Urinary volatile Organic compounds in non-alcoholic fatty liver disease (NAFLD), type two diabetes mellitus (T2DM) and NAFLD-T2DM coexistence.

INTRODUCTION: Accumulating evidence have shown a significant correlation between urinary volatile organic compounds (VOCs) profile and the manifestation of several physiological and pathological states, including liver diseases. Previous studies have investigated the urinary metabolic signature as a non-invasive tool for the early discrimination between non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), which nowadays represents one of the most important challenges in this context, feasible only by carrying out liver biopsy. OBJECTIVES: The aim of the study was to investigate the differences in the urinary VOCs profiles of non-alcoholic fatty liver disease (NAFLD) patients, diabetes mellitus (T2DM) subjects and NAFLD/T2DM patients. METHODS: Headspace solid-phase microextraction (HS-SPME) coupled with gas chromatography-mass spectrometry (GC-MS) was applied to profile the urinary VOCs. Urine samples were analysed both under acid and alkaline conditions, to obtain a range of urinary volatiles with different physicochemical properties. RESULTS: Urinary VOCs profiles of 13 NAFLD patients, 13 T2DM subjects and 13 NAFLD/T2DM patients were investigated by multivariate and univariate data analysis techniques which allowed to identify 21 volatiles under alkaline conditions able to describe the NAFLD/T2DM group concerning the other two groups. CONCLUSION: Our results suggest that VOCs signatures can improve the knowledge of the pathological condition where NAFLD coexists with T2DM and discovering new features that are not simply the sum of the two diseases. These preliminary findings may be considered as hypothesis-generating, to be clearly confirmed by larger prospective investigations.

Impaired phagocytic function and increased immune complexes in diabetics with severe microangiopathy.

An increase in circulating immune complexes (AgAb) of medium size has been observed in diabetics with late complications. This increase may be related either to an increased formation or reduced clearance. Alternatively, both mechanisms may be involved. As medium-sized AgAb determined by the C1q solid phase method are mainly removed from circulation by the fixed phagocytes of the reticulo-endothelial system, we investigated the function of these cells using a colloid clearance test in diabetics with various degrees of microangiopathy. Microaggregated iodinated human serum albumin was injected into 30 diabetic volunteers with severe (group 1), moderate (group 2), and absent (group 3) microangiopathy, and into 40 normal volunteers. The colloid clearance was significantly reduced in diabetics with severe microangiopathy in comparison with patients who had no sign of microangiopathy, or with normal subjects. A significant correlation was found between reduced colloid clearance and increased levels of circulating AgAb determined by C1q solid phase method. Results of this study suggest that the increase in circulating AgAb observed in patients with severe microangiopathy may result from an impaired function of mixed phagocytes.

Comparative multicenter study on efficacy and safety of aztreonam and gentamicin in prophylaxis of high-risk colorectal surgery.

The usefulness of antibiotic prophylaxis in reducing the incidence of postoperative infections following colorectal surgery has been defined in many clinical studies. Since a single antibiotic agent covering all the potential pathogens (i.e. Gram-negative aerobes and anaerobes) is not currently available, a combination therapy is usually administered. The present study reports the preliminary results on comparative efficacy and safety of aztreonam and gentamicin (both combined with clindamycin) as short-term prophylaxis in colorectal surgery. Four hundred and fifty-four patients, out of 495 enrolled, were considered evaluable. Incidence of abdominal wound infections was significantly lower in the aztreonam-treated group (5.8% vs 12.5% - p less than or equal to .025). The incidence of perineal wound and abdominal infections, of fever, of need for postoperative antibiotics and the length of postoperative stay were lower in the monobactam group, even if none of these differences were statistically significant. Gram-negative aerobic microorganisms were more often isolated in infected patients from the gentamicin group. Side effects were minor and similar in the two groups. From these preliminary data, the aztreonam-clindamycin combination can be considered a major candidate to replace many of the presently available oral and parenteral regimens.

[Quandrantectomy in the conservative treatment of breast carcinoma]. / La quadrantectomia nel trattamento conservativo del carcinoma della mammella.

Two years after the first evaluation, the authors review the results of quadrantectomy in the conservative treatment of breast carcinoma. Local control of the disease by quadrantectomy with axillary lymphadenectomy and radiotherapy has been more difficult in the T2 patients (4 local relapses out of 41 patients) compared T1 patients (3 local relapses out of 52 patients). Nodal involvement appears to be not crucial for the prognosis (7 patients out of 10 with remote metastases were N- at the time of surgery).

[Surgical treatment of liver trauma: our experience]. / Il trattamento chirurgico dei traumi epatici: nostra esperienza.

