Correlation between antimicrobial consumption and antimicrobial resistance of Pseudomonas aeruginosa in a hospital setting: a 10-year study.

WHAT IS KNOWN AND OBJECTIVE: Antimicrobial resistance is one of the greatest threats to human health. One of the most important factors leading to the emergence of resistant bacteria is overuse of antibiotics. The purpose of this study was to investigate the correlation between antimicrobial usage and bacterial resistance of Pseudomonas aeruginosa (P. aeruginosa) over a 10-year period in the Clinical Center Nis, one of the biggest tertiary care hospitals in Serbia. We focused on possible relationships between the consumption of carbapenems and beta-lactam antibiotics and the rates of resistance of P. aeruginosa to carbapenems. METHODS: We recorded utilization of antibiotics expressed as defined daily doses per 100 bed days (DBD). Bacterial resistance was reported as the percentage of resistant isolates (percentage of all resistant and intermediate resistant strains) among all tested isolates. RESULTS AND DISCUSSION: A significant increasing trend in resistance was seen in imipenem (P < 0·05, Spearman ρ = 0·758) and meropenem (P < 0·05, ρ = 0·745). We found a significant correlation between aminoglycoside consumption and resistance to amikacin (P < 0·01, Pearson r = 0·837) and gentamicin (P < 0·01, Pearson r = 0·827). The correlation between the consumption of carbapenems and resistance to imipenem in P. aeruginosa shows significance (P < 0·01, Pearson r = 0·795), whereas resistance to meropenem showed a trend towards significance (P > 0·05, Pearson r = 0·607). We found a very good correlation between the use of all beta-lactam and P. aeruginosa resistance to carbapenems (P < 0·01, Pearson r = 0·847 for imipenem and P < 0·05, Pearson r = 0·668 for meropenem). WHAT IS NEW AND CONCLUSION: Our data demonstrated a significant increase in antimicrobial resistance to carbapenems, significant correlations between the consumption of antibiotics, especially carbapenems and beta-lactams, and rates of antimicrobial resistance of P. aeruginosa to imipenem and meropenem.

Does the presence of an unerupted lower third molar influence the risk of mandibular angle and condylar fractures?

It has been suggested that unerupted lower third molars (M3) increase the fragility of the mandibular angle and simultaneously decrease the risk of condylar fracture. However, it is unknown whether this applies regardless of the direction and point of impact of the traumatic force. The aim of this study was to investigate the impact of an unerupted M3 on the fragility of the angle and condyle in terms of a force acting from different directions and affecting different regions of the mandible. Computed tomography scans of a human mandible and finite element methodology were used to obtain two three-dimensional models: a model with, and the other without an unerupted M3. A force of 2000N was applied to three different regions of the models: the symphysis, ipsilateral body, and contralateral body, respectively. When the force was applied to the mandibular body, the results revealed increased angle fragility in cases with unerupted M3. When the force was applied to the symphysis, the condyle region showed higher fragility, irrespective of the presence of an unerupted M3. In summary, fragility of the angle and condyle regions depends on the presence of an unerupted M3 and on the direction and point of impact of the force.

Monitoring of antibiotic consumption and development of resistance by enterobacteria in a tertiary care hospital.

