A new model of nephrolithiasis involving tubular dysfunction/injury

To better understand the pathogenesis of nephrolithiasis, we developed a new animal model that closely mimics human calcium oxalate stone disease. Rats were treated with a regimen that combines moderate hyperoxaluria (produced by 10 days of feeding with 3% ammonium oxalate) with mild proximal tubular injury/dysfunction (produced by 8 daily injections of gentamicin sulfate -40 mg./kg.). This combined treatment caused a marked increase in the incidence of calcium oxalate crystals and stones over that seen in animals treated with oxalate or gentamicin alone. Using a semiquantitative scoring system for estimating the abundance of crystals in coronal sections of kidneys, we found that 63% of animals receiving gentamicin plus oxalate showed "moderate" numbers of crystal, as compared to 8% of animals receiving oxalate alone; and the majority of the crystals occurred in the papilla, a pattern similar to that seen in human stone disease. Untreated rats and rats treated with gentamicin alone did not exhibit calcium oxalate crystals or stones. Despite the abundance of crystals and stones, animals receiving gentamicin plus oxalate retained relatively normal renal function as judged by creatinine clearance. Thus, the model has several advantages over preexisting models of nephrolithiasis. Crystal and stone deposition develop rapidly (within 14 days). The pattern of deposition resembles that seen in human stone disease and renal function remains relatively normal. These findings indicate that this model of nephrolithiasis may prove useful for studies of the pathogenesis of stone disease. Moreover, they suggest that renal tubular injury and/or dysfunction may produce conditions conducive to the formation and growth of calcium oxalate stones.     

Ceftazidime compared with gentamicin and carbenicillin in patients with cystic fibrosis, pulmonary pseudomonas infection, and an exacerbation of respiratory symptoms. British Thoracic Society Research Committee.

An open randomised comparison of a new intravenous cephalosporin, ceftazidime, with the established regimen of gentamicin and carbenicillin was carried out in patients with cystic fibrosis who had persisting pulmonary infection with Pseudomonas species and who developed acute exacerbations of respiratory symptoms. Fifty patients received ceftazidime and 32 gentamicin and carbenicillin. The ceftazidime and gentamicin were given every eight hours and the carbenicillin every six hours. The mean total daily doses were 151 mg/kg for ceftazidime, 6.3 mg/kg for gentamicin and 450 mg/kg for carbenicillin. The mean duration of treatment was 10 days in patients receiving gentamicin and carbenicillin and 12 days in those receiving ceftazidime. Of the patients with pseudomonas in the initial sputum specimen in whom sputum was cultured after treatment, six (26%) of 23 receiving gentamicin and carbenicillin and seven (18%) of 39 receiving ceftazidime had sputum free from pseudomonas at the end of treatment, but recolonisation occurred subsequently. In those receiving ceftazidime all 10 coexisting organisms were eliminated, whereas only four of seven coexisting organisms in patients receiving gentamicin and carbenicillin were eliminated. Overall clinical improvement occurred in 25 (78%) of 32 patients treated with gentamicin and carbenicillin and 48 (96%) of 50 patients treated with ceftazidime. Nineteen (59%) of the patients receiving gentamicin and carbenicillin but only 15 (30%) of those receiving ceftazidime required admission to hospital or intravenous antibiotics, or both, or died during the three months after treatment. Side effects in both groups were similar, mild, and infrequent. Thrombophlebitis occurred in four patients treated with gentamicin and carbenicillin but in no patients treated with ceftazidime.     

Cardiac allograft survival in rhesus primates treated with combined total lymphoid irradiation and rabbit antithymocyte globulin.