The Authors report their ten-year experience in the surgical treatment of liver injuries. Thirty-five patients underwent emergency laparotomy for hepatic trauma: 14 showed associated injuries, mostly of the spleen, while 21 had isolated liver lesions. Emergency surgical operation was performed for those patients with hypovolemic shock due to massive haemoperitoneum, while for all stabilized patients a preoperative ultrasonography or a computerized tomography was diagnostic. With a correct diagnosis, nowadays possible thanks to the overmentioned radiologic means, a group of patients was not treated by laparotomy, but strictly monitorized. For the patients who underwent laparotomy, good results with a low mortality rate were obtained using a surgical conservative treatment.

[Diagnostic findings and the surgical treatment of liver metastases: our experience]. / Orientamenti diagnostici e trattamento chirurgico delle metastasi epatiche: nostra esperienza.

The authors report their 10 year experience of 32 consecutive hepatic resections for metastases. All patients were preoperatively evaluated with US and CT, however, in 9 cases the diagnosis was obtained at laparotomy. In the first years there were no codified criteria for indications to surgery, while recently these were restricted, because of more favourable prognostic evaluations, to the metastases from colorectal carcinoma, endocrine or carcinoid tumours, digestive system neoplasms invading adjacent liver (in this case usually with palliative goal). The low mortality and morbidity registered explain the safety and efficacy of this procedure, also taking into account the fact that currently surgery is the only effective procedure with curative purpose. Criteria for patients selection, particularly in case of colorectal cancer, are referred and discussed and consequently prognostic factors are proposed: hepatic involvement extent, stage of primary tumour, absence of extrahepatic metastases, disease free interval between resection of primary tumour and hepatic resection for metachronous metastases.

[The diagnostic and therapeutic problems of endocrine tumors of the digestive system: our experience]. / Problematiche di diagnosi e terapia dei tumori endocrini dell'apparato digerente: la nostra esperienza.

The authors experience in the surgical treatment of endocrine tumours of the digestive tract is reported. Particularly, they emphasize that in spite of the several syndromes associated with these neoplasms, diagnostic and therapeutic concepts herein analyzed are similar.

Multicenter study of aztreonam in the prophylaxis of colorectal, gynecologic and urologic surgery.

The preliminary results of four multicenter, comparative protocols on the efficacy and safety of aztreonam are discussed. This monobactam antibiotic was used as short-term prophylaxis in patients undergoing colorectal, gynecologic or urologic surgery. When compared with gentamicin in a group of 295 patients undergoing colorectal surgery, aztreonam significantly reduced the incidence of abdominal wound infection (p less than 0.025); it also reduced the incidence of perineal wound and intra-abdominal infections, although these differences were not statistically significant. In patients undergoing abdominal and vaginal hysterectomy, aztreonam was compared with cefotaxime (both combined with clindamycin) in 170 and 142 patients, respectively. No difference in the incidence of infection was found between the two treatment regimens. In the 175 patients undergoing transurethral resection of the prostate, aztreonam was compared with placebo. The prophylactic regimen significantly reduced the number of urinary tract infections (p less than or equal to 0.0001). Its efficacy was particularly evident during the first 10 postoperative days. Side effects experienced by patients taking aztreonam were minor and similar in all three treatment groups studied. Aztreonam (alone or combined with clindamycin) offers a new and efficacious alternative to the standard antibiotic regimens currently used prophylactically in the high-risk postoperative patient.

Aztreonam in the treatment of urinary tract infections: a multicenter trial.

A multicenter trial involving several urologic units in Italy provided pooled data on 1,427 patients with urinary tract infections to evaluate the efficacy and safety of aztreonam, a new monobactam antibiotic. Microbiologic and clinical data were collected methodically in all cases. A majority of the patients (79.9%) were hospitalized during the study period, an associated pathology was noted in 29.1%, and 16.7% were receiving additional therapy. Aztreonam was administered by different routes and in different dosages according to the severity of the pathology. At the end of treatment, 93.6% of the patients showed a positive microbiologic response. Eradication percentages of the 6 main pathogens determined from cultures taken within the seventh day after the end of treatment were as follows: 93.9% for Escherichia coli (n = 415), 86.3% for Pseudomonas sp. (n = 207), 91.6% for Proteus sp. (n = 192), 89.8% for Providencia sp. (n = 59), 96.2% for Klebsiella sp. (n = 56), and 98.1% for Serratia sp. (n = 56). Aztreonam was well tolerated. Of the 1,427 patients evaluated for safety, only 54 (3.8%) reported 55 adverse reactions, necessitating the withdrawal of therapy in 5 (0.2%) instances.

Comparative Multicenter Study on Efficacy and Safety of Aztreonam and Gentamicin in Prophylaxis of High-Risk Colorectal Surgery.