WHAT IS KNOWN AND OBJECTIVE: Antibiotics are the most frequently used drugs in hospitalized patients, but studies have shown that the prescribed antibiotics may be inappropriate and may contribute to antibiotic resistance. We carried out a survey of antibiotic consumption and antibiotic resistance in our tertiary care university hospital, from 2005 to 2013. We focus on cephalosporins, one of the most prescribed groups of antibiotics in the tertiary health care. The objective was to identify any relationship between ceftriaxone consumption and resistance by enterobacteria. METHODS: Antibiotics consumption and antimicrobial resistance were monitored in the tertiary care university hospital from 2005 to 2013. Data on the use of antibiotics in surgical inpatients were obtained and expressed as defined daily doses per 100 bed days. Bacterial resistances were given as percentages of resistant isolates. RESULTS AND DISCUSSION: There was an increasing trend in cephalosporins consumption from 9·56 DBD (2005) to 23·32 DBD (2013), with ceftriaxone as the most frequently used cephalosporin, 3·6 DBD (2005) to 10·78 DBD (2013). E. coli and P. mirabilis resistance to ceftriaxone increased significantly from 22% in 2005 to 47% in 2013 and from 31% in 2005 to 60% in 2013, respectively. We found a significant correlation between ceftriaxone consumption and E. coli resistance (r = 0·895, P < 0·05). WHAT IS NEW AND CONCLUSION: Our study shows that cephalosporin consumption increased from 2005 to 2013, with ceftriaxone as the most prescribed antibiotic. E. coli and P. mirabilis resistance to ceftriaxone increased significantly over the study period. E. coli resistance increased with ceftriaxone consumption.

Paranasal sinus osteoma: is there any association with anatomical variations?

BACKGROUND: Developmental disturbances of the paranasal sinuses are proposed as the cause of osteoma. We examined whether such disturbances may result in the frequent presence of anatomical variations of the paranasal sinuses in patients with osteoma. METHODOLOGY/PRINCIPAL: The study was performed retrospectively on 2,820 patients subjected to CT examination during 2005 - 2011. Demographic and CT characteristics of osteoma, and associated pathological findings were evaluated for 104 patients with diagnosed osteoma. The presence of anatomical variations was assessed for 51 osteoma patients with a complete medical history, and for 1,233 patients from a control group. RESULTS: The prevalence of osteomas was found to be 3.69%, with male to female ratio 1.08:1. The frontal sinus was most commonly affected. The presence of anatomical variations was more frequent in patients with osteoma than in controls, with significant differences confirmed for the sphenomaxillary plate, infraorbital cell, and crista galli pneumatization. CONCLUSIONS: The paranasal sinus osteoma is associated with higher prevalence of anatomical variations. This can be explained either by the stronger influence of genetic and/or environmental factors on the development of the paranasal sinuses in patients with osteoma, or by their higher susceptibility to above mentioned factors.

Analysis of antibiotic utilization and bacterial resistance changes in a surgical clinic of Clinical Centre, Nis.

WHAT IS KNOWN AND OBJECTIVE: There is little published information about antibiotic utilization and resistance amongst hospital inpatients in Serbia. The purpose of this study was to analyse the variation of antibiotic utilization and the relation between antibiotic utilization and bacterial resistance. METHODS: This analysis was performed in the surgical clinic of one of the biggest Serbian tertiary hospitals, during 2005-2008. Data on the use of antibiotics in surgical inpatients were obtained and expressed as defined daily doses per 100 bed-days. Bacterial resistances were given as percentages of resistant isolates. Following the implementation of a restriction policy in 2005, the prescription of reserve antibiotics was placed under control. RESULTS AND DISCUSSION: During the investigation period the total consumption of antibiotics decreased significantly by 37·8%. Hospital aminoglycoside consumption continued to decrease from 25·1% of the total consumption in 2005 to 5·1% in 2008. During the same period there was a substantial decrease in the use of ceftriaxone (47·8%), ciprofloxacin and metronidazole. Reduction in Escherichia coli resistance to gentamicin correlated significantly with its utilization, while the resistance for all isolates decreased from 58·5% to 44·8%. WHAT IS NEW AND CONCLUSION: This analysis confirms the association between the use of antibiotics and the prevalence of resistance in a surgical clinic. Surveillance of bacterial resistance should be done periodically according to local guidelines for antibiotic therapy of surgical infections, as well as for external comparison.

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride. METHODS: This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times. RESULTS: The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies. CONCLUSIONS/INTERPRETATION: Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin. TRIAL REGISTRATION: ClinicalTrials.gov NCT00331851. FUNDING: The study was funded by Novo Nordisk A/S.

