Dosimetric effect of variable rectum and sigmoid colon filling during carbon ion radiotherapy to sacral chordoma.

PURPOSE: Carbon ion radiotherapy (CIRT) is sensitive to anatomical density variations. We examined the dosimetric effect of variable intestinal filling condition during CIRT to ten sacral chordoma patients. METHODS: For each patient, eight virtual computed tomography scans (vCTs) were generated by varying the density distribution within the rectum and the sigmoid in the planning computed tomography (pCT) with a density override approach mimicking a heterogeneous combination of gas and feces. Totally full and empty intestinal preparations were modelled. In addition, five different intestinal filling conditions were modelled by a mixed density pattern derived from two combined and weighted Gaussian distributions simulating gas and feces respectively. Finally, a patient-specific mixing proportion was estimated by evaluating the daily amount of gas detected in the cone beam computed tomography (CBCT). Dose distribution was recalculated on each vCT and dose volume histograms (DVHs) were examined. RESULTS: No target coverage degradation was observed at different vCTs. Rectum and sigma dose degradation ranged respectively between: [-6.7; 21.6]GyE and [-0.7; 15.4]GyE for D50%; [-377.4; 1197.9] and [-95.2; 1027.5] for AUC; [-1.2; 10.7]GyE and [-2.6; 21.5]GyE for D1%. CONCLUSIONS: Variation of intestinal density can greatly influence the penetration depth of charged particle and might compromise dose distribution. In particular cases, with large clinical target volume in very close proximity to rectum and sigmoid colon, it is appropriate to evaluate the amount of gas present in the daily CBCT images even if it is totally included in the reference planning structures.

Exercise-induced T-wave normalization predicts recovery of regional contractile function after anterior myocardial infarction.

AIMS: We investigated the ability of T-wave pseudonormalization and ST-segment elevation, which are demonstrated in infarct-related leads during submaximal exercise testing, to predict late recovery of contractile function. METHODS: We studied 88 consecutive patients (73 males, mean age 59 +/- 8 years) with anterior infarction, persistent T-wave inversion and a documented lesion of the proximal segment of the left anterior descending coronary artery. They all underwent 2D-echocardiography on admission, 4 weeks as well as 6 months after myocardial infarction to evaluate the dysfunction score and the ejection fraction. Submaximal (75% of maximal predicted heart rate) exercise testing was performed in 80 patients 2 weeks after myocardial infarction following discontinuation of treatment. RESULTS: During exercise testing, 59 of the 88 patients showing negative T-waves on the resting electrocardiogram exhibited pseudonormalization (group A) in at least three adjacent precordial leads, whilst 29 (group B) did not. Patients of group A more frequently exhibited an early creatine kinase peak (41% vs 24%, P < 0.05) and residual angiographic perfusion (97% vs 69%, P < 0.05). The dysfunction score did not change in group B (from 19 +/- 7 to 22 +/- 4), but decreased in group A (from 18 +/- 4 to 11 +/- 6 P < 0.05). The ejection fraction was similar in the two groups on admission (group A: 48 +/- 7%, group B: 45 +/- 10%), but was significantly different at 4-week (52 +/- 99 vs 42 +/- 11%, P < 0.05) and 6-month follow-up (58 +/- 9 vs 44 +/- 10%, P < 0.01). The concomitant presence of ST-segment elevation and T-wave normalization showed the highest positive predictive value for left ventricular function recovery (100%). CONCLUSIONS: T-wave normalization induced by submaximal exercise test is frequently associated with residual perfusion to the infarct area and predicts progressive improvement in regional wall motion, especially if associated with ST-segment elevation. Therefore, these electrocardiographic findings may be used as easily obtainable markers of residual viability that predict late recovery in contractile function.

[Family burden in schizophrenia: effects of socio-environmental and clinical variables and family intervention]. / Carico familiare nella schizofrenia: effetto delle variabili cliniche e socio-ambientali e degli interventi familiari.

