High-dose gynecologic endocavitary brachytherapy. Technical and dosimetric aspects

The technical and dosimetric aspects are presented of high-dose intracavitary brachytherapy in gynecology. Fifty-five patients (203 insertions) were examined over two years with a remote loading Selectron HDR 60Co unit installed in a dedicated bunker. The dose to the rectal and bladder markers on AP and LL films was calculated before every irradiation, in order to allow the necessary corrections to be made. Uniform irradiation conditions were obtained at each treatment set-up for both tumoral target and bladder and rectal doses. High-dose intracavitary brachytherapy proved to be a safe, reliable and versatile method from the technical and dosimetric point of view both in the treatment of unoperated gynecological malignancies and in postoperative therapy.     

Activation of extracellular signal-regulated kinase in proliferative glomerulonephritis in rats.

Multiple extracellular mitogens are involved in the pathogenesis of proliferative forms of glomerulonephritis (GN). In vitro studies demonstrate the pivotal role of extracellular signal-regulated kinase (ERK) in the regulation of cellular proliferation in response to extracellular mitogens. In this study, we examined whether this kinase, as a convergence point of mitogenic stimuli, is activated in proliferative GN in vivo. Two different proliferative forms of anti-glomerular basal membrane (GBM) GN in rats were induced and whole cortical tissue as well as isolated glomeruli examined using kinase activity assays and Western blot analysis. Administration of rabbit anti-rat GBM serum to rats, preimmunized with rabbit IgG, induced an accelerated crescentic anti-GBM GN. A significant increase in cortical, and more dramatically glomerular ERK activity was detected at 1, 3, and 7 d after induction of GN. Immunization of Wistar-Kyoto rats with bovine GBM also induced a crescentic anti-GBM GN with an increase of renal cortical ERK activity after 4, 6, and 8 wk. ERK is phosphorylated and activated by the MAP kinase/ERK kinase (MEK). We detected a significant increase in the expression of glomerular MEK in the accelerated form of anti-GBM GN, providing a possible mechanism of long-term activation of ERK in this disease model. In contrast to ERK, activation of stress-activated protein kinase was only detectable at early stages of proliferative GN, indicating these related kinases to serve distinct roles in the pathogenesis of GN. Our observations point to ERK as a putative mediator of the proliferative response to immune injury in GN and suggest that upregulation of MEK is involved in the long-term regulation of ERK in vivo.     

Cutis laxa,exocrine pancreatic insufficiency and altered cellular metabolomics as additional symptoms in a new patient with ATP6AP1-CDG

Congenital disorders of glycosylation (CDG) are genetic defects in the glycoconjugate biosynthesis. > 100 types of CDG are known, most of them cause multi-organ diseases. Here we describe a boy whose leading symptoms comprise cutis laxa, pancreatic insufficiency and hepatosplenomegaly. Whole exome sequencing identified the novel hemizygous mutation c.542 T > G (p.L181R) in the X-linked ATP6AP1, an accessory protein of the mammalian vacuolar H⁺-ATPase, which led to a general N-glycosylation deficiency. Studies of serum N-glycans revealed reduction of complex sialylated and appearance of truncated diantennary structures. Proliferation of the patient's fibroblasts was significantly reduced and doubling time prolonged. Additionally, there were alterations in the fibroblasts' amino acid levels and the acylcarnitine composition. Especially, short-chain species were reduced, whereas several medium- to long-chain acylcarnitines (C14-OH to C18) were elevated. Investigation of the main lipid classes revealed that total cholesterol was significantly enriched in the patient's fibroblasts at the expense of phophatidylcholine and phosphatidylethanolamine. Within the minor lipid species, hexosylceramide was reduced, while its immediate precursor ceramide was increased. Since catalase activity and ACOX3 expression in peroxisomes were reduced, we assume an ATP6AP1-dependent impact on the β-oxidation of fatty acids. These results help to understand the complex clinical characteristics of this new patient.     

A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

The functional His452Tyr polymorphism in the 5HT2A receptor has been described to be associated with verbal memory in healthy adults, with worse episodic memory performances in Tyr452 (T) carriers. The aim of our study was to investigate a possible effect of this polymorphism on memory performances in Alzheimer disease (AD). We enrolled 169 patients affected by probable AD. 5HT2A genotype was determined as previously described. According to their genotype, patients were divided in T carriers (?n = 111) and non-carriers (?n = 69). We evaluated the possible effect of 5HT2A polymorphism on verbal memory tasks. A one-way MANOVA analysis did not show a positive interaction between the two groups (?p > 0.05) at the baseline and at the follow-up. Nevertheless, the analyses of the single-task effect showed lower performances for non-T carriers only in Rey's recognition task. Recent data reported poorer memory performances in healthy subjects carrying the T variant, in age-dependent manner (no differences between T vs. nT carriers were observed for age >50 years). In our AD sample, we did not find significant differences in verbal memory scores in T vs. nT carriers while a significant difference was found only in attentional task. At variance with that in healthy subjects, no correlation has been found between memory profiles of AD patients and His452Tyr polymorphism.     

Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma

Background

Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.

Bucrylate treatment of bleeding gastric varices: 12 years' experience

BACKGROUND AND STUDY AIMS: For several years now there has been an increasingly widespread use of a tissue adhesive in the treatment of bleeding gastric varices to achieve rapid, safe control of hemostasis and prevent rebleeding. In this study we report on our experience with the use of Bucrylate (Hystoacryl) for the treatment of gastric varices over a period of more than a decade. PATIENTS AND METHODS: Since 1988, 174 cirrhotic patients with actively bleeding gastric varices have been admitted to our department, where they received emergency treatment with injections of Bucrylate. Any associated nonbleeding esophageal varices were subjected to traditional sclerotherapy in combination with the Bucrylate treatment. The gastric varices were subdivided into four distinct groups according to the method advocated by Sarin in 1989. The patients underwent weekly sclerotherapy sessions until their varices were eradicated, and the follow-up with a mean of 36 months (range 9-90 months) consisted of endoscopy at 3, 6, and 12 months during the first year and then yearly checks to confirm obliteration of the varices. RESULTS: The hemostasis (97.1%), early rebleeding (15.5%), and hospital mortality (19.5%) rates of the patients with bleeding gastric varices, treated with the tissue adhesive, were very similar to those of patients treated for esophageal varices over the same period (98.1%, 13.0%, and 16.4%, respectively). The most frequent cause of death at 30 days was liver failure (76% of cases), followed by hemorrhagic shock (8.8%), and other less frequent causes. Sclerotherapy achieved obliteration rate for gastric varices (70-75%) similar to that for esophageal varices in those patients with portal hypertension due to intrahepatic block (alcoholic and posthepatitis cirrhosis), but a rate of only 32% in the group of patients with prehepatic block (splenoportomesenteric thrombosis), where surgery proved more effective (69%). The medium- and long-term survival rates depended on the stability of the patients' liver conditions, on rapid, effective control of variceal hemostasis, and on complete, lasting obliteration of the gastric varices. CONCLUSIONS: The use of Bucrylate in emergency sclerotherapy achieved results in bleeding gastric varices on a par with those obtained in esophageal varices in cases of alcoholic and posthepatitis cirrhosis. The group of patients with portal hypertension due to prehepatic block (splenoportal thrombosis) showed no benefit from sclerotherapy in terms of obliteration of gastric varices, but benefited from elective surgery. The choice of the obliterating treatment indicated may be facilitated by classifying gastric varices into distinct groups on the basis of anatomicotopographic criteria.     

Positive end-expiratory pressure delays the progression of lung injury during ventilator strategies involving high airway pressure and lung overdistention

OBJECTIVE: Many studies have investigated the protective role of positive end-expiratory pressure (PEEP) on ventilator-induced lung injury. Most assessed lung injury in protocols involving different ventilation strategies applied for the same length of time. This study, however, set out to investigate the protective role of PEEP with respect to the time needed to reach similar levels of lung injury. DESIGN: Prospective, randomized laboratory animal investigation. SETTING: The University Laboratory of Ospedale Maggiore, Milano, IRCCS. SUBJECTS: Anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats. INTERVENTIONS: Three groups of five Sprague-Dawley rats were ventilated using zero end-expiratory pressure ZEEP (PEEP of 0 cm H(2)O) and PEEP of 3 and 6 cm H(2)O and a similar index of lung overdistension (Paw(p)/P(100) congruent with 1.1; where Paw(p) is peak airway pressure and P(100) is the pressure corresponding to total lung capacity). To obtain this, tidal volume was reduced depending on the PEEP. To reach similar levels of lung injury, we measured respiratory system elastance while ventilating the animals and killed them when respiratory system elastance was 150% of baseline. Once target respiratory system elastance was reached, the lung wet-to-dry ratio was obtained. RESULTS: Rats were ventilated with comparable high airway pressure (Paw(p) of 42.8 +/- 3.1, 43.5 +/- 2.6, and 46.2 +/- 4.4, respectively, for PEEP 0, 3, and 6) obtaining similar overdistension (Paw(p)/P(100) - index of overdistension: 1.17 +/- 0.2, 1.06 +/- 0.1, and 1.19 +/- 0.2). The respiratory system elastance target was reached and wet-to-dry ratio was not different in the three groups, suggesting a similar degree of lung damage. The time taken to achieve the target respiratory system elastance was three times longer with PEEP 3 and 6 (55 +/- 14 mins and 60 +/- 17) as compared with zero end-expiratory pressure (18 +/- 3 mins, p <.001). CONCLUSION: These findings confirm that PEEP is protective against ventilator-induced lung injury and may enable the clinician to "buy time" in the progression of lung injury.