) for reported symptoms in females with respect to males.

Conclusions:

Even if adolescence is described as the healthiest period of life, a consistent minority of young people perceive and report a poor health and a high number of symptoms. Females are constantly in a worse position than males and older age groups are worse than younger ones.     

Enhanced nasal absorption of hydrophilic markers after dosing with AT1002, a tight junction modulator

AT1002 is a six-mer synthetic peptide, H-FCIGRL-OH, that retains the delta G and Zot biological activity of reversibly opening tight junctions and increases the paracellular transport of drugs. The objective of this study was to evaluate the possible use of AT1002 in enhancing the nasal availability of macromolecules using large paracellular markers as model agents. Male Sprague–Dawley rats cannulated in the jugular vein were randomly assigned to receive radiolabelled paracellular markers, [¹⁴C]PEG4000 or [¹⁴C]inulin, with/without AT1002, for each intranasal study. The plasma concentration of PEG4000 with AT1002 (10 mg/kg) was significantly higher than that from PEG4000 control over 360 min following intranasal administration. The AUC_0–360 min and C_max from the PEG4000/AT1002 (10 mg/kg) treatment were statistically (p < 0.05) increased to 235% and 357%, of control, respectively. When inulin was administered with AT1002 (10 mg/kg), the plasma concentration was significantly higher (p < 0.05) than control over 360 min, and increases (p < 0.05) of 292% and 315% for AUC_0–360 min and C_max over control were observed, respectively. AT1002 significantly increased the nasal absorption of molecular weight markers, PEG4000 and inulin. This study suggests that AT1002 may be used to enhance the systemic availability of macromolecules when administered concurrently.