Early dynamics of leptin plasma level in surgical critically ill patients. a prospective comparative study.

BACKGROUND: Leptin (LPT), a hormone secreted by adipocytes,plays a role in inflammation and infection. Our study aimed to characterize the early dynamics of LPT in comparison with CRP and IL-6 during systemic inflammatory response syndrome(SIRS) and sepsis in surgical patients. METHODS: Sixty patients were assigned into 3 equal groups:SIRS (SI) group with major abdominal elective surgery;sepsis (SE) group with community-acquired complicated intra-abdominal infection and controls (C). LPT, CRP and IL-6 were measured initially in all groups and repeated in groups SI and SE within 5 days after surgery (9 samples - 4 day 1, 2 day 2, 1 next 3 days). RESULTS: LPT increased at 12-24 hours in SI group, but stayed within normal range in SE group. CRP and IL-6 had higher values in SE group versus SI group with an early peak for IL-6 and a late peak for CRP. CONCLUSIONS: LPT has a different early dynamics during SIRS and sepsis. LPT measurement in association with CRP or IL-6 may be useful in the differential diagnosis and prognosis of surgical critical illness at different time courses.

Interleukin-15 protects from lethal apoptosis in vivo.

Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor beta and gamma chains. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T-cell apoptosis in vitro, depending on T-cell activation, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells. Studying whether and how IL-15 modulates distinct apoptosis pathways, we show here that apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and/or anti-IgM in activated human T and B cells in vitro is inhibited by IL-15 in a manner dependent on RNA synthesis. In vivo, anti-Fas-induced lethal multisystem apoptosis in mice is suppressed by a novel IL-15-IgG2b fusion protein. Only IL-15, but not IL-2, completely protected from lethal hepatic failure. Thus, IL-15 is a potent, general inhibitor of apoptosis in vitro and in vivo with intriguing therapeutic potential.

Expression Analysis of Platinum Sensitive and Resistant Epithelial Ovarian Cancer Patient Samples Reveals New Candidates for Targeted Therapies.

Ovarian cancer has the highest mortality rate of all gynecologic malignancies. Identification of new biomarkers is highly needed due to its late diagnosis and high recurrence rate. The objective of this study was to identify mechanisms of therapy resistance and potential biomarkers by analyzing mRNA and protein expression from samples derived from patients with platinum-sensitive and -resistant ovarian cancer (total cohort n = 53). The data revealed new candidates for targeted therapies, such as GREB1 and ROR2. We showed that the development of platinum resistance correlated with upregulation of ROR2, whereas GREB1 was downregulated. Moreover, we demonstrated that high levels of ROR2 in platinum-resistant samples were associated with upregulation of Wnt5a, STAT3 and NF-kB levels, suggesting that a crosstalk between the non-canonical Wnt5a-ROR2 and STAT3/NF-kB signaling pathways. Upregulation of ROR2, Wnt5a, STAT3 and NF-kB was further detected in a platinum-resistant cell-line model. The results of the present study provided insight into molecular mechanisms associated with platinum resistance that could be further investigated to improve treatment strategies in this clinically challenging gynecological cancer.

Abnormal contractile function due to induction of nitric oxide synthesis in rat cardiac myocytes follows exposure to activated macrophage-conditioned medium.

The mechanism by which soluble mediators of immune cell origin depress myocardial contractility, either globally as in systemic sepsis, or regionally in areas of inflammatory myocardial infiltrates, remains unclear. When freshly isolated ventricular myocytes from adult rat hearts were preincubated for at least 24 h in medium conditioned by endotoxin (LPS)-activated rat alveolar macrophages, their subsequent inotropic response to the beta-adrenergic agonist isoproterenol was reduced from 225 +/- 19% to 155 +/- 10% of the baseline amplitude of shortening (mean +/- SEM, P < 0.05). Neither baseline contractile function nor the contractile response to high extracellular calcium were affected. To determine whether an endogenous nitric-oxide (NO)-signaling pathway within ventricular myocytes was responsible for their decreased responsiveness to isoproterenol, the L-arginine analogue L-NMMA was added to the preincubation medium. While L-NMMA did not affect baseline contractile function or the response of control myocytes to isoproterenol, it completely restored the positive inotropic response to isoproterenol in myocytes preincubated in LPS-activated macrophage medium. Release of NO by ventricular myocytes following exposure to activated macrophage medium was detected as an increase in cGMP content in a reporter-cell (RFL-6) bioassay and also as increased nitrite content in myocyte-conditioned medium. Thus, the depressed contractile response of adult rat ventricular myocytes to beta-adrenergic agonists by a 24-h exposure to soluble inflammatory mediators is mediated at least in party by induction of an autocrine NO signaling pathway.