OBJECTIVE: Description of burden, attitudes and received professional support in a sample of relatives of patients with schizophrenia recruited in 8 Italian Mental Health Services (MHS), stratified by geographic areas and population density. DESIGN: Cross-sectional study on key-relatives of clinically stable patients with a DSM-IV diagnosis of schizophrenia. Evaluation of: a) relationships of family burden with patient's clinical characteristics, family's socio-demographic variables, relative's attitudes toward the patient, professional and social support received by the family; b) differences in the levels of burden, attitudes and support received by the family with respect to geographical area and population density. SETTING: 8 Italian MHS stratified by geographic areas (Northern, Central, Southern Italy) and population density (urban vs. rural areas). MAIN OUTCOME MEASURES: Patient's clinical status and social functioning: BPRS and ADC. Family burden, attitudes and support received by the family: FPQ. RESULTS: Data on 144 patients and their key-relatives were collected. Higher levels of burden were found among relatives referring to Southern MHS. The burden was found positively correlated with the levels of patients' BPRS positive and manic/hostility symptoms and disability, and with the number of daily hours spent by the relative in contact with the patient, and negatively correlated with the levels of professional support received by the family. CONCLUSIONS: The results of this study highlight the need to provide rehabilitative programmes for patients with schizophrenia as well as informative and psychoeducational interventions for their families.

Soluble E-selectin and intercellular adhesion molecule-1 plasma levels increase during acute myocardial infarction.

Previous studies have shown that adhesion molecules play a crucial role in leukocyte-endothelium interactions that occur during myocardial ischemia and reperfusion. We assessed the plasma levels of the soluble form of E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) in 15 patients with acute myocardial infarction (AMI) and in 15 controls with chronic stable angina. In patients with AMI, the levels of sE-selectin and sICAM-1 increased significantly during the first 8 h after infarction and subsequently decreased. Soluble E-selectin levels were inversely related to the peak plasma levels of creatine kinase-MB (CK-MB), and the time course of their appearance in plasma correlated with that of neutrophil count and plasma D-dimer. In individual patients, peak and mean sICAM-1 levels correlated respectively with plasma D-dimer concentrations and monocyte count, but no correlation were found when their time courses were analyzed. Eight hours after symptom onset, the mean plasma sE-selectin levels were higher in patients with AMI than in those with stable angina, whereas no significant differences were found in mean plasma sICAM-1 levels between the two groups at every time analyzed. In the acute phase of MI (a) sE-selectin and sICAM-1 levels increase during the first 8 h and subsequently decrease; (b) the increase in sE-selectin probably reflects activation of endothelial cells, correlates with other inflammatory and coagulation parameters, and is inversely related to the degree of myocardial damage; and (c) sICAM-1 plasma levels do not represent a good marker of "cell activation" because they reflect activation of different cells and may be affected by different conditions.

Coronary recanalization by elective angioplasty prevents ventricular dilation after anterior myocardial infarction.

