Human responses against HER-2-positive cancer cells in human immune system-engrafted mice.

BACKGROUND: Human immune system (HIS)-engrafted mice are new tools to investigate human immune responses. Here, we used HIS mice to study human immune responses against human HER-2-positive cancer cells and their ability to control tumour growth and metastasis. METHODS: BALB/c Rag2(-/-), Il2rg(-/-) mice were engrafted with CD34(+) or CD133(+) human cord blood hematopoietic stem cells (HSC) and vaccinated with human HER-2-positive cancer cells SK-OV-3 combined to human IL-12. RESULTS: Both CD34(+) or CD133(+) human HSC gave long-term engraftment and differentiation, both in peripheral blood and in lymphoid organs, and production of human antibodies. Vaccinated mice produced specific anti-HER-2 human IgG. An s.c. SK-OV-3 challenge was significantly inhibited (but not abolished) in both vaccinated and non-vaccinated HIS mice. Tumours were heavily infiltrated with human and murine cells, mice showed NK cells and production of human interferon-γ, that could contribute to tumour growth inhibition. Vaccinated HIS mice showed significantly inhibited lung metastases when compared with non-vaccinated HIS mice and to non-HIS mice, along with higher levels of tumour-infiltrating human dendritic cells. CONCLUSION: Anti-HER-2 responses were elicited through an adjuvanted allogeneic cancer cell vaccine in HIS mice. Human immune responses elicited in HIS mice effectively inhibited lung metastases.

Characterization of a 2D ion chamber array for the verification of radiotherapy treatments.

In this study we investigated the characteristics of a commercial ion chamber array and its performance in the verification of radiotherapy plans. The device was the 2D Array Seven29 model (PTW, Freiburg, Germany). This is a two-dimensional detector array with 729 ionization chambers uniformly arranged in a 27 x 27 matrix with an active area of 27 x 27 cm(2). The detector short-, medium- and long-term reproducibility have been tested through an extensive set of repeated measurements. Short-term reproducibility was well within 0.2%. Medium- and long-term reproducibility were within 1%, including set-up reproducibility errors and linac output fluctuations. Dose linearity was also assessed. The system response to dose was verified to be linear within the range 2-500 MU. Output factors matched very well pinpoint chamber measurements performed in the same experimental conditions with a maximum local percentage difference of 0.4%. Furthermore, the 2D Array sensitivity to millimetric collimator positional changes and to perturbation effect of irradiated area was tested. The comparison with ion chamber data carried out in water was very satisfying. Finally, measurements of wedge-modulated fields and IMRT beam sequence matched very well ion chamber dose profiles acquired in a water tank. The extensive tests performed in this investigation show that the 2D Array Seven29 is a reliable and accurate dosimeter and that it could be a useful tool for the quality assurance and the verification of radiotherapy plans.

The role of transplantation in small hepatocellular carcinoma complicating cirrhosis of the liver.

Of 176 hepatic transplants performed from 1986 to December 1992, 27 patients had small hepatocellular carcinoma (< or = 5 centimeters) complicating cirrhosis of the liver. All patients were asymptomatic for the hepatic malignancy and the diagnosis was established in each instance preoperatively by means of serial sonographic scans and alpha-fetoprotein levels. Cirrhosis was classified as Child's A in eight instances, as Child's B in 16 and Child C's in three. The cause was alcoholic in three patients, posthepatitic in 21 patients (eight hepatitis B virus [HBV] positive and 13 hepatitis C virus [HCV] positive) and undetermined in three. The in-hospital mortality rate was 11 percent (three of 27). Additionally, five patients died at different intervals after transplantation: only two died of neoplastic recurrence at 12 and 32 months, respectively (7.4 percent rate). Actuarial survival rates were 82 percent at one year and 71 percent at three years, with a mean follow-up period of 32 months (range six to 78 months). Morbidity related to the procedure was a relevant problem: 21 percent of the patients had prompt resumption of normal life while 37 percent required repeated hospitalization and 42 percent required strict control on an outpatient basis. The most frequent problem was HBV or HCV reinfection of the grafted liver, which occurred in 42 percent. Based on this experience, transplantation of the liver has shown an excellent oncologic accuracy for small hepatocellular carcinoma in cirrhosis of the liver, thus representing the most rational surgical procedure for patients with Child's B and Child's C cirrhosis classification. The relevant mortality and morbidity rates, strictly related to this procedure, suggest other options as more appropriate in those with Child A cirrhosis at this time.