The usefulness of antibiotic prophylaxis in reducing the incidence of postoperative infections following colorectal surgery has been defined in many clinical studies. Since a single antibiotic agent covering all the potential pathogens (i.e. Gram-negative aerobes and anaerobes) is not currently available, a combination therapy is usually administered. The present study reports the preliminary results on comparative efficacy and safety of aztreonam and gentamicin (both combined with clindamycin) as short-term prophylaxis in colorectal surgery. Four hundred and fifty-four patients, out of 495 enrolled, were considered evaluable. Incidence of abdominal wound infections was significantly lower in the aztreonam-treated group (5.8% vs 12.596 - p ≤ .025). The incidence of perineal wound and abdominal infections, of fever, of need for postoperative antibiotics and the length of postoperative stay were lower in the monobactam group, even if none of these differences were statistically significant. Gram-negative aerobic microorganisms were more often isolated in infected patients from the gentamicin group. Side effects were minor and similar in the two groups. From these preliminary data, the aztreonam-clindamycin combination can be considered a major candidate to replace many of the presently available oral and parenteral regimens.

The correlation between insulin antibodies and circulating immune complexes in diabetics with and without microangiopathy.

The relationship between immune complexes and insulin antibodies was evaluated in 237 insulin treated subjects with a duration of diabetes of more than 1 year. Ninety-seven diabetics were selected at random (group 1) whereas 140 according to the presence of diabetic microangiopathy (group 2). Immune complexes were evaluated by the solid phase C1q binding test in all patients and by conglutinin radioimmune assay in most of them. Insulin antibodies were determined by Christiansen's and Anderson's methods. Immune complexes as detected by the solid phase C1q method were found increased in group 1 and there was an inverse correlation between these complexes and insulin antibody levels. In group 2 patients with microangiopathy the amount of this kind of complex was significantly greater than in those without microvascular lesions and there was no correlation with insulin antibodies. Immune complexes as detected by conglutinin were found increased in group 2 patients and these were significantly correlated with the level of insulin antibodies. No increase in these immune complexes was found in patients with microangiopathy when compared with patients without microangiopathy. Insulin antibodies were not correlated with the presence of complications. Overall, immune complexes detected by C1q binding were significantly correlated with the presence of microangiopathy. In patients with high insulin antibody levels the complexes formed were not detected by C1q binding. The immune complexes detected by conglutinin are correlated with insulin antibodies, but not with the presence of microangiopathy.

Aspects of humoral immunity in a prospective study of Type I (insulin-dependent) diabetic subjects treated with insulins of different purity.

In 41 Type 1 (insulin-dependent) diabetic patients, islet cell antibodies, anti-insulin antibodies, and immune complexes measured by two different methods (the C1q solid phase assay and the conglutinin binding test) were studied at diagnosis, and the influence of treatment with insulins of different purity was investigated during the first year of treatment. Twenty subjects were treated with conventional insulins (group 1) while 21 were treated with monocomponent porcine insulins (group 2). The prevalence of islet cell antibodies significantly decreased during the 12-month study period in the 41 patients. From the first month anti-insulin antibodies were always significantly higher in group 1 than in group 2. At diagnosis the prevalence of both types of immune complexes in the 41 patients was higher than in normal subjects. The immune complexes measured by the C1q solid phase method showed a significant and progressive reduction during the follow-up period, whereas the immune complexes assayed by conglutinin showed no significant variation in the same period. The presence of C1q immune complexes was found to correlate with the occurrence of islet cell antibodies both at diagnosis and during the follow-up period. The presence of conglutinin immune complexes, on the other hand, tended to parallel the increase of anti-insulin antibody levels.

Circulating immune complexes in diabetics with severe microangiopathy: evaluation by two different methods.

An investigation on circulating immune complexes (AgAb) was carried out in 80 diabetics with severe microangiopathy and in 71 diabetics without microvascular lesions. The duration of the disease, the type of diabetes, the type of treatment and the main localization of microangiopathy (retinopathy and nephropathy) were taken into account. AgAb were detected by two different methods: the solid phase Clq binding test (ClqSP) and the conglutinin binding test (KgBt). AgAb detected by ClqSP were increased both in prevalence and quantities in diabetics with severe microangiopathy regardless of the duration of the disease and the type of diabetes. Long standing diabetics without microangiopathy had similar prevalence of AgAb as normal controls. The presence of AGAb was not in correlation with the type of treatment and was similar in diabetics with retinopathy and in those with nephropathy. When AgAb were detected by KgBt, they were found with higher prevalence in diabetics than in normal controls but no correlation with microangiopathy was observed. AgAb, detected by KgBt, were higher in long standing type I diabetics. Since the two methods detect different AgAb it is concluded that AgAb present in diabetics seem to be heterogenous and part of them are related to the presence of microangiopathy.

Histology of the islets of Langerhans following administration of human lymphocytes into athymic mice.