Eighteen abdominal heterotopic cardiac allografts were performed in outbred rhesus primates. For immunosuppression seven animals received six 100-rad/day total lymphoid irradiation (TLI) doses the week preceding transplant and three 3-mg/kg i.m. rabbit antithymocyte globulin (RATG) doses on postoperative days -1, 0, and +1; five animals were given this RATG dose but no irradiation; three were given TLI alone; and three were given no immunosuppressive therapy. Circulating T lymphocyte counts were monitored in all animals (rosettes). Graft survival in the combined TLI-RATG therapy group (169 +/- 15 days) was significantly greater than in untreated (11 +/- 1 days), RATG alone (22 +/- 12 days), or TLI alone (38 +/- 6 days) treated animals (P less than 0.001, 0.0001, and 0.001, respectively). The animals receiving combined TLI-RATG therapy also achieved significantly greater and more prolonged T lymphopenia than that obtained in the other three groups. Six of seven cardiac allografts placed in animals receiving TLI-RATG therapy were removed electively before cessation of electrical activity; however, in four of these rejection pathology was noted. Thus, it seems that combined TLI-RATG therapy may be of benefit in the management of transplant recipients, but its use will probably not abolish these patients' requirements for immunosuppressive maintenance measures.     

Synergistic effect of nonspecific immunostimulation and antibiotics in experimental peritonitis

To assess the role of combined immunomodulator and antibiotic therapy in sepsis, glucan--a beta 1,3 polyglucose--and gentamicin were administered in a model of murine peritonitis. ICR/HSD mice received one of four treatment regimens: 5% dextrose; gentamicin 0.02 mg intramuscularly (sub-MIC) 2 hours before peritonitis; glucan 0.1 mg intraperitoneally 24 hours before peritonitis; combined glucan-gentamicin treatment. All animals were challenged with 1 X 10(8) Escherichia coli intraperitoneally. Long-term survival was significantly enhanced in the combined therapy group (56%, p less than 0.05) when compared with D5W (0%), gentamicin alone (0%), or glucan alone (9%). Macrophage secretory activity, as assayed by interleukin-1 (IL-1) production, was significantly enhanced by combined therapy when compared with the other three treatment groups. Combined therapy significantly reduced E. coli bacteremia at 8 hours after inoculation, when compared with the other three groups. Availability of host neutrophils was assessed by peripheral counts and bone marrow proliferation assay. Combined glucan-gentamicin significantly enhanced bone marrow proliferation when compared with the other three groups and this enhancement correlated with increased circulating neutrophils. Combined immunomodulator and antibiotic therapy had synergistic effects on survival in E. coli peritonitis. This combined therapy enhanced macrophage secretory activity and bone marrow proliferation. Clinical use of immunomodulators may alter conventional use and dosage of antibiotics.     

The combined effect of cyclosporine a and gentamicin on enzymuria in the Sprague-Dawley rat

Male Sprague-Dawley rats (8 per group) were administered a single oral dose of cyclosporine A (10, 30 and 50 mg/day) for 5 days or vehicle (corn oil, 1.5 mL/kg) and urinary enzymes excretion was monitored. Only minor changes in enzymuria were observed in the 10 and 30 mg/kg group. However, in the 50 mg/kg group, nephrotoxicity was evident by significant increase in the excretion of N-acetyl-beta-D-glucosaminidase (NAG), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH on day 2 of treatment. As chemotherapeutic drug interaction with cyclosporine A (CyA) is thought to aggravate its nephrotoxicity, the effect of combined CyA (30 mg/kg) and the antibiotic gentamicin (50 mg/kg) for 5 days was investigated. Gentamicin alone caused a significant enzymuria, whilst co-treatment of rats with CyA gave rise to increased changes in enzymuria on days 1 and 2, between the groups receiving gentamicin+vehicle and those receiving CyA+gentamicin. This was particularly marked by significant changes in LDH excretion. In contrast these observed differences were not paralleled by changes in serum creatinine and other functional parameters. Treatment with gentamicin, appears to enhance CyA nephrotoxicity, but only in the first 2 days, after this there was no significant differences between the two groups. Our data suggest that urinary enzyme measurements could serve as a valuable non-invasive means of monitoring renal performance in animals or humans who may be exposed to combination of drugs. CyA is found not to potentiate the nephrotoxic effect of gentamicin in the animal model used in this study. It therefore appears safe to use the combined therapy particularly in the treatment of transplant patients.     