Responsiveness to 'autoreceptor' doses of apomorphine inversely correlated with the firing rate of dopaminergic A9 neurons: action of baclofen.

Supersensitivity of dopamine (DA) autoreceptors develops soon after acute treatments with baclofen or gamma-butyrolactone, two drugs which suppress DA neuronal firing. We have hypothesized that this effect might reflect a condition associated with the low firing rate of DA cells induced by such treatments rather than a long-term adaptive modification of DA receptor sensitivity. In this study we show that the degree of the intravenous apomorphine-induced inhibition of A9-DA neurons is inversely correlated to the basal firing rate of these neurons. When administered after baclofen, apomorphine further reduced DA cell activities in a manner proportional to the predrug firing rate, as in control rats. Since the minute doses of apomorphine which were used are thought to selectively activate DA autoreceptors, our finding may indicate that DA autoreceptor stimulation is more effective when the activity of the DA neurons is low, or it is decreased by drugs such as baclofen.

Resection versus pericystectomy in the treatment of hydatidosis of the liver.

The surgical treatment of 87 hepatic cysts from Echinococcus granulosus in 42 patients has been presented. The importance of determining the features of the cysts in each patient (age, number, location, and relation with vasculobiliary structures) in order to carry out the most appropriate treatment was stressed. Radical surgery was preferred because marsupialization, a conservative technique still widely used, has a high complication rate (60 percent in this study) and a prolonged recovery time. Arguments for and against cystopericystectomy and hepatic resections have been discussed. It is noteworthy that excellent results have been observed after hepatic resection when it was performed in selected patients.

Is thrombocytopenia in liver failure dependent on an inadequate synthesis of thrombopoietic stimulating factor by the liver?

Thrombocytopenia in liver diseases has been considered secondary to portal hypertension or to a consumption mechanism associated with fibrinolytic disorders. Several conflicting clinical reports and evidence from experimental models justify the above mentioned mechanisms only in part. We propose that thrombocytopenia may be consequent to an inadequate synthesis of a factor stimulating thrombopoiesis produced by the liver.

The role of donor and recipient factors in initial renal graft non-function.

ATN is a deleterious problem in the outcome of kidney transplantation. This complication is usually related to multiple factors including donor parameters, surgical technique, ischemic time, and recipient variables. In order to develop prophylactic measures, out of 430 kidney transplants performed in our Department, a series of 90 consecutive cadaveric renal allografts has been considered in this study. The overall incidence of IGNF was 23/90 (25.5%). Kidneys from MOD revealed a lower rate of IGNF (7/35 = 20%) when compared with organs from SOD (16/55 = 29%, P = NS). No difference was noted when kidneys were removed together with heart and/or liver and/or pancreas. Out of the donor factors, only CID was significant (17 +/- 9 hours in IGNF v 11 +/- 10 hours in patients with IGF, P = less than .05). Analysis of data concerning the fate of paired kidneys revealed two cases of IGNF in both kidneys from the same donor v 14 cases of IGNF in only one of the two paired grafts (P = NS). We conclude that: 1. Donor factors are clearly associated with a minority of IGNF. 2. The introduction of multiorgan procurement programs does not complicate early function. 3. Recipient factors (immunological events and intraoperative fluid management) provides important additive effects on initial graft nonfunction.

[Carotid stenosis with contralateral occlusion. Surgical indications and results]. / Stenosi carotidea con occlusione controlaterale. Indicazioni chirurgiche e risultati.

Recent American and European trials have clearly defined that surgery provides best treatment for unilateral critical stenosis of internal carotid artery. Isolated reports seem to confirm this trend also in cases with carotid critical stenosis with controlateral occlusion, even if a major surgical risk may be expected. In our experience in the last two years, out of 96 carotid enderterectomies 20 presented a controlateral occlusion. After routine pre-operative assessment, with particular regard to DSA "cross-filling" study, intervention has been performed under general anesthesia with BP+EEG cerebral monitoring in both groups of patients. In the non occluded group temporary shunt has been used in 19.7% of cases, in occluded the incident of shunting was 40%. Operative morbidity and mortality in the second group was surprisingly absent, with cumulative 4.1% complication rate. Our experience confirms that risks and results in carotid endoarterectomy are similar in both groups of patients.

