Effects of Lactobacillus rhamnosus GG on early postoperative outcome after pylorus-preserving pancreatoduodenectomy: a randomized trial.

OBJECTIVE: Pancreatoduodenectomy (PPPD) remains one of the most complex surgical procedures with high complication rates. Infectious complications, postoperative ileus and delayed gastric emptying in the perioperative period have a significant impact on the recovery from the treatment. Probiotics (PB) are known to have a beneficial effect as supportive therapy in major abdominal surgery but the evidence in pancreatic surgery is still limited. The aim of the study was to assess the influence of postoperative administration of PB on the early outcomes after PPPD. PATIENTS AND METHODS: Forty patients undergoing pylorus-preserving PPPD were enrolled to prospective trial and randomized in two groups: A - control group (n=20) receiving standard nutrition and B - probiotic group (n=20) treated additionally with Lactobacillus rahmnosus GG (L. rhamnosus GG) in the postoperative period from the day of the surgery for 30 days. Gastrointestinal motility, infection complications, length of hospital stay, and mortality were compared in the perioperative period and during 2 follow-up (i.e., after 14 and 30 days). RESULTS: There were no significant differences in mortality and infectious complications between groups. The length of hospital stay was shorter in the probiotic group compared to control (10 days vs. 8, respectively). The positive effect of L. rhamnosus GG on gastrointestinal tract's motility was observed, including earlier recurrence of postoperative bowel movements (group B: after 3.75 days vs. group A: 2.15 days), passing gasses (group B after 4 days vs. group A 2.9 days) and the first postoperative stool (group B after 5.84 days vs. group A 3.85 days). L. rhamnosus GG improved the appetite in postoperative day 1, 3, 5, 7 and 30 days after the surgery. CONCLUSIONS: L. rhamnosus GG improves the function of the gastrointestinal tract after major pancreatic surgery and may reduce the length of hospital stay.

Does the septic shock interfere experimental acute pancreatitis in rats?

INTRODUCTION: Acute pancreatitis is a disease involving pro-inflammatory mediators. Two complex and multifactorial pathogenetic ways lead to edematous or necrotizing pancreatitis. The course of the disease is thought to be the consequence of an acute inflammatory response. AIM: The authors examined the impact of Escherichia coli LPS on the acute cerulein pancreatitis in rats. METHODS: The study was performed on rats using the ceruleine pancreatitis model. The activation status of polymorphonuclear cells, blood IL-6 concentration, oxidative stress parameters, pancreatic enzymes concentration and microscopic alterations were determined at 5th and 9th h observations. RESULTS: In acute pancreatitis and acute pancreatitis with LPS groups, the peripheral polymorphonuclear cells activity was lower than in control one. Authors noticed the same neutrophil activation in acute pancreatitis after lipopolysaccharide administration although the peripheral blood polymorphonuclear cells count was significantly higher at the 9th h observation. LPS neither changed the oxidative stress within pancreatic gland, nor amylase or serum lipase activity. LPS given to acute pancreatitis animals resulted in significant increase of serum IL-6 concentration at 5th observation turning normal after 9th h. CONCLUSIONS: Collected data supports thesis of early polymorphonuclear cells involvement in acute pancreatitis and oxidative stress evidence in pancreatic parenchyma. However, results did not reveal that administration of LPS amplified inflammatory response during the course of acute pancreatitis.

Organ microcirculatory disturbances in experimental acute pancreatitis. A role of nitric oxide.

Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis (AP). The aim of the study was to investigate an influence of L-arginine (nitric oxide substrate) and N(G)-nitro-L-arginine (L-NNA, nitric oxide synthase inhibitor) on organ microcirculation in experimental acute pancreatitis induced by four consecutive intraperitoneal cerulein injections (15 microg/kg/h). The microcirculation of pancreas, liver, kidney, stomach, colon and skeletal muscle was measured by laser Doppler flowmeter. Serum interleukin 6 and hematocrit levels were analyzed. AP resulted in a significant drop of microperfusion in all examined organ. L-arginine administration (2 x 100 mg/kg) improved the microcirculation in the pancreas, liver, kidney, colon and skeletal muscle, and lowered hematocrit levels. L-NNA treatment (2 x 25 mg/kg) caused aggravation of edematous AP to the necrotizing situation, and increased IL-6 and hematocrit levels. A further reduction of blood perfusion was noted in the stomach only. It is concluded that L-arginine administration has a positive influence on organ microcirculatory disturbances accompanying experimental cerulein-induced AP. NO inhibition aggravates the course of pancreatitis.