OBJECTIVES: In a prospective study we evaluated whether late recanalization of the left anterior descending coronary artery (LAD) affects ventricular volume and function after anterior myocardial infarction. BACKGROUND: Persistent coronary occlusion after anterior myocardial infarction leads to ventricular dilation and heart failure. METHODS: We studied 73 consecutive patients with acute anterior myocardial infarction as a first cardiac event; all had an isolated lesion or occlusion of the proximal LAD. Six patients died before hospital discharge. The 67 survivors were classified into two groups: group I (patent LAD and good distal flow, n = 40) and group II (LAD occlusion or subocclusion, n = 27). The 20 patients in group I who had significant residual stenosis and all patients in group II underwent elective percutaneous transluminal coronary angioplasty (PTCA) within 18 days of myocardial infarction. The procedure was successful in 17 patients in group I (group IB) and in 16 patients in group II (group IIA): in the remaining 11 patients of group II, patency could not be reestablished (group IIB). Left ventricular volumes, ejection fraction and a dysfunction score were measured by echocardiography on admission, before PTCA, at discharge and after 3 and 6 months. RESULTS: Although cumulative ST segment elevation was similar in groups I and II, ejection fraction and dysfunction score were significantly worse in group II. However, ventricular function and volumes progressively improved in group IIA, whereas group IIB exhibited progressive deterioration of function (dysfunction score [mean +/- SD] increased from 21 +/- 6 to 25 +/- 8, p < 0.05; ejection fraction decreased from 43 +/- 10% to 37 +/- 11%, p < 0.05); and end-systolic volume increased from 34 +/- 10 to 72 +/- 28 ml/m2, p < 0.05). Patients in group IIB also had worse effort tolerance, higher heart rate at rest, lower blood pressure and significantly greater prevalence of chronic heart failure. CONCLUSIONS: Delayed PTCA of an occluded LAD can frequently restore vessel patency. Success appears to be associated with better ventricular function and a lack of chronic dilation. Large randomized studies are warranted to evaluate the effect of delayed PTCA on late mortality.

Thrombolytic therapy reduces the incidence of left ventricular thrombus after anterior myocardial infarction. Relationship to vessel patency and infarct size.

BACKGROUND: Controversial evidence exists as to whether thrombolytic therapy reduces the incidence of left ventricular thrombus in acute myocardial infarction and, if so, how this relates to successful reperfusion. METHODS: Four hundred and eighteen consecutive patients underwent echocardiography and coronary angiography within 3 weeks of an acute myocardial infarction. A dyssynergic score was calculated by analysing regional wall motion in 18 left ventricular segments. The infarct-related artery was considered patent if TIMI grade 2 or 3 flow and less than 90% stenosis were present. Retrograde perfusion by Rentrop's grade 2 or 3 collaterals was considered significant. RESULTS: Large anterior myocardial infarctions were associated with the highest prevalence (39%) of left ventricular thrombosis. Thrombus was also very frequent if the left anterior descending coronary artery was occluded and no collaterals to the infarct area were seen (75%). Anticoagulant therapy reduced the prevalence of left ventricular thrombus, regardless of whether the infarct-related vessel was patent or not. Conversely, in patients undergoing thrombolysis the incidence of left ventricular thrombosis was lower when the left anterior descending coronary artery was patent, and especially when an early creatine kinase peak, suggestive of reperfusion, was recorded (7%). Finally, the presence of left ventricular thrombosis was inversely related to the asynergy score. CONCLUSION: These observations suggest that the presence of left ventricular thrombus is related to the extent of myocardial damage. Thrombolytic therapy reduces thrombus probably by salvaging myocardium at risk.

[A false diagnosis of hypertrophic myocardiopathy in pheochromocytoma]. / Falso diagnóstico de miocardiopatia hipertrófica em feocromocitoma.

A 24 year-old man was admitted with hypertensive crises and diagnosis hypothesis of neurofibromathosis and pheochromocytoma with blood pressure of 150 x 110mmHg and in use of anti-hypertensive drugs. The electrocardiogram (EKG) showed left ventricle hypertrophy. An echocardiogram showed interventricular septum (IVS) thickness of 16mm, posterior wall (PW) thickness of 11mm (ratio IVS/PW was 1.4). Diastolic ventricular diameter was 39mm with gradient of 52mmHg and mild mitral-valve murmur by pulsate Doppler. Increased vanillylmandelic acid and metanephrines in a 24-hour sample of urine has confirmed diagnosis of pheochromocytoma within was localized by 131I metaiodobenzyl-guanidine scan and computerized axial tomography. The patient was submitted to right adrenalectomy. Blood pressure was normalized. Evaluation an year later revealed a healthy man with normal laboratory exams, EKG and echocardiogram. It seems that the hypertrophy was consequence of the hypertension and pheochromocytoma, was not hypertrophic cardiomyopathy.