[Acute urinary retention in primary vaginal carcinoma: therapeutic approach]. / Retentie acuta de urina prin cancer de vagin: atitudine terapeutica.

Carcinoma of the vagina is a very rare disease. Primary vaginal carcinoma tends to spread by local invasion of the adjacent pelvic organs (without any kind of metastases) and secondarily through lymphatic channels. The aim of this report is to add observations concerning the surgical treatment of this rare occurrence of carcinoma. The 33-year old patient's history began with an acute urinary retention which imposed bladder catheterization. Local examination revealed a hard 3/3 cm large mass on the middle third of the anterior vaginal wall, invasive in the urinary bladder. Cystoscopic examination confirmed the tumor invasion in the trigone. Biopsy specimens of the tumor and histological examination showed carcinoma. Anterior pelvic exenteration with pelvic lymph nodes dissection and total colpectomy was performed and the patient received a continent urinary diversion to the skin (modified Indiana pouch), ovary transposition, vaginal reconstruction with gracilis myocutaneous flaps. Postoperative evolution was uneventful. Organ reconstruction surgery including continent urinary diversion, vaginal reconstruction will significantly improve the quality of life and don't change the body image of the patients after pelvic major surgical procedures such pelvic exenteration.

Vaccination with tumor cells engineered to secrete interleukin 2-immunoglobulin G fusion protein induces tumor rejection.

Here we provide proof that the injection of tumor cells engineered to secrete interleukin 2 (IL-2)-IgG chimeric proteins locally induces potent antitumor responses, which are more effective than tumor transfection with IL-2 alone. Murine plasmacytoma cells (J558L) were stably transfected with DNA coding for a human IL-2-IgG1 or a murine IL-2-IgG2b fusion protein and were injected s.c. into syngeneic BALB/c mice. Evaluation of tumor growth and rejection patterns showed that IL-2-IgG secretion by transfected J558L tumor cells induced their rejection in all animals tested, similar to the rejection of J558L cells engineered to secrete IL-2 alone, whereas treatment with parental cells was lethal. However, mice treated with IL-2-IgG-secreting J558L cells (human IL-2-IgG1 and murine IL-2-IgG2b) exhibited a significantly stronger tumor immunity against a later challenge with parental J558L cells than mice treated with IL-2-secreting tumor cells.

Biochemical changes in the rat brain associated with dinitrophenol-induced brain edema.

The present paper was designed to the study of cerebral edema induced by intracarotid infusion of dinitrophenol. The determinations included variations in three lysosomal enzymes (acid phosphatase, cathepsin C and beta-glucuronidase), Na+-K+-ATP-ase, changes in cerebral RNA and protein concentrations and the synthesis of these macromolecules in vitro. In experimental brain edema a drastic drop in the activity of lysosomal enzymes took place. The acid phosphatase decreased to less than 30% of controls. Cathepsin C and beta-glucuronidase were reduced about 30% and 50% of control levels respectively. Protein concentration in the cerebral tissue also decreased by more than 50%. The concentration of RNA, RNA synthesis, and the level of Na+-K+-ATP-ase remained unchanged. Protein synthesis was stimulated by 75% (against controls). All these phenomena were suppressed when the animals subjected to the action of dinitrophenol were concomitantly treated with the antiacidotic substance, tris (hydroxymethyl) aminomethane.

Antioxidant action of a new flavonic derivative in acute carbon tetrachloride intoxication.

The antioxidant potential of a new flavonic derivative named conventionally theophylline-rutoside [TR-1722] was estimated by the measurement of G-6-Pase activity (marker enzyme for the endoplasmic reticulum), catalase activity (enzyme involved in the antioxidant defence process), and total -SH groups from the hepatic homogenate, using CCl4 as a free radical generating model. To show changes in the permeability of the hepatocyte membrane, the activity of lactate dehydrogenase (LDH) in plasma was determined. The obtained results suggest that TR-1722 acts by curtailing both lipid peroxidation and alkylation processes.

Ultrarapid induction.