Lichtenstein inguinal hernioplasty using butyl-2-cyanoacrylate versus sutures. Preliminary experience of a prospective randomized trial.

The Lichtenstein hernioplasty has become a popular method in inguinal hernia repair. This study compared two methods of mesh fixation and wound closure. Forty-six men with unilateral inguinal hernia were randomized into two groups. In the control group polypropylene mesh was anchored with 3/0 Dexon sutures, fascia and skin were closed with sutures 3/0 Dexon and 3/0 Monosof. In the study group, the mesh was secured with butyl-2-cyanoacrylate adhesive and the fascia and skin were also glued with the adhesive. The costs of materials, duration of the operation, amount of postoperative analgesic doses, pain score after the first and the 7th postoperative day and return to daily activity were recorded. No recurrences during the mean follow-up of 4.7 months were observed and the cosmetic effect was very good. In the study group with tissue adhesive the patients had significantly lower pain score after the first postoperative day and had a tendency to require less analgetic doses and to return earlier to their daily activity. Duration of the operation was similar in both groups. The cost of sutures and tissue adhesive used in both procedures was comparable. The use of tissue adhesive in mesh fixation and wound closure seems to be a promising technique in Lichtenstein hernia repair.

Prophylactic submucosal saline-adrenaline injection in colonoscopic polypectomy: prospective randomized study.

BACKGROUND: Endoscopic polypectomy is a standard method of treatment of gastrointestinal polyps, but is associated with substantial risk of complications. The most common is hemorrhage, the rate of which varied between 0.3%, and 6%. Various prophylactic techniques have been used to reduce this incidence. The aim of this study was to establish whether the prophylactic injection of adrenaline-saline solution reduces the risk of postpolypectomy bleeding in colonoscopic polypectomy. METHODS: Between May 2000 and June 2002, patients with colorectal polyps of size > or =1 cm were randomized to receive submucosal epinephrine injection (group A) or no injection (group B). The polypectomies were carried out using the conventional method. In group A, epinephrine (1/10,000) was injected into the stalk or base of the polyp. The patients were observed for complications. RESULTS: A total of 69 patients with 100 polyps were enrolled in this study: n = 50 in group A, and n = 50 in group B, according to randomization. There were a total of nine episodes of postpolypectomy hemorrhage, one in the epinephrine group and eight in the control group (1/50 vs 8/50, p < 0.05). The bleeding correlated with the size of the polyps and the diameter of the stalks. CONCLUSIONS: Epinephrine injection prior to colonoscopic polypectomy is effective in preventing bleeding.

Synthesis of new derivatives of bis-3(4-R-delta2-1,2,4-triazolin-5-one).

In the reaction of oxalic acid hydrazide with isocyanates, new derivatives of semicarbazide were obtained [I-XII]. Cyclization of these derivatives with an aqueous 2% sodium hydroxide led to formation of new derivatives of delta2-1,2,4-triazolin-5-one [XIII-XXIV].

[Management of postoperative pancreatic fistula resistant to octreotide therapy]. / Postepowanie z pooperacyjnymi przetokami trzustkowymi opornymi na leczenie oktreotydem.

Pancreatic fistula is a rare postoperative complication, usually occurring after pancreatic surgery. Majority of them heal spontaneously, some patients require somatostatin/octreotide treatment. The authors have presented 11 patients with postoperative pancreatic fistula, in whom octreotide therapy in dose of 0.1 mg t.i.d./10 days has been ineffective. The causes of pancreatic fistula have been as follows: necrosectomy of the infected pancreatic necrosis--5 patients, distal pancreatic resection--2 patients, insulinoma enucleation--2 patients, gastrectomy with partial pancreatectomy--2 patients. In 9 patients endoscopic stenting of the main pancreatic duct has been performed. In remained 2 patients after Roux-en-Y gastrectomy the endoscopic access to Vater papilla has been impossible and the patients have received one intramuscular injection of long acting somatostatin analogue. In 8 of 9 patients with pancreatic stenting and in two patients after gastrectomy the fistula has been closed within the period of 6-17 days. In one patient after the necrosectomy the prosthesis implacement has been ineffective. This patient has been successfully treated with two additional injections of long acting somatostatin analogue (one injection/14 days). Authors have concluded that endoscopic pancreatic stenting has been an effective method of treatment of the postoperative pancreatic fistula, resistant to octreotide therapy. In some cases, additional administration of long acting somatostatin analogue has been necessary.

Synthesis of 1-(3-aminopropyl)-4-phenyl-1,2,4-triazolin-5-one and 1-(3-aminopropyl)-3,4-diphenyl-1,2,4-triazolin-5-one.