Evaluation of the repaglinide efficiency in comparison to the glimepiride in the type 2 diabetes patients poorly regulated by the metmorfine administration.

OBJECTIVES: An impaired early phase of insulin secretion in the type 2 diabetes mellitus (DM) is very important for the postprandial hyperglycemia. The aim of the study was to compare the efficacy of metformin/repaglinid and metformin/glimepirid regimes in type 2 diabetics uncontrolled with metformin monotherapy. METHODS: Totally, 60 type 2 diabetics with haemoglobin A1c > or = 7.5% and 2000 mg of metformin monotherapy for at least three months were divided in the following groups: A-30 patients with metformin+repaglinid (2 mg for each meal) and B metformin+glimepirid (3 mg in the morning). Assessment of the regimes efficacy comprised of haemoglobin A1c, fasting blood glucose (FBG) and postprandial blood glucose (PBG). Assessment of the safety was performed on the basis of recorded hypoglycemia (<4.0 mmol/l). RESULTS: In both groups, FBG was significantly lower at the end of the study. In the group A it decreased from 9.03 +/- 1.00 to 7.32 +/- 0.65 (p < 0.001), in the group B from 8.94 +/- 1.01 to 7.23 +/- 0.70 (p < 0.001). There was no statistical difference between the groups. PBG was significantly lower after 12 weeks in both groups. CONCLUSION: Metformin/repaglinid is an efficient and safe therapeutic regime in the treatment of the type 2 DM that ensure a better control of PBG levels (Tab. 4, Ref. 18).

Biphasic insulin aspart 30: better glycemic control than with premixed human insulin 30 in obese patients with Type 2 diabetes.

AIM: This 3-month study compared the effect on overall glycemic control of adding biphasic insulin aspart 30 (BIAsp30) and premixed human insulin 30/70 (BHI30) to metformin (met) in insulin-naïve, obese patients (30 males/20 females) with Type 2 diabetes (T2DM). MATERIAL/SUBJECTS: At baseline, patients had a mean age of 58.7 yr, glycated hemoglobin (HbA1c) 9.5%, and body mass index 34+/-2 kg/m2. Patients received either twice-daily BIAsp30 (no.=20) or twice-daily BHI30 (no.=30), and continued to receive maximal doses (2000 mg) of met for the duration of the study, but sulphonylurea oral antidiabetic drugs were discontinued. Primary efficacy endpoint was the change in HbA1c in both groups at study end. Safety endpoints included hypoglycemic episodes and weight gain. RESULTS: Both groups reduced HbA1c by end of trial: BIAsp30 + met by 2.5% [2.16-2.86%; 95% confidence interval (CI)]; BHI30 + met by 1.18% (0.98- 1.39%; 95% CI), giving a significantly better HbA1c reduction with BIAsp30 + met (1.33%; p<0.05). Post-prandial plasma glucose decreased in both groups, by 6.38 mmol/l in patients treated with BIAsp30 + met, and by 4.34 mmol/l in those treated with BHI30 + met (p<0.05). Fasting plasma glucose also decreased in both groups, with a slightly larger decrease seen in BIAsp30 patients than in BHI30 patients (7.36 mmol/l at end of study vs 7.82 mmol/l; p=ns). Subjects treated with BIAsp30 gained less weight than those receiving BHI30 (0.3+/-0.1 kg vs 1.2+/-0.4 kg). There was no significant difference in the frequency or number of hypoglycemic episodes between groups. CONCLUSIONS: Adding BIAsp30 to met in obese patients with T2DM results in better glycemic control and less weight gain than adding BHI30.

Ischaemic colitis--review.