Therapy of symptomatic pyelonephritis in women

A prospective randomized controlled study was performed on 44 women with community-acquired, uncomplicated pyelonephritis requiring hospitalization. The study was designed to determine if an extended course of therapy (21 days) would be more effective than the conventional 10-day course of therapy. All patients initially received either gentamicin or tobramycin parenterally for 48 to 72 hours, and then were prescribed an oral agent that possessed in vitro inhibitory activity for the urinary pathogen to complete the course of therapy. Duration of medication was assigned according to a table of random digits. Of the 22 women receiving the 10-day treatment 17 were cured, 4 experienced a reinfection and none had a relapse, compared to 12, 5 and 3, respectively, of 22 receiving the 21-day treatment. Analysis of the therapeutic failures did not demonstrate any superior response for either treatment program (p less than 0.75 and greater than 0.50). No statistically increased incidence of adverse drug reactions occurred in patients receiving the extended course of therapy. Our data do not support an extended course of therapy in women with acute symptomatic pyelonephritis uncomplicated by structural abnormalities.     

THE COMBINED EFFECT OF CYCLOSPORINE A AND GENTAMICIN ON ENZYMURIA IN THE SPRAGUE-DAWLEY RAT

Male Sprague-Dawley rats (8 per group) were administered a single oral dose of cyclosporine A (10, 30 and 50 mg/day) for 5 days or vehicle (corn oil, 1.5 mL/kg) and urinary enzymes excretion was monitored. Only minor changes in enzymuria were observed in the 10 and 30 mg/kg group. However, in the 50 mg/kg group, nephrotoxicity was evident by significant increase in the excretion of N-acetyl-β-D-glucosaminidase (NAG), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH on day 2 of treatment. As chemotherapeutic drug interaction with cyclosporine A (CyA) is thought to aggravate its nephrotoxicity, the effect of combined CyA (30 mg/kg) and the antibiotic gentamicin (50 mg/kg) for 5 days was investigated. Gentamicin alone caused a significant enzymuria, whilst co-treatment of rats with CyA gave rise to increased changes in enzymuria on days 1 and 2, between the groups receiving gentamicin + vehicle and those receiving CyA + gentamicin. This was particularly marked by significant changes in LDH excretion. In contrast these observed differences were not paralleled by changes in serum creatinine and other functional parameters. Treatment with gentamicin, appears to enhance CyA nephrotoxicity, but only in the first 2 days, after this there was no significant differences between the two groups. Our data suggest that urinary enzyme measurements could serve as a valuable non-invasive means of monitoring renal performance in animals or humans who may be exposed to combination of drugs. CyA is found not to potentiate the nephrotoxic effect of gentamicin in the animal model used in this study. It therefore appears safe to use the combined therapy particularly in the treatment of transplant patients.     

Glucan enhances survival in an intraabdominal infection model

The immunomodulator glucan exists in two forms, particulate (glucan-P) and soluble (glucan-F). Both preparations of glucan, either alone or in combination with antibiotic therapy, were evaluated for their ability to augment survival in rats following cecal ligation and puncture (CL/P). Adult male rats were infused once daily for 5 consecutive days with either glucan-P (10 mg/kg), glucan-F (10 mg/kg), or 5% (w/v) dextrose in water. Three days later all rats underwent CL/P. Postoperatively, the rats received (a) no therapy, (b) saline (1 ml subcutaneously every 12 hr) or (c) ampicillin (33 mg/kg subcutaneously every 12 hr) for 7 days. Without any associated pre-or postoperative treatment, CL/P was associated with an 85% 7-day mortality. Neither glucan preparation alone significantly altered this mortality. Administering ampicillin postoperatively decreased the mortality to 53% (P less than 0.001 vs untreated controls). When postoperative ampicillin therapy was combined with preoperative glucan treatment, the mortality was reduced even further (26% for glucan-P, 21% for glucan-F; P less than 0.02 vs ampicillin-treated controls). We conclude from these results that (i) neither glucan preparation alone effectively enhances survival following CL/P when using the doses and administration schedule employed herein, (ii) both glucan-P and glucan-F do act synergistically with antibiotics to enhance survival in this rat model of polymicrobial sepsis, and (iii) in this particular model, nontoxic glucan-F is as efficacious as glucan-P.     