We report 250 rapid induction anesthesias performed for the purpose of preventing regurgitation and vomiting in patients with full stomach. The anesthetic technique includes administration of morphine 20 mg and droperidol 5 mg intravenously 10-15 minutes before induction, a voluntary air hyperventilation at the anesthetist's command, during which induction drugs are introduced and an induction with a mixture containing suxamethonium 2 mg/kg and thiopentone 1.4 mg/kg, administered within 1-2 seconds. Eighteen seconds after the onset of injection the loss of lid reflex is observed followed 7 seconds later by masseter muscle relaxation. Within the following 5-10 seconds intubation is carried out in full fasciculation process, before cardia relaxation. With this technique, a mean intubation time of 35 seconds is achieved. The interval of maximum regurgitation risk is lowered to 15 seconds, so that ventilation by mask and cricoid pressure are no more necessary. The technique is indicated in the young and vigorous adult and contraindicated in the old and tainted patient, in coronary patients, in those with low heart output and slowing of circulation.

[Therapeutical options in lithiasic biliary fistula]. / Optiuni terapeutice în fistulele biliare litiazice.

Chronic lythiasic cholecystitis is a disease distinguished by the pathologic changes because of the chronic inflammation of the biliary extrahepatic tree. Sometimes these morphological changes are associated with internal biliary fistulas arising spontaneously in patients with advanced calculus cholecystitis. The vast majority of fistulas result from the adherence of the inflamed gallbladder or common bile duct to an adjacent viscus and erosion of the gallstones into the adherent organ. The authors analyze an amount of 43 patients with bilio-biliary and bilio-digestive lythiasic fistulas, caused by the long evolution of chronic lythiasic atrophic cholecystitis, for 126 cases which were operated in the Surgery Department of the Caritas Clinic Hospital along 20 years. In these 126 cases the surgical strategy was determinated by the method of dealing with the pericolecystitis sclerotic blocks, by the identification methods of the biliary elements and by the approach of the main billiary way and digestive loops injuries occurred after suppressing the fistulae. The surgical solutions adapted for each separate case and the advantages of the axial drainage of prostheting the surgical reconstructions of the main biliary way as well as the results obtained along this project, are in fact the aims of this presentation.

[Recessive hiccup of rare cause (compressive pleuro-pericardial lymphocele). Case report]. / Singultus rebel de cauza rara (Limfocel pleuro-pericardic compresiv cu evolutie lenta) prezentare de caz.

The authors discuss the case of a 40 year-old woman, which was performed surgery for a stenosant duodenal ulcer by bilateral troncular vagotomy and hemigastrectomy, using the Pean-Billroyh 1 anastomosis. Immediately after surgery untractable hicongh gradually set in which lasted over a 14 year, till the moment when a compressive pleuropericardic lymphocele, of the right phrenic nerve was revealed, a very long time growing cyst. After the surgical removal of the lymphocele was performed, which had compressed the right phrenic nerve, singultation totally disappeared, the patient has been monitorized through periodical medical checkings for more than 4 years. The period of 14 years when the patient constantly complained of steady untractable singultation has comprised 30 admission or more, to various surgical, gastroenterology and psychiatry wards. The patient was finally considered an incurable psychotic and was medically pensioned. The authors discuss a number of possible sequels of the initial gastric surgery which could have triggered untractable singultation, without being able to control them or totally ruling out the psychotic causes. There is natural suspicion cast of either existence or beginning of this cyst simultaneous with surgery since clinical tests and explorations were able to reveal it only after 14 years.

[Stenosing hypertrophic antromyopathy]. / Antromiopatia hipertrofica stenozanta.

The authors describe a case of insufficiency of gastric evacuation, due to the a very rare injury of the antrum which they called:--"hypertrophic and stenosing antromiopathiae". By similarity with the pilor hypertrophy, but without altering the pilor which is intact, the hypertrophy involves especially the gastric antrum, the muscular tunic--mainly the circular fibres in the absence of any acute or chronic inflammatory process. In the interstice between the muscular fibres, there appear collagen fibres in spiral disposition, probably in a contraction. Due to the similitude of the clinical syndrome, the described disease could be ranged among the stenosant diseases of the pyloric pole of the stomach. Out of these, more frequently pointed out, although very rare too, seems to be the pilor hypertrophy at adults. Mention must be made that the two diseases are completely different, because in the "Hypertrophic and stenosing antromiopathiae", the pilor is macroscopic and at the same time normal from the histopathologic aspect point of view.

[Intra-abdominal fibromatosis]. / Fibromatoza intraabdominala.