The reaction of 4-phenyl-1,2,4-triazolin-5-one [Ia] and 3,4-diphenyl-1,2,4-triazolin-5-one [Ib] with 1-bromo-3-chloropropane was carried out. The obtained compounds [IIa, b] were subjected to the reaction with secondary amines and ethylenediamine with resulted in 1-(3-aminopropyl)-1,2,4-triazolin-5-one derivatives.

A repository of 14 PCR-loci Italian gene frequencies in the World Wide Web.

A collection of 6830 typing results produced by the Immunohematology Laboratory at the UCSC, pertaining to 11 STRs (FES/FPS, vWA31, HUMTH01, F13A1, MBP, D21S11, D7S460, D18S51, CD4, TPOX, CSF1PO) and 3 AmpFLPs (D1S80, APO-B, COL2A1), is publicly available as an electronic archive at a website.

Synthesis of 1-(3-amino-2-hydroksypropyl)-4-phenyl-1,2,4-triazolin-5-one and 1-(3-amino-2-hydroksypropyl)-3,4-diphenyl-1,2,4-triazolin-5-one derivatives.

In the reaction of 4-phenyl-1,2,4-triazolin-5-one [Ia] and 3,4-diphenyl-1,2,4-triazolin-5-one [Ib] with 1-chloro-2,3-epoksypropane, the respective derivatives of 1-(2,3-epoksypropane)-4-phenyl-1,2,4-triazolin-5-one [IIa] and 1-(2,3-epoksypropane)-3,4-diphenyl-1,2,4-triazolin-5-one [IIb] were obtained. Then these compounds were converted into the corresponding aminoalkanol derivatives of 1,2,4-triazolin-5-one [IIIa, b-VIIIa, b] in reaction with secondary amines. The new compounds affected significantly the central nervous system of mice.

Synthesis of aminomethyl derivatives of 4-phenyl-1,2,4-triazolin-5-one-1-acetic acid amide and 3,4-diphenyl-1,2,4-triazolin-5-one-1-acetic acid amide.

Ehtyl esters of 4-phenyl-1,2,4-triazolin-5-one-1-acetic acid and 3,4-diphenyl-1,2,4-triazolin-5-one-1-acetic acid were transformed into the corresponding amides [Ia, b]. The aminomethylation reactions afforded Mannich bases [IIa, b-VIa, b] exhibiting the expected pharmacological effects.

Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome.

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ ("naive" helper T cells, suppressor-inducer), CD45RA+CD8+ ("naive" suppressor T cells, suppressor-effector), CD45RO+CD4+ ("memory" helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-gamma, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18+/-0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05+/-0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2+/-0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82+/-0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85+/-0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5+/-0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS.

[Does the changed Th1/Th2 activity in children with the assessment of body water in children with nephrotic syndrome: initial results]. / Czy zmieniona aktywnosc limfocytów Th1/Th2 u dzieci z zespolem nerczycowym moze byc wskaznikiem reaktywnosci na leczenie?

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity(SS) or resistance(SR). Activity of Th1 and Th2 cells was defined by the production of IL-2, IFN-gamma and IL-4, IL-10 (ELISA), respectively, in the supernatants of the culture of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double or triple colour flow cytometry. In SS children with NS we found the cytokine synthesis indicating the predominance of Th2 activity. We conclude that prior to treatment the Th1 and Th2 cell activity provides a useful tool to evaluate the probability of steroid sensitivity in patients with primary NS.

Synthesis of new derivatives of 3-benzyl-4-R-delta 2-1,2,4-triazolin-5-one and 3,3'-methylidyne bis(4-R-1,2,4-delta 2-triazolin-5-one).

In the reaction of phenylacetic acid hydrazide or malonic acid hydrazide with isocyanates, new derivatives of semicarbazide were obtained [I-VIII]. Cyclization of these derivatives with a aqueous 2% sodium hydroxide led to the formation of new derivatives of delta 2-1,2,4-triazolin-5-one [IX-XVI]. Some of them were investigated pharmacologically on the central nervous system in mice.

Nitric oxide, heparin and procaine treatment in experimental ceruleine-induced acute pancreatitis in rats.