Colonic ischaemia, commonly referred to as ischaemic colitis, is the most common type of intestinal ischaemia. The term "ischaemic colitis" was used by Marston (1966) with three typical patterns of injury described: transient reversible ischaemia, ischaemic ulcers with stricturing, and gangrenous ischaemic colitis. Dominant presenting symptoms were colicky abdominal pain, vomiting, bloody diarrhea, and hematochezia. Patients often have minimal signs on clinical examination. Most patients were diagnosed at colonoscopy. Two regions that are believed to be anatomically vulnerable to ischemic disease are "Griffith's point", at the splenic flexure and "Sudeck's critical point", of the Drummond marginal artery. Clinically, ischaemic colitis is classified as non-gangrenous or gangrenous. Non-gangrenous ischaemic colitis involves the mucosa and submucosa and accounts for 80-85 percent of all cases of ischaemic colitis. Non-gangrenous ischaemic colitis is further subclassified into transient, reversible ischaemic colitis with a less severe form of injury and chronic, non-reversible ischaemic colitis, which includes chronic colitis and stricture and has a more severe form of injury. Gangrenous ischaemic colitis accounts for the remaining 15-20 percent of cases and manifests as the most seve-re form of injury. It includes acute fulminant ischaemia with transmural infarction that may progress to necrosis and death. Specific indications for operation include peritonitis, perforation, recurrent fever or sepsis, clinical deterioration in patients refractory to me-ical management. Relative indications include fulminant colitis, massive hemorrhage, chronic protein losing colopathy, and symptomatic ischemic stricture.

Diagnostic and therapeutic approaches to bleeding from lower parts of the digestive system.

Bleeding from the gastrointestinal tract represents relatively common diagnostic and therapeutic challenge in clinical work of gastroenterologists and surgeons. Bleeding from the lower GI (LGIB) is mostly caused by pathologic conditions of the colon, although the source of bleeding cannot always be exactly localized, thus rendering optimal and prompt therapy difficult. During two year period, at IlI department of the First Surgical Clinic in Belgrade, we performed 424 colonoscopies for LGIB. According to our results the exact diagnosis was established in about 76% (324 patients) showing a great similarity with the results of other published studies (varying between 74% and 89%). The most common causes of bleeding were diverticulosis (37.11%), polyposis (10.3%) and colorectal cancer (46.14%). Besides that we have mentioned some specific facts involving the diagnosis and treatment of LGIB with an accent on some rare conditions, like angiodysplasia. Review of the diagnostic procedures and treatment modalities of the LGIB is useful for everyone who meets with this type of pathology in clinical practice. The diagnostic approach and the surgical treatment of these patients may represent a great problem, since the planning of the operative procedure can be very difficult and with uncertain result. Based on the literary data and our experience we have tried to set the algorithm of the diagnostics and treatment of the LGIB.

Allantoic remnants presenting as a giant retroperitoneal cyst.

Urachal anomalies are usually found in early childhood or just after birth. These usually involve patent ductus urachus, urachal cyst, umbilical-urachal sinus or vesicourachal diverticulum. Very rarely are urachal anomalies found in adults, usully as an infected urachal cyst. We are presenting a case of surgically removed giant urachal retroperitoneal cyst that was found by chance during the abdominal ultrasound examination of a 22 year old man who was initially treated for idiopathic hypertension.

Effect of biphasic insulin aspart on glucose and lipid control in patients with Type 2 diabetes mellitus.