Effect of high-dose ampicillin and cloxacillin on bleeding time and bleeding in open-heart surgery

To determine if platelet dysfunction caused by high doses of penicillin compounds is of practical importance in patients with additional haemostatic defects perioperatively, a study was made of patients undergoing open-heart surgery. They were randomly assigned to prophylactic treatment with ampicillin 8 g plus cloxacillin 4 g daily for three days, or with cephalothin 8 g daily for three days. Fifty patients in each group were evaluated. The median bleeding time preoperatively and on days 1 and 4 postoperatively did not differ between the groups. The bleeding time was prolonged beyond the normal range in eight patients of the ampicillin/cloxacillin group and in three of the cephalothin group (p less than 0.05). Prolonged bleeding time was not associated with lower platelet count or greater blood loss. The total blood loss and the amounts of transfused blood, platelets and cryoprecipitate were all greater in the ampicillin/cloxacillin group, but the difference was not statistically significant. Combined use of ampicillin and cloxacillin in open-heart surgery is associated with increased bleeding, but the increase is without practical importance.     

Acinetobacter peritonitis during chronic peritoneal dialysis

Among gram-negative bacilli isolated during peritonitis in chronic peritoneal dialysis (CPD), Pseudomonas species are most common but Acinetobacter species are nearly as frequent. A survey of more than 450 patient-years' experience with CPD revealed 23 episodes of Acinetobacter peritonitis (AP), making this the second most common form of gram-negative peritonitis. Concomitant break in sterile technique and exit-site/tunnel infection were infrequent. AP appeared as the first peritonitis episode in five cases and as the second in six cases, and the duration of CPD at the time of AP ranged from less than 1 to greater than 56 months. However, AP was noted to appear shortly after treatment of another peritonitis episode or shortly after CPD access placement, within 2 months in 11 cases (47%) and within 3 months in 14 cases (61%). Treatment with intraperitoneal antibiotics succeeded in 21 cases (91%) without CPD interruption or catheter removal, with tobramycin or gentamicin alone in 16 cases, and with combined aminoglycoside and penicillin or cephalosporin in six cases. In two cases intraperitoneal antibiotics alone were insufficient therapy: one case with concomitant tunnel infection and dialysate leak and one case with bacteremia while receiving corticosteroids. The time-dependent incidence of AP suggests opportunistic infection during a vulnerable period in the first 2 to 3 months following another peritonitis episode, but AP also appears amenable to intraperitoneal antibiotic therapy alone without interruption of the CPD routine in the majority of cases.     

Practice guidelines for the treatment of uncomplicated cystitis

The Infectious Diseases Society of America has published guidelines for the treatment of uncomplicated cystitis. Recommendations are that for healthy, adult, nonpregnant women with bacterial cystitis, 3 days of trimethoprim/ sulfamethoxazole (TMP/SMZ) or trimethoprim alone is standard therapy in those regions where less than 10% to 20% of Escherichia coli that cause such infections is resistant to TMP/SMZ. In those regions where resistance is more than 10% to 20%, the committee recommended using an oral fluoroquinolone for 3 days, and that alternatives such as nitrofurantoin for 7 days or fosfomycin as single-dose therapy need more study. These recommendations were established in the late 1990s as resistance to TMP/SMZ among uropathogens was increasing in the United States, a phenomenon earlier observed in other parts of the world. Clinicians should be alert to patients infected with possibly resistant organisms, eg, patients who have recently been hospitalized or are receiving antibiotics.     

Erregerspektrum und Antibiotikaresistenz beim Harnwegsinfekt und Konsequenzen für die Antibiotikatherapie