[Transhepatic percutaneous cholangiography with the Chiba needle in diagnosis of cholestasis]. / La colangiografia percutanea transepatica con ago di Chiba nella diagnostica delle colestasi.

A technique originally described by Okuda has been employed to study 78 patients suffering from cholestatic syndrome. Visualization of the biliary system was obtained in 70 (89.7%). Of these, 65 presented dilatation of the bile ways whereas in 5, the biliary tree was normal. The 8 cases in which no visualization was obtained were later examined with other techniques and 6 proved to be suffering from intrahepatic cholestasis. In patients with extrahepatic obstruction, the biliary system was visualized in 97%, while in intrahepatic cholestasis, the percentage was 45.5%. The main indication for PTC is the speed at which intrahepatic cholestasis can be distinguished from the extrahepatic type; in the second event, it always pinpoints the site of the impediment, though less frequently the nature of the lesion and its extent. No complications requiring emergency laparotomy were ever encountered. Percutaneous transhepatic cholangiography with Chiba needle is a simple, reliable inexpensive method which gives excellent results in the study of patients with cholestatic syndrome.

[Thoracic outlet syndromes. Arteriographic aspects]. / Sindromi dello stretto superiore del torace. Quadri arteriografici.

Chest outlet syndromes are characterized by pain symptomatology caused by (congenital or acquired reasons) compression of the vasculo-nervous bundle. After a brief mention of the anatomy of the question, the indications and angiographic technique are reported, special reference being made to certain positions and dynamic tests which increase symptomatology and highlight arteriographic findings. These are clearly identifiable in the pictures and offer documentary evidence of the cervical rib syndrome, scalenus syndrome, small pectoral syndrome, the hyperabduction syndrome and the costoclavicular syndrome. Differential diagnosis should consider a number of painful syndromes of the upper extremity of purely neurological interest (involvement of the brachial plexus). Vascular diseases such as arteriosclerosis, Takayasu's disease, etc., osteo-myo-articular and ORL sector diseases should also be taken into account. Arteriography is able to identify with precision the causes of the clinical syndrome and to guide surgical exploration of the supraclavicular fossa with excellent chances of success.

[The testis in a 46, XX male. Apropos of an ultrastructural examination]. / Le testicule chez l'homme 46 XX. A propos d'une observation ultrastructurale.

The ultrastructure of a testicular biopsy was carried out in a man with 46 XX chromosomes who had a masculine phenotype and in whom the hormone levels showed that the interstitial tissue of the gland was functioning well. Observations showed that the exocrine appearance of the testis was comparable to that described in Klinefelter's syndrome, namely germinal aplasia with invasion by Sertoli cells. On the other hand the interstitial glandular tissue showed morphological characteristics associated with normal androgen activity, which is unusual to find in Klinefelter's syndrome. Lipid inclusions, pigmentation and Reinke cristalloids were found. The cytogenetic techniques that happened to be used did not manage to show up even a small fragment of the Y chromosome. Various theories have been considered to explain the constitution of such a phenotype with this chromosome abnormality.

Nicotine and cotinine affect the release of vasoactive factors by trophoblast cells and human umbilical vein endothelial cells.

OBJECTIVE: To examine nicotine (N) and cotinine (C) effects on trophoblast cells (TCs) and human umbilical vein endothelial cells (HUVEC) secretion of soluble fms-like tyrosine kinase (sFlt-1), soluble endoglin (sENG), placental growth factor (PlGF), transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF). STUDY DESIGN: Human placentas and umbilical cords were collected from uncomplicated pregnancies at term from a total of 24 non-smoking women with a history of normal blood pressure. TCs and HUVEC were cultured for 24 h with C or N (from 10(-12) to 10(-7) M). MAIN OUTCOME MEASURES: sFlt-1, sENG, PlGF, TGF-beta and VEGF release and messenger RNA (mRNA) expression were evaluated by ELISA and real-time polymerase chain reaction (PCR), respectively. RESULTS: N and C reduced sFlt-1, sENG and PlGF release by TCs and TGF-beta release by HUVEC. Conversely, N and C increased PlGF secretion, while N alone increased sFlt-1 release by HUVEC. N and C were able to modulate VEGF mRNA expression in HUVEC. CONCLUSIONS: Our results suggest that N and C affect the balance of some important vasoactive factors released by TCs and HUVEC. This might be one of the possible mechanism through which smoke reduces the risk of hypertensive disorders during pregnancy as well as contributes to the well known detrimental effects of smoking on fetal development.