[Lipoprotein (a), apolipoproteins and the lipid profile late after heart transplantation]. / Lipoproteína (a), apolipoproteínas e perfil lipídico em fase tardia após o transplante cardíaco.

PURPOSE--To evaluate if the levels of lipoprotein (a) [Lp(a)], apolipoproteins (apo) A1, B and the lipid profile (LP) differ among heart transplantation (HT) patients, with coronary artery disease (CAD) and patients without CAD (NL) and if LP discriminates patients with graft vascular disease (GVD). METHODS--A hundred and seventy patients separated in 3 groups: I) HT [n = 43 46 +/- 15 years, 24 months (median) after transplantation], of these 28 were submitted to serial angiography after the first year of transplantation subgroups with GVD (n = 9) and without GVD (NGVD) (n = 19); II) CAD (n = 72, 48 +/- 6 years); III) NL (n = 45, 50 +/- 6 years). RESULTS--HT presented higher apo A1 levels than CAD and NL (1.5 +/- 0.5 vs 1.2 +/- 0.05 vs 1.1 +/- 0.06 g/l p < 0.05 respectively). Apo B was higher on CAD than in HT and NL (1.5 +/- 0.05 vs 1.2 +/- 0.07 vs 1.3 +/- 0.09 g/l p < 0.05). Lp (a) presented a trend to higher levels in HT and CAD than in NL [25(2-97), 24(1-130) and 15 (1-100) mg/dl, p = 0.05)]. However, when individually evaluated against NL Lp(a) levels were higher in HT and CAD (p = 0.019 and 0.03 respectively). LP did not differ between GVD and NGVD. CONCLUSION--Increased Lp(a) levels after transplantation might be related to the high prevalence of GVD. The LP did not discriminate GVD.

[An aneurysm of the interatrial septum and cerebral embolic events: a clinical case and review of the literature]. / Aneurisma del setto interatriale ed eventi embolici cerebrali: caso clinico e revisione della letteratura.

Previous reports have described an association between atrial septal aneurysm and cerebral embolic events. We report the case of 68-year-old woman who was referred for evaluation of two syncopal episodes that had occurred within the previous three months. Physical examination, 12-lead ECG and exercise stress test were unremarkable; a 24-hour Holter monitoring did not show cardiac arrhythmias, and carotid ultrasonography excluded atherosclerotic lesions. Magnetic resonance imaging of the brain revealed multiple areas of decreased tissue density. Two-dimensional transthoracic echocardiography showed an atrial septal aneurysm that was confirmed by transesophageal imaging, which improved its morphologic characterization and ruled out the possibility of other atrial abnormalities with embolic potential. In conclusion, the syncopal episodes observed in our patient were likely due to cerebral embolism. This observation confirms the relation between atrial septal aneurysm and cerebrovascular ischemic events. As previously indicated, the presence of this abnormality dictates the need for anticoagulant therapy.

One-hundred-and-six gamete intra-fallopian transfer procedures with donor semen.

A single attempt of gamete intra-Fallopian transfer was performed in 106 patients, who had previously failed to become pregnant after a certain number of artificial donor inseminations. A maximum of six unselected oocytes were transferred into the tubes. Fifty-five clinical pregnancies (51.9%) were obtained. There were 11 multiple pregnancies (20%) and 10 miscarriages (18.1%). Only one ectopic pregnancy occurred (1.8%). The age of the patients and the previous number of failed inseminations did not have any significant influence on the outcome of the procedure, whereas the number of transferred oocytes had a proportional, significant correlation with the pregnancy rate.

Non-surgical flushing of the uterus for pre-embryo recovery: possible clinical applications.