From 1994 to 2001 all uropathogens of urology inpatients were identified and the sensitivity to 14 antibiotics was tested [trimethoprim (TMP)/sulfamethoxazole (SMZ), ciprofloxacin, ampicillin, mezlocillin, ampicillin/sulbactam, piperacillin/tazobactam, cefuroxime, cefpodoxime, cefotaxime, ceftazidime, gentamicin, penicillin, oxacillin, and vancomycin]. The following results were obtained: 1. No general trend toward an increase in resistance was noted during the observation period except for E. coli resistance to TMP/SMZ (25.1% in 2000) and ciprofloxacin (10.4% in 2000). 2. Vancomycin-intermediary staphylococci or vancomycin-resistant enterococci played no role. 3. The lowest resistance to all pathogens was found for piperacillin/tazobactam (8.4% in 2001); carbapenems were not tested. 4. If uropathogens are stratified into gram-positive and gram-negative bacteria, for oral administration, ciprofloxacin is the antibiotic with the lowest resistance rate for urinary tract infections with gram-negative pathogens and ampicillin/sulbactam for gram-positive pathogens. 5. Subsequent to further differentiation of the pathogens with simple tests that can be performed after overnight incubation of the culture, empirical antibiotic therapy can then be effectively employed. To draw the correct conclusions from these data, the urologist must either be personally involved in the analytical procedure or receive the interim results promptly.     

Increased nephrotoxicity of gentamicin in pyelonephritic rats

Multiple factors may increase the nephrotoxic potential of aminoglycosides. We studied gentamicin susceptibility of kidneys infected with E. coli. Several parameters of renal function, histological changes on light and electron microscopy, and drug levels in renal parenchyma were compared in pyelonephritic and normal rats treated with low doses (10 mg/kg/Q8 hr for 3 days), or high doses (60 mg/kg/day for 14 days), of gentamicin. A significant increase (P less than 0.01) in beta-galactosidase and protein excreted in urine over a period of 17 days associated with severe changes in diuresis and osmolality was noted in the infected treated rats (low doses) compared with normal, treated, infected or control animals. Histological modifications compatible with gentamicin nephrotoxicity were more persistent in the infected treated animals. A significant decrease in 14C inulin (P less than 0.01) and 3H-PAH clearance and secretion (P less than 0.02) was observed in the infected treated rats receiving high doses of antibiotics. Cellular necrosis and tubular desquamation also were more severe in this group. Gentamicin levels in the cortex and medulla of infected animals were significantly higher than in the normals (P less than 0.01) and might have been responsible for the increased toxicity noted in the pyelonephritic animals. Infected kidneys appeared to be more susceptible to the nephrotoxic potential of gentamicin.     

Captopril enhances aminoglycoside nephrotoxicity in potassium-depleted rats

We demonstrated that potassium depletion significantly increased gentamicin nephrotoxicity in Sprague-Dawley rats (100 mg X kg-1 X day-1). To determine whether this enhanced toxicity was mediated by renin secretion, we evaluated the effect of a converting enzyme inhibitor in this model. When we administered the combination of captopril (100 mg X kg-1 X day-1) and gentamicin in potassium-depleted rats, we observed a surprising and significant adverse effect of this combination on the clearances of inulin (CIn) and PAH (CPAH) and renal blood flow (RBF). Pretreatment with indomethacin significantly improved CIn and CPAH, and potassium repletion abolished this effect entirely. In potassium-depleted animals that received both gentamicin and captopril, the intra-arterial administration of imidazole, a thromboxane synthetase inhibitor, significantly reduced urinary TXB2 excretion and significantly improved RBF and CIn in vivo. In the same group of animals, administration of the kallikrein antagonist aprotinin also significantly increased both RBF and CIn. To measure total renal thromboxane B2 production (TXB2), we perfused kidneys ex vivo with cell-free perfusate. Three groups of animals were studied: potassium-repleted control animals, potassium-depleted control animals, and potassium-depleted animals treated with gentamicin alone, captopril alone, or the combination of gentamicin and captopril. We measured TXB2 in renal venous effluent by radioimmunoassay. Ex vivo perfused kidneys from potassium-depleted control animals produced significantly more TXB2 than potassium-repleted controls. Kidneys from potassium-depleted animals that received both gentamicin and captopril produced significantly greater amounts of TXB2 than did kidneys from potassium-depleted animals treated with captopril alone, gentamicin alone, or control potassium-depleted kidneys. The administration of imidazole ex vivo at a rate equivalent to in vivo administration (10 microM/min) reduced TXB2 production by potassium-depleted kidneys that received the combination of gentamicin and captopril to that of potassium-repleted control kidneys. These results suggest that the deleterious effect of captopril in potassium-depleted rats that received gentamicin is due at least in part to kinin-stimulated renal TXB2 production.     