OBJECTIVE: This study examined the efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) monotherapy in insulin-naive patients with Type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: In this 12-week, open-labelled, uncontrolled, clinical-experience study involving 71 patients with secondary oral antidiabetic agent failure, patients received BIAsp 30 after discontinuing oral antidiabetic drugs (OADs). Glucose and lipid concentrations, hypoglycaemic episodes and adverse events were assessed before and after treatment. Patient data were categorised according to previous OADs into the biguanides (BI) plus sulfonylureas/meglitinides (SU/MEG) and SU-only groups. RESULTS: After treatment, glucose and lipid control was significantly improved in both groups, with a greater improvement in the SU-only group. Mean glycated haemoglobin, fasting blood glucose and postprandial blood glucose excursion improved by 2.15 +/- 1.24%, 3.70 +/- 3.18 mmol/l and 1.26 +/- 2.65 mmol/l in the BI plus SU/MEG group, and by 3.09 +/- 1.62%, 6.11 +/- 5.02 mmol/l and 2.06 +/- 2.33 mmol/l in the SU-only group, respectively. Mean high-density lipoprotein cholesterol and triglycerides improved by 0.09 +/- 0.18 mmol/l and 0.94 +/- 1.17 mmol/l in the BI plus SU/MEG group and by 0.09 +/- 0.18 mmol/l and 1.04 +/- 2.72 mmol/l in the SU-only group, respectively. No major hypoglycaemic episodes or serious treatment-related adverse events were reported. CONCLUSIONS: Our study showed that BIAsp 30 treatment safely improved glucose and lipid control in insulin-naive patients with Type 2 diabetes poorly controlled on BI plus SU/MEG and SU-only. Key limitations were the lack of a comparator group and the short study duration.

Salvage rectal surgery--overview.

Recurrence of the disease represents the major problem in patients who undergo "curative" resection for rectal cancer, with published rate ranging from 3 to 50%. Most relapses occur within first two years of follow-up. Depending on the site of the recurrence, it can be local or distant. It also can be solitary or diffuse. In terms of potential surgical cure the best results are achieved with solitary, localized metastases. The most common sites of the solitary metastases are pelvis, liver and lung, with a fairly even distribution among these three sites. Other sites of the localized metastases can be peritoneum, lymph nodes, brain, bone, abdominal wall, ureter and kidney. These sites are less common, but not so amenable to resection. Local recurrence varies depending on the original type of surgery. It can be stated that surgical technique directly influences local recurrence rate in patients with rectal cancer. According to the results from a number of different authors 5-year survival rate after reresection is 2-13% of all patients with locally recurrent cancer, both alone and associated with distant metastases. The most important moment in this problem is to decide when not to operate. The absolute contraindications for salvage surgery are: "frozen pelvis", aneuploid tumors and those with mucinous component, clinical or CT evidence of invasion of the pelvic nerves, lymphatics or veins, or ureter bilaterally. Also, evidence of involvement of the lateral pelvic sidewalls and/or upper sacral marrow, and/or S2 is an absolute contraindication for surgery. Thus, main goals of this type of surgery are respectively: palliation of symptoms, a good quality of life and, if possible, cure with low treatment-related complication rates.

Lymphocyte ecto-5'-nucleotidase in obese type 2 diabetic patients treated with gliclazide.

OBJECTIVE: Lymphocyte 5'-nucleotidase is sensitive to superoxide anion, and is an indicator of oxidative stress in humans. The aim of this study was to assess the effect of the sulfonylurea drugs gliclazide and glibenclamide on lymphocyte ecto-5'-nucleotidase of type 2 diabetic patients. METHODS: Thirty obese type 2 diabetic patients were treated for three months after randomisation either with gliclazide or glibenclamide. Basic laboratory parameters (glycaemia, fructosamine, C-peptide), plasma malondialdehyde levels (MDA) as well as lymphocyte 5'-nucleotidase activity were determined, for all patients and 16 healthy controls, before and after the treatment. RESULTS: 5'-nucleotidase activity in diabetic patients before treatment with gliclazide was 1.61 +/- 0.16 nmol/min/10(6) lymphocytes, and was significantly (P < 0.01) increased compared with the level in healthy controls. After three months of gliclazide treatment, ecto-5'-nucleotidase activity fell significantly by 47.39% and 36% in unstimulated Con A- and PMA-stimulated lymphocytes, respectively. Glibenclamide treatment had no effect on ecto-5'-nucleo-tidase of type 2 diabetic patients. Glycoregulation was improved, as plasma fructosamine decreased from 53.4 to 42.1 and from 50.5 to 43.4 U/g proteins after gliclazide and glibenclamide treatment, respectively. Plasma MDA levels markedly decreased after gliclazide but not glibenclamide treatment. CONCLUSION: These results show that gliclazide treatment inhibits the activity of lymphocyte ecto-5'-nucleotidase and presumably de-creases the concentration of adenosine at the cell surface. A decrease in 5'-nucleotidase activity and attenuation of adenosine production may be a factor in the protection of tissue injury in type 2 diabetic patients.