Lymphocytes from seven newly diagnosed insulin-dependent (Type 1) diabetics, five islet cell antibody positive unaffected children and five normal subjects were injected i.p. into athymic nude mice. A further six mice were injected with medium and six control mice received no injection. Blood was taken from the tail vein before injection for glucose determination. After 10 days blood was again obtained from the tail vein; the pancreas was removed under deep ether anaesthesia and the mice sacrificed by exsanguination. Routine histological sections of the pancreas were prepared. There was no difference between groups in respect of the initial blood glucose. However, final blood glucose levels were raised in all mice that had received an injection including medium only, the rise being statistically significant both after injection of lymphocytes from normal subjects (P less than 0.05) and from newly diagnosed diabetics (P less than 0.001). Histology did not reveal any evidence of 'insulitis' or islet cell damage although enlarged, hyperplastic islets could be found in each group of treated mice. We conclude that passive transfer of diabetes was not achieved in this animal model. Elevation of blood glucose levels and islet hyperplasia may simply reflect a non-specific 'stress' reaction.

Multicenter trial of prophylaxis with clindamycin plus aztreonam or cefotaxime in gynecologic surgery.

A prospective, randomized, multicenter study was conducted on the efficacy and safety of two prophylactic antibiotic regimens in both abdominal and vaginal hysterectomy. Patients received three intravenous doses of clindamycin (900 mg) plus either aztreonam (1 g) or cefotaxime (1 g); the doses were given at the induction of anesthesia and 8 and 16 hours later. A total of 170 patients undergoing abdominal hysterectomy and 142 patients undergoing vaginal hysterectomy completed the trial and were evaluated. Following abdominal hysterectomy infections occurred at the operative site in 1.2% of patients given a regimen including aztreonam and in 4.7% of those given a regimen including cefotaxime; the difference between the two groups was not significant. Neither were significant differences observed in the incidence of fever, the incidence of bacteriuria, the need for postoperative antibiotics, or the duration of postoperative hospitalization, although results were slightly better for patients receiving clindamycin plus aztreonam. Following vaginal hysterectomy, slightly but not significantly better results for the same parameters were obtained in the group given clindamycin plus cefotaxime. Diarrhea was the only adverse reaction attributable to antibiotic treatment and occurred more frequently in patients given cefotaxime. It was concluded that the two regimens were similarly effective and safe in preventing infections following hysterectomy.

Aztreonam monotherapy as prophylaxis in transurethral resection of the prostate: a multicenter study.

The efficacy and safety of aztreonam in the prophylaxis of urinary tract infection following transurethral resection of the prostate (TURP) in patients with preoperatively sterile urine were studied in a multicenter trial including 300 patients at six Italian urology centers. The present report describes the first 192 patients enrolled in the protocol. Aztreonam or placebo was administered to each patient in three doses, which were given at the induction of anesthesia and 8 and 16 hours later. The development of bacteriuria was monitored by cultures of urine obtained before surgery, 3 days later, at removal of the bladder catheter, at discharge from the hospital, and at a follow-up visit 39-46 days after surgery. A febrile peak was observed for 6% of aztreonam-treated patients and for 20.9% of the placebo group (P less than .005), while bacteriuria was reported in 17.9% and 59.3% of these groups, respectively (P less than .001). From our data, TURP appears to be a clean-contaminated procedure requiring antibiotic prophylaxis, and aztreonam appears to reduce significantly the incidence of postoperative bacteriuria after this surgical procedure.

Circulating immune complexes in diabetics: the influence of sex, age, duration of disease and type of treatment.

The influence of sex, age, duration of diabetes and type of antidiabetic treatment on soluble immune complexes levels was investigated in the sera of 276 randomly selected diabetics. Immune complexes were detected by the solid phase C1q binding test. The prevalence of immune complexes was significantly higher in insulin treated than in non-insulin treated diabetics. Within the insulin treated group, the prevalence in diabetics of 11-20 yr duration was significantly higher than in the remainder. No difference in immune complexes levels was found between males and females. The age of the patients did not have any correlation with the levels of immune complexes. These findings suggest that some of the immune complexes detected in randomly selected diabetics are related to insulin treatment, reflecting either differences in the type of diabetes or the effects of heterologous insulin.

Multicenter comparative study of aztreonam and gentamicin in the treatment of renal and urinary tract infections.

A multicenter comparative study was carried out to evaluate the efficacy of aztreonam and gentamicin in 186 patients with symptomatic renal or urinary tract infections. Patients were divided randomly into two groups: 94 patients received aztreonam 1 g/day intramuscularly and 92 patients received gentamicin 80 mg i.m. twice daily. The clinical and microbiologic results found a single daily dose of aztreonam to be more effective than gentamicin b.i.d. Furthermore, no evidence of side effects was seen with aztreonam. Such results are generally thought to ensure better compliance in outpatients.