IBUPROFEN COMBINED WITH ANTIBIOTICS SUPPRESSES RENAL SCARRING DUE TO ASCENDING PYELONEPHRITIS IN RATS

PURPOSE: In acute pyelonephritis renal scarring may be decreased by immediate antibiotic therapy. Unfortunately in children there is often a delay in starting treatment, which increases the likelihood of renal scarring. In rodents immediate antibiotic therapy is effective for preventing renal scar formation resulting from experimentally induced pyelonephritis. However, the same treatment beginning 72 hours after infection does not prevent renal scarring in this paradigm. We examined whether delayed administration of the nonsteroidal anti-inflammatory agent ibuprofen only or combined with antibiotics suppresses renal scarring in a model of ascending pyelonephritis in rats. MATERIALS AND METHODS: An inoculum of 5x10(9) organisms per ml. of Escherichia coli strain BH-5 was instilled into the bladder of rats and the urethra was occluded for 4 hours. Groups of animals were and were not treated with 15 mg./kg. cefadroxil or 10 mg./kg. ibuprofen given twice daily for 5 days, or the 2 drugs combined. Treatment began 72 hours after inoculation. In an additional group of rats sterile phosphate buffered saline was instilled into the bladder. In each rat the kidneys were examined grossly and microscopically 6 weeks later. RESULTS: Combined antibiotics and ibuprofen significantly inhibited gross renal scarring compared with no treatment or antibiotics only (p<0.05). No difference in renal scarring was detected in animals that received no treatment versus those that received antibiotics or ibuprofen only (p>0.05). CONCLUSIONS: Renal scarring resulting from acute pyelonephritis in this rat model is not decreased by delayed treatment with antibiotics only. The addition of ibuprofen to antibiotic therapy is effective for decreasing renal scarring due to acute pyelonephritis even when treatment is delayed for 72 hours.     

ESWL as the treatment for lithiasis in horseshoe kidney.

Thirteen patients with lithiasis and horseshoe kidney were evaluated (4 cases with bilateral stones). Fifteen kidney units were treated with extracorporeal shock wave lithotripsy (ESWL), and in 2 cases, percutaneous nephrolithotomy (PCN) was used. The excellent results achieved with ESWL (80%) and the low incidence of complications (2 cases of nephritic colics and 1 case of acute pyelonephritis), lead us to propose ESWL as the therapy of choice for lithiasis in patients with horseshoe kidneys. PCN alone or in association with ESWL would be used in cases with large lithiasic masses. Conventional surgery would only be indicated in those cases which due to their high degree of complexity or difficult endourological access prevent the use of the above-mentioned techniques.     

Treatment of mice with sepsis following irradiation and trauma with antibiotics and synthetic trehalose dicorynomycolate (S-TDCM)

Compromise of antimicrobial defenses by irradiation can result in sepsis and death. Additional trauma can further predispose patients to infection and thus increase mortality. We recently showed that injection of synthetic trehalose dicorynomycolate (S-TDCM) significantly augments resistance to infection and increases survival of mice compromised either by whole-body irradiation with gamma radiation or equal mixtures of fission neutron and gamma radiation. In this study, C3H/HeN mice were given a lethal dose of gamma radiation (8.0 Gy) and an open wound (15% total body surface area [TBSA]) 1 hr later while anesthetized. Irradiated/wounded mice became more severely leukopenic and thrombocytopenic than mice exposed to radiation alone, and died from natural wound infection and sepsis within 7 days. S-TDCM given 1 hr postirradiation increased survival of mice exposed to radiation alone. However, this treatment did not increase survival of the irradiated/wounded mice. Systemic antibiotic therapy with gentamicin or ofloxacin for 10 days significantly increased survival time compared with untreated irradiated/wounded mice (p less than 0.01). Combination therapy with topical gentamicin cream and systemic oxacillin increased survival from 0% to 100%. Treatment with S-TDCM combined with the suboptimal treatment of topical and systemic gentamicin increased survival compared with antibiotic treatment alone. These studies demonstrate that post-trauma therapy with S-TDCM and antibiotics augments resistance to infection in immunocompromised mice. The data suggest that therapies which combine stimulation of nonspecific host defense mechanisms with antibiotics may increase survival of irradiated patients inflicted with accidental or surgical trauma.     