A physical activity programme and its effects on insulin resistance and oxidative defense in obese male patients with type 2 diabetes mellitus.

AIM: The aim of this study was to investigate the effects of regular aerobic execise on glycaemic control, insulin resistance, cardiovascular risk and oxidative stress-defense parameters in overweight and obese type 2 diabetic patients. METHODS: Changes from baseline to 3 and 6 months of aerobic exercise in total of 30 type 2 diabetics were assessed for physical activity index (PAI), fasting glycaemia (FG), glycated hemoglobin (HbA(1c)), median blood glucose (MBG), insulin resistance (HOMA), triglycerides (TG), cholesterol, the Ashwell Shape Chart Health Risk, SCORE risk, body mass index (BMI), waist and hip circumference, systolic (SBP) and diastolic (DBP) blood pressure, plasma and erythrocyte malondialdehyde (MDA), glutathione, sulphydryl groups and catalase (CAT) and were compared to the results of 30 healthy control subjects. RESULTS: At baseline, significant differences were recorded between the control and diabetes group for FG (P<0.001), HOMA (P<0.001), SBP and DBP (P<0.001), TG (P<0.01), MDA(pl) (P<0.01), CAT (P<0.01) and SCORE risk (P<0.001). Significant changes within the diabetes group were found for PAI (P<0.05), FG (P<0.001), MBG (P<0.05), HbA(1c)(P<0.05), HOMA (P<0.01), SBP and DBP (P<0.001) from baseline to 3 months, as well as for FG (P<0.01), HOMA (P<0.001), SBP and DBP (P<0.05) from 3 to 6 months. Significant (P<0.05) correlations were found for FG and PAI (R=0.432), as well as for HOMA and both HbA(1c)(R=0.412) and SCORE risk (R=-0.387) in the diabetes group. CONCLUSION: Regular aerobic exercise has beneficial effects on glycaemic control, insulin resistance, cardiovascular risk, oxidative stress-defense parameters in overweight and obese type 2 diabetics.

Initiation of sodium spikelets in basal dendrites of neocortical pyramidal neurons.

Cortical information processing relies critically on the processing of electrical signals in pyramidal neurons. Electrical transients mainly arise when excitatory synaptic inputs impinge upon distal dendritic regions. To study the dendritic aspect of synaptic integration one must record electrical signals in distal dendrites. Since thin dendritic branches, such as oblique and basal dendrites, do not support routine glass electrode measurements, we turned our effort towards voltage-sensitive dye recordings. Using the optical imaging approach we found and reported previously that basal dendrites of neocortical pyramidal neurons show an elaborate repertoire of electrical signals, including backpropagating action potentials and glutamate-evoked plateau potentials. Here we report a novel form of electrical signal, qualitatively and quantitatively different from backpropagating action potentials and dendritic plateau potentials. Strong glutamatergic stimulation of an individual basal dendrite is capable of triggering a fast spike, which precedes the dendritic plateau potential. The amplitude of the fast initial spikelet was actually smaller that the amplitude of the backpropagating action potential in the same dendritic segment. Therefore, the fast initial spike was dubbed "spikelet". Both the basal spikelet and plateau potential propagate decrementally towards the cell body, where they are reflected in the somatic whole-cell recordings. The low incidence of basal spikelets in the somatic intracellular recordings and the impact of basal spikelets on soma-axon action potential initiation are discussed.