Growing interest in preimplantation genetic diagnosis has indicated uterine flushing as one method for obtaining human preimplantation embryos. To date, our institution has performed non-surgical uterine flushing to donate the recovered embryos to infertile recipients. We performed 127 flushings in 127 cycles using a modified urinary bladder catheter. Using the donors' natural cycles, a single ovum was recuperated in 37 out of 88 flushings. In 17 flushings, clomiphene citrate was given to the donors and 14 ova were found in nine positive recoveries. Human menopausal gonadotrophins were administered to the donors in 22 flushings and 22 ova were located in 14 positive recoveries. In total, 22 blastocysts, 11 morulae and 13 pre-embryos at the 2- to 16-cell stages were found. When transferred, these embryos gave rise to 18 clinical pregnancies in the recipients (40.9% of the transfers; 14.1% of the flushings). In comparison with natural cycles, superovulation of donors did not significantly increase the recipients' pregnancy rate. At present, non-surgical recovery of uterine pre-embryos does not seem to carry much potential as a tool for infertility treatment, or for genetic diagnosis. This is because currently available alternative methods are more successful.

Gamete intrafallopian transfer in a woman with tubal occlusion. A case report.

Gamete intrafallopian transfer (GIFT) is usually performed when at least one fallopian tube is normally patent. We used GIFT in a case of bilateral tubal occlusion. The patient, who had primary ovarian failure, was enrolled in our GIFT program since it was assumed that her tubes were normally patent. Unexpectedly, at laparoscopy both tubes turned out to be distally occluded; nevertheless, GIFT was carried out by piercing the tubal wall. At this writing the patient had reached the 11th week of a normal intrauterine gestation and was still undergoing hormone replacement therapy.

Oocyte donation by gamete intra-fallopian transfer to amenorrhoeic and cycling patients given replacement steroids.

Thirteen procedures of oocyte donation by the gamete intra-Fallopian transfer (GIFT) technique are described. The patients included six women with premature ovarian failure, four normally cycling women with unexplained infertility who responded poorly to super-ovulation induction in preparation for GIFT, and lastly one woman carrier of a 16/21 balanced translocation. Two patients had oocytes donated on two occasions. Oocyte donors were recruited either among the patients' relatives (n = 4), or among GIFT or IVF patients (n = 8), who altruistically donated their extra oocytes. Donors were superovulated and oocytes collected laparoscopically or vaginally under ultrasound guidance. Donors did not suffer any complications. Recipients were given exogenous estrogens, and exogenous progesterone was added from the day of donation. Seven clinical pregnancies were obtained (53.8% per attempt); one set of triplets aborted at 14 weeks. Donation took place on replacement day 12-18 and pregnancies were obtained in patients receiving oocytes throughout this temporal window. The increasing availability of embryo-freezing facilities will probably reduce the number of ova available for donation. Therefore, the patients' families may become a precious source of donated eggs, especially for those patients having large families, with strong family ties.

Surrogate human fallopian tubes for overcoming tubal infertility.

A procedure has been devised in order to establish a pregnancy in a patient with severe, untreatable tubal infertility who had unsuccessfully undergone tubal reconstructive surgery and repeated in-vitro fertilization procedures. This technique, which involves a volunteer, fertile woman, results from the combination of two infertility treatments: namely gamete intra-Fallopian transfer and uterine flushing. The gametes of the infertile couple were introduced into the distal tube of a synchronized volunteer woman; after 5 days, the embryos, recovered by lavage of the volunteer's uterus, were transferred into the patient's uterus with a resulting pregnancy and delivery.

Transfer of pre-embryos donated and fertilized in vivo to recipients given a steroid replacement therapy.

This study describes eleven procedures of non-surgical recovery of preimplantation conceptuses from the uteri of eight fertile donor women and the transfer of the recovered pre-embryos into the uteri of infertile recipients with primary ovarian failure, or with hypothalamic--pituitary failure. Conjugated oestrogens and progesterone were administered to recipients as replacement steroids during the first 20 weeks of pregnancy, in order to produce a secretory endometrium allowing nidation and development of the transferred conceptuses. Five pre-embryo transfers resulted in two viable pregnancies and one early abortion. Non-surgical pre-embryo transfer is a simple and practical method for providing donated ova to women lacking efficient ovarian function.