Perioperative management of patients undergoing elective colorectal surgery in Israel: a national survey

BACKGROUND: The approach to perioperative antibiotic prophylaxis, bowel preparation, and postoperative routines in elective colorectal resections has changed over the last two decades. The aim of this national survey was to document the current methods of perioperative management of those patients scheduled for elective colorectal resections in surgical departments in Israel. METHODS: A mail and telephone survey of surgical departments was conducted in 2001 in order to evaluate the routines of perioperative management of elective colorectal resections. Re-evaluation was performed in 2004. RESULTS: In 2001, all but one of the responders used low-residue diet preoperatively and combined oral and parenteral antibiotic prophylaxis. Polyethylene glycol or sodium phosphate bowel preparation was used by 69% of the responders. The most common oral regimens were a combination of neomycin plus metronidazole (43.5%) or neomycin plus erythromycin (47.8%). The most common parenteral regimens used were gentamicin plus metronidazole or gentamicin plus metronidazole plus ampicillin (56.5% and 17% of the responders, respectively). Cephalosporins alone or in combination were used in three departments. In 17 departments (74%), parenteral prophylactic antibiotics were continued for 24 h or longer (up to 72 h). All but one of the departments left a nasogastric tube for 1-5 days after surgery. There were substantial changes over the last three years-that is, less use of preoperative restriction diets, shorter duration of perioperative antibiotic coverage, more common use of cephalosporins, switch to sodium dihydrogen and sodium hydrogen phosphate bowel preparation, shorter use of postoperative nasogastric drainage, and faster resumption of peroral fluids. CONCLUSIONS: In 2001, the majority of surgical departments in Israel used a conservative approach to perioperative management of patients undergoing elective colorectal resections. Significant changes occurred during the last three years. The perioperative routines used today in most general surgery departments in Israel comply with current recommendations.     

Randomized trial of adjuvant therapy for "high risk" primary malignant melanoma

Retrospective pathological classification of 213 patients with malignant melanoma identified a group at high risk of recurrence (25% developed recurrence in 12 months, 50% by 5 years) after resection for apparent cure. Using these criteria, 70 patients were identified after resection of all apparent disease as being at high risk for recurrent melanoma. They were randomly assigned to one of the three adjuvant treatment arms: chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC), immunotherapy with bacillus Calmette-Guerin (BCG), or combined chemoimmunotherapy. Six of 20 patients receiving DTIC developed recurrence (30%) and four died (20%). Five of 28 patients receiving BCG developed recurrence (18%) and two died (7.5%). There have been no recurrences or deaths in 22 patients receiving combined chemoimmunotherapy. In the prevention of early recurrence, the combined therapy arm was significantly superior to both the immunotherapy arm (p less than 0.05) and the chemotherapy arm (p less than 0.01). In terms of survival, combined therapy also was superior to chemotherapy alone (p less than 0.05).     

Effect of heparin and heparin fractions on experimental abscess formation

To evaluate the effectiveness of heparin and heparin fractions in decreasing abscess formation, rats were divided into six groups. A fibrin clot containing 10(9) live Escherichia coli was placed in the peritoneal cavity of each rat. Group 1 (controls) received daily subcutaneous (SQ) injections of 0.1 mL of saline solution. Group 2 received daily intramuscular injections of gentamicin, 12.5 mg/kg. Group 3 received a daily SQ dose of 30 U of porcine heparin. In addition to gentamicin, group 4 received heparin, group 5 received heparin fraction PK10169, and group 6 received heparin fraction CY216, all in daily SQ doses of 30 U. Survivors were killed at ten days and examined for intra-abdominal abscesses. All group 1 animals developed abscesses. Abscess formation was significantly decreased in all groups receiving gentamicin. When used with gentamicin, neither heparin nor heparin fractions decreased the number of abscesses formed when compared with gentamicin alone. Heparin or heparin fractions in combination with gentamicin did decrease abscess size significantly when compared with controls.