First thousand rectal cancer cases--local recurrence and survival.

In the period 1990 - 2002, 1674 patients with colorectal carcinoma were operated in the First Surgical Clinic, Third Department for Colorectal Surgery. In 1264 cases (75.5%) rectal carcinoma was the indication for surgical treatment. Sphincter saving procedures (SSP) were performed in 824 (65.2%), abdominoperineal resections (APR) in 340 (26.9%) and resections of rectum with definitive stoma (Hartmann procedure) in 100 (7.9%) patients. We analyzed 1095 cases where curative SSP or APR were performed. All cases where curative resection was not possible because of liver metastases or inability to excise all macroscopic disease were excluded. In the group of patients where SSP was performed (767 cases), there were 26.6% high colorectal anastomoses (8cm from anal verge), 65.4% with low (4-8cm from anal verge) and 8.0% with intersphincteric coloanal anastomosis (cm from anal verge). Patohistological exam showed 5.3% Dukes A, 53.1% Dukes B, 36.5% Dukes C and 4.9% Dukes D. In the APR group (328 cases) there were 1.,5% Dukes A, 32.4% Dukes B, 62.1% Dukes C and 3.5% Dukes D. In this study we analyzed local recurrence and five-year survival in both groups. Recurrence of the disease was registered in 325 (29.6%) out of 1095 patients. Local recurrence was found in 81 (7.,4%) patients. In the SSP group recurrence occured in 215 (28.0%) out of 767 curative resections. Local recurrence alone was found in 53 patients (6.9%). SSP group was also divided into two subgroups; in the first group TME was performed and in second transection of mesorectum was carried out. Analyzing local recurrence in these two groups, in the TME group it was 7.6% and in the transection group 5.6%. In the APR group recurrence was registered in 110 (33.5%) out of 328 patients while local recurrence alone was found in 28 (8.5%) cases. Analyzing mortality we found that 234 (21.4%) out of 1095 patients died during follow-up. In the SSP group 154 out of 767 patients (20.1%) died. In the TME group mortality was 21.7% and in the transection group 16.9%. Mortality in the APR group showed that 80 out of 328 (24.4%) patients died during follow-up. Analysis by the Kaplan-Meier's test shows cumulative survival of 0.69 for all cases. In the SSP group cumulative survival is 0.72 and in the APR group 0.64 with statistically significant difference (p .001). In the TME group cumulative survival is 0.75 and in the transection group 0.,72 with statistically significant difference (p .05). We believe that performing SSP should be encouraged whenever it is possible because there is no difference in local recurrence rates and survival compared to APR. Transection of mesorectum can safely be performed in most cases with tumors located more than 8 cm form anal verge. We believe that exact preoperative staging and preoperative radiotherapy could improve results.

Urinary PC-1 and N-acetyl-beta-D-glucosaminidase activity in patients with type 2 diabetes treated with metformin, gliclazide or glibenclamide.

BACKGROUND: Insulin resistance is a key feature of type 2 diabetes mellitus. Plasma cell differentiation antigen (PC-1) is an inhibitor of insulin receptor tyrosine kinase, and has been implicated in the pathogenesis of insulin resistance. METHODS: Urinary excretion of PC-1 was determined in 45 newly detected, obese diabetic patients treated with metformin (16 patients), gliclazide (14 patients) or glibenclamide (15 patients). Urinary N-acetyl-beta-D-glucosaminidase (NAGA), a lysosomal enzyme, was determined as a marker of tubular damage in diabetes. RESULTS: Basal urinary PC-1 excretion in all three groups of diabetic patients was at the level of healthy controls. Treatment with oral hypoglycaemic drugs did not change significantly the group level or the number of patients in each group with increased PC-1 activity. Urinary excretion of NAGA in patients with type 2 diabetes was not statistically different from the control level. Metformin and gliclazide treatment did not change significantly the group levels of NAGA excretion. However, glibenclamide treatment produced an increased urinary NAGA excretion in the whole group, and in about twice as many patients as in the pre-treatment period.