The aim of the study was to investigate the impact of L-arginine (nitric oxide donor), L-NNA (NO synthase inhibitor), heparin and procaine on the pancreas' microcirculation, serum interleukin 6 (IL-6) level, and microscopic alterations of the pancreatic gland in acute pancreatitis (AP) in rats. AP was induced by 4 i.p. injections of cerulein (15 micrograms/kg/h). Microcirculatory values of the pancreas were measured by means of laser Doppler flowmetry 5 h after the first cerulein injection. Remarkable morphologic changes in the pancreas, including parenchymal necrosis, an elevation of serum IL-6 activity, and significant drop of pancreatic capillary perfusion was observed in rats with NO synthase inhibition. L-arginine improved the pancreatic microcirculation but worsened the microscopic alterations within the pancreas. Heparin had a beneficial effect on the microcirculatory values, serum IL-6 activity, and morphologic changes. Procaine had no effect on the course of AP. Authors conclude that heparin, improving the pancreatic capillary blood perfusion, may be considered as a promising therapeutic agent in acute pancreatitis.

Heparin and nitric oxide treatment in experimental acute pancreatitis in rats.

The aim of this study was to investigate the impact of L-arginine (nitric oxide synthase substrate), L-NG-nitro-L-arginine (nitric oxide synthase inhibitor), and heparin on the pancreas microcirculation, serum IL-6 level and microscopic alterations of the pancreas in acute pancreatitis in rats. Acute pancreatitis was induced by 4 i.p. injections of cerulein (15mg/kg). Microcirculatory values were measured by means of laser Doppler flowmetry 5 h after the first cerulein injection. Remarkable histopathological changes in the pancreas, including parenchymal necrosis, an elevation of serum IL-6 level, and a significant drop of pancreatic capillary perfusion was observed in rats with nitric oxide synthase inhibition. L-arginine improved the pancreatic microcirculation but worsened the microscopic alterations within the pancreas. Heparin had a beneficial effect on the microcirculatory values, serum IL-6 concentration, and morphologic changes. Authors conclude that inhibition of nitric oxide synthase aggravates acute pancreatitis. L-arginine treatment improves pancreatic perfusion but potentiates morphological alterations. Heparin, improving the microcirculation and inflammatory changes within the pancreatic gland, may be considered as a promising therapeutic agent in acute pancreatitis.

Clinal variation in the nuclear DNA of Europeans.

Allele frequencies are clinally distributed for many protein polymorphisms in Europe, suggesting that the current populations are derived from an ancestral group that expanded from the Near East. It is not yet fully established whether that expansion took place during the Neolithic or earlier or whether the detectable protein variation faithfully reflects the underlying molecular variation. In this study we address the latter question by describing geographic patterns of genetic diversity at seven highly polymorphic DNA markers. Two of these markers are minisatellites, four are microsatellites, and the seventh is a locus of the HLA system. By analyzing a database of 304 samples, with more than 130,000 chromosomes, we found evidence for a major clinal component of genetic variation. At most loci spatially close populations resemble each other genetically, and the degree of genetic similarity, as measured by spatial autocorrelation statistics, decreases at increasing distances. The observed patterns of molecular variation do not seem to differ qualitatively from those identified for protein polymorphisms. This suggest that low levels of population structuring, described in some mitochondrial DNA studies, may reflect different evolutionary histories for nuclear and maternally inherited markers or, alternatively, that spatial patterns of mitochondrial DNA variation may need more sensitive statistical methods to be recognized.

Increased forensic efficiency of a STR-based Y-specific haplotype by addition of the highly polymorphic DYS385 locus.

The polymorphic short tandem repeat (STR) locus DYS385 mapping to the male-specific region of human Y chromosome, was used to reinvestigate 125 unrelated Italian males, from our data archive, who had been previously typed for 7 different Y-specific STRs (DYS19, DYS389 I and II, DYS390, DYS391, DYS392, DYS393), defining a haplotype now widely adopted in the forensic context. The aim of this study was to improve the information value of the original haplotype in view of its application to issues of personal identification and parental analysis. DYS385 proved to be highly polymorphic (94.5% gene diversity) and the overall individualization capacity of the 8-loci haplotype was raised to 93.6%, with 117 unique assets out of 125 tested samples.

[Three sets of twins in three successive generations through the maternal line]. / Tre coppie di gemelle in tre generazioni successive nate da madri gemelle.

It is generally held that there are genetic factors for dizygotic (DZ) twinning, but the pattern of inheritance is far from clear. We report on a rare pedigree with three sets of spontaneous DZ female twin births in three successive generations. To our knowledge no similar pedigrees have been reported in literature. Zygosity determination in three pairs of twins was performed with ABO, MN and Rh blood groups from erythrocytes and with STR analysis from samples of saliva. In our pedigree, the direct transmission of the DZ twinning through the maternal line seems show an autosomal dominant pattern of inheritance. We believe that the inheritance of DZ twinning appears to be recessive in most case and autosomal dominant only in rare instances. It is plausible with the hypothesis that the expression of the dizygotic twinning trait in a mother shows a genetic heterogeneity.