The authors describe three cases of intraabdominal fibromathosis: two cases with intraperithoneal location and another one with retroperithoneal location. All of them are benign noncapsulated tumours of the fibrous tissue with tendancy to local recurrence. Abdominal fibromathosis may determine any form of acute or chronic digestive manifestations. Only to the accuracy of the histo-pathological examination is due the diagnosis between fibromathosis and fibrosarcoma, reactive fibrosis, mixoma and nodular fasceitis. The surgical excision must not be economical and the association with radiant therapy must also be considered.

[Unusual hemorrhagic complication after surgery for severe generalized appendicular peritonitis]. / Complicatii hemoragice neobisnuite dupa o peritonita apendiculara grava operata.

The 22 year old male patient, was admitted in hospital for severe generalized peritonitis subsequent to acute perforated appendicitis and toxico-septic shock. On examination and relying on the previous history of the patient onset of the perforation was start assessed to have occurred some days earlier. Severe generalized, putrid peritonitis was found on surgery of the peritoneal cavity. Appendectomy was successfully carried out with a simple ligature of the appendix stump, and the ligature of the mezooappendix was performed without identifying the appendicular artery. Early in the postoperative stage there occurred diffuse bleeding localized in the peritoneal cavity. The source of the bleeding could not by found at the first reoperation. Subsequently the septic syndrome evolved simultaneously with the bleeding in a milder form, however, leading to growth in size of retroperitoneal hematoma. On marking the diagnosis, relying on CT examination, a new, second surgery was performed which afforded evacuation and drainage of the retroperitoneal hematoma. The authors have remarked and have tried to clear up the circumstances which had been conductive to the occurrence of hemorrhage, a thing absolutely unusual in the evolution of diffuse peritonitis by perforated acute appendicitis.

[Controlled stomach fistula for acute operated ulcer. Case report]. / Fistula gastrica dirijata pentru ulcer acut postoperator perforat. Prezentare de caz.

The authors analyze the case of a 65 old woman which was hospitalized for sigmoidian stenosant and haemorrhagical neoplasm, confined to the colic wall, without peritoneal or hepatic metastases, and without peritoneal or parietal invasion. Surgical management included sigmoidectomy and termino-terminal anastomosis for reconstructing intestinal transit followed by peritoneal drainage. In early postoperative stage the aspect of generalized peritonitis occurs and there is suspicion of anastomotic fistulae. On surgery, acute and perforated gastric ulcer is found, located in close vicinity to the cardia, on the anterior side of the stomach. Suture of the perforation is undertaken with drainage of the peritoneal cavity, but successfully because fistulization of the sutured perforation followed. Under the given circumstances controlled drainage of the gastric fistulae was carried out, using a Folley probe extended through the fistulae orifice and through the anterior abdominal wall, lateral to the median incision. The blowing of the intragastric balloon and the setting into tension of the gastric wall to the front abdominal wall allowed the sealing of the fistulae route but it took about three months. This technical contrivance has afforded good postoperative evolution and recovery of the patient, who after five years from surgery is in a good condition and has no subjective complaints.

[Metabolic effects of hypolipemic drugs on aged type 2 diabetes]. / Influenta terapiei hipolipemiante în reglarea metabolica a diabetului tip II la vârstnic.

There are multiple lipids anomalies on diabetes. IDDM has, because of insulin lack, increased levels of triglycerides and afferent lipoproteins. NIDDM, especially obese one, linked by insulinoresistance and hyperinsulinemia, has different and complex anomalies by quality and quantity. There is a specific shape for this anomalies named "B phenotype" with high cardiovascular risk: rise LDL-chol charged with TG and low level of HDL-chol. We searched lipoproteins levels and the effects of simvastatin on aged persons (after 60 years). We randomised 158 cases with obese type II diabetes on a case control study. We concluded that only 28% had high TG levels and 71.8% had low levels of HDL-chol. For HDL-chol this percent is higher over 60 years old group (88.75%) (p < 0.001). Cholesterol has no significant high levels (28.55%) (p < 0.5), and aged group has almost normal levels of cholesterol and triglycerides (p < 0.0001). We administered simvastatin (Zocor) on 86% cases, therapeutically doses, during a period of 6 months to one year. Making lipidograms initially, after 6 months and a year, we proved good effects of Zocor, on lipoproteins levels: rise levels of HDL-chol (p < 0.005), moderate effect on LDL-chol (p < 0.01). At the same time the treatment improving the glucose tolerability to both groups (p < 0.002).