Urinary PC-1 activity in patients with type 1 diabetes mellitus.

BACKGROUND: Insulin resistance characterizes type 1 diabetes mellitus with nephropathy. The molecular mechanisms of insulin resistance are not completely understood. Recently some advances have been made in identification of transmembrane glycoprotein PC-1 as a potential factor of insulin resistance. METHODS: We measured urinary excretion of PC-1 (alkaline phosphodiesterase I), a potential factor of insulin resistance, and N-acetyl-beta-D-glucosaminidase (NAGA) in 62 type 1 diabetic patients with different damage to the kidney. RESULTS: In newly detected type 1 diabetes patients, before insulin therapy, urine PC-1 excretion was significantly increased (P<0.05) over the control level. However, in patients after 12.4 years of therapy, urinary PC-1 was significantly decreased (P<0.05). Decreased urine PC-1 activity (P<0.05) was found also in type 1 diabetes patients with microalbuminuria and manifest nephropathy, including those with renal failure. Urinary NAGA excretion was found to be significantly increased (P=0.001) in all but the group of type 1 diabetes patients without nephropathy. CONCLUSION: This study of urinary PC-1 in patients with type 1 diabetes shows increased excretion in newly detected patients with poor glycaemic control, but decreased excretion in patients with micro-/macroalbuminuria as well as in those without apparent kidney damage. In patients with primary glomerulonephritis, urinary excretion of PC-1 was significantly decreased and that of NAGA significantly increased compared with the excretion in healthy controls.

Local recurrence and five year survival after abdominoperineal resection of the rectum due to rectal carcinoma.

In the period 01.01.1991-12.31.1996, 523 operations due to rectal carcinoma were performed on the First Surgical Clinic, the Third Department for Colorectal Surgery. Most common localization of tumor was in the distal third of the rectum 65.2%. In the middle third, there were 28.9% and in the upper, intraperitoneal third 5.9%. We performed 286 low anterior stapled resections, 93 anterior resections with hand-sewn anastomosis and 144 Abdominoperineal excisions of rectum (Miles procedure). Pathohistological examination revealed adenocarcinoma in all cases. In this study we analyzed local recurrence and five-year survival after long-term follow-up in the group where Miles procedure was carried out as a potentially curative procedure (except 4.9% cased with Dukes D stage). There were 74.3% males and 23.7% females median age 59.2 years. According to Dukes classification there were 4.9% in stage A, 47.2% in stage B, 43.1% stage C, and 4.9% stage D. There were 4(2.7%) postoperative deaths. Recurrence of the disease was registered in 44 (30.5%) patients. Local recurrence alone was found in 14 (9.7%) patients, while distant spread was registered in 30 (20.8%) patients. At present, the median follow-up is at 72.9 months. Analysis by the Kaplan-Meier's test shows cumulative survival of 61%, and disease free survival of 63.4% at 60 months of the follow-up. Dukes C is associated with a very poor prognosis; survival after 60 months of follow up shows cumulative Survival of 0.35 while Dukes B has far better prognosis (0.86). Analysis of disease free survival by Dukes stage shows that Dukes C has the worst prognosis (disease free survival 0.36 after 60 months), while stage B has much better prognosis (0.84). Local recurrence analysis by the Kaplan-Meier's test shows disease free survival of 84.9% at 60 months of follow-up. Analysis of local recurrence by Dukes stage shows 1.00% disease free survival for cases in stage A, 0.94 for Dukes B and 0.66 for Dukes C, while overall comparison between groups regarding local recurrence using the Wilcoxon (Gehan) statistic shows statistically significant difference (p-0.005). There is no statistical difference between Dukes A and Dukes B cases in distribution of local recurrence.