Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.

Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation.

Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.

Prevalence of deep vein thrombosis and pulmonary embolism in superficial thrombophlebitis of the lower limbs: prospective study of 60 cases.

AIM: Superficial thrombophlebitis (ST) ascending the lower limbs is a common disease, which may be associated with deep vein thrombosis (DVT) and pulmonary embolism (PE). The aim of this study was to investigate the prevalence of DVT and PE as complications of ascending ST of the lower limbs in the great saphenous vein (GSV) or SSV (SSV) and probable risk factors. METHODS: For this study 60 consecutive patients were enrolled with ascending ST of the GSV or SSV, seen between 2000 and 2003 at a public hospital in Botucatu, SP, Brazil. All patients were assessed clinically, by venous Duplex scanning of the lower limbs to confirm ST and test for DVT, and by means of pulmonary scintigraphy to test for PE. RESULTS: In 13 ST cases (21.67%) there was concomitant DVT and 17 ST patients (28.33%) also had PE. Eleven patients had a clinical status suggestive of DVT, but only in eight of these (61.5%), this clinical diagnosis was confirmed. Fourteen patients had a clinical status suggestive of PE, and this diagnosis was confirmed in six cases (35.30%). ST patients who also had DVT and/or PE were given anticoagulant treatment with heparin and warfarin. None of the variables studied was predictive of DVT or PE (P>0.05). However, the presence of varicose veins reduced the risk of patients having DVT (relative risk=9.09; 95%CI:1.75 - 50.00 and P=0.023). CONCLUSIONS: The prevalence rates of PE (28.3%) and DVT (21.6%) were elevated in this sample of ascending ST cases, indicating a need for detailed assessment of patients for signs of these complications, including for therapeutic management decision making.

Drinking water quality: an in vitro approach for the assessment of cytotoxic and genotoxic load in water sampled along distribution system.

An in vitro approach was performed to assess the quality of drinking water collected at two treatment/distribution networks located near the source (Plant #1) and the mouth of River Po (Plant #2). The water was sampled at different points of each distribution network, before (raw water) and after the chlorine dioxide disinfection, and in two points of the pipeline system to evaluate the influence of the distribution system on the amount and quality of the disinfection by-product. Cytotoxicity and genotoxicity of water extracts were evaluated in human peripheral lymphocytes and Hep-G2 cells by the use of the micronucleus (MN) test and Comet assay. Raw water samples of both plants induced cytotoxic effects, but not the increases of MN frequency in Hep-G2 cells and in human lymphocytes. Increases of DNA damage in human leukocytes was detected by Comet assay for raw water of Plant #2 at concentration > or = 0.25 Leq/mL. The disinfection process generally has reduced the toxicity of water samples, even if potential direct DNA-damaging compounds have been detectable in drinking water samples. The proposal approach, if currently used together with chemical analysis, can contribute to improve the monitoring drinking water.

Glutaraldehyde-treated homologous vein graft as a vein substitute: experimental study in rabbits.

AIM: Vein reconstruction using grafts may prevent sequelae of venous interruption or lesion. Autologous vein is sometimes unsuitable or absent for a vascular restoration. The aim of this study was to study glutaraldehyde-treated homologous vein graft as vein substitute and compare it with autologous vein as a substitute for a vena cava segment in rabbits. METHODS: Sixty rabbits were allocated into two groups: autologous vein graft (AG), and glutaraldehyde-treated homologous vein graft (HG). Each group was subdivided into three subgroups (N.=10) to be studied at: 24 hours, 14 days, and 28 days. The veins were treated in 0.19% glutaraldehyde, pH=7.4, for 1 hour and kept at 4 degrees C in saline with added gentamicin and amphotericin B. The animals received benzanthine penicillin on the day of graft implantation and heparin only during surgery. The grafts were implanted into the vena cava. Anastomosis was performed with interrupted sutures. Cavography was performed, after surgery, and at the time the animals were killed. Evaluation of the veins was made macroscopically and by light and scanning electron microscopy. RESULTS: Fibrosis was seen around the grafts at 14 and 28 days, with no difference in intensity between the groups. Cavography performed before euthanasia of the animals showed 4 partial thrombi in AG (2 at 24 hours and 2 at 14 days), 3 in HG (2 at 24 hours and 1 on day 14), and 4 occlusive thombi in HG (3 at 14 days and 1 at 28 days). Macroscopic examination did not show any thrombus in AG. In HG, two partial thrombi were confirmed at 24 hours and three occlusive thrombi at 14 days. There was no statistical difference in relation to patency between the two groups. At 14 and 28 days, the histological sections showed intimal hyperplasia of similar intensity and variable distribution in both groups. Evaluation by electron microscopy showed at 24 hours lesion areas characterized by absence of the endothelium on the graft surface, presence of inflammatory cells, and, at some sites, presence of mural thrombi in AG and HG. Both groups at 14 and 28 days showed endothelial cells covering the lesion area on the graft surface, this covering being larger in AG than in HG. CONCLUSIONS: In the studied model, both grafts behaved similarly in relation to patency and morphological characteristics. This suggests that the glutaraldehyde-treated graft can be a promising alternative for vein reconstruction, justifying further animal studies with the aim of using it in human surgery.

Advances in ultrasound techniques improve early detection of deep vein thrombosis.

AIM: This study aimed at assessing the accuracy of ultrasound (US) in the diagnosis of recent deep vein thrombosis (DVT) in an experimental study in dogs. DESIGN: blinded and randomized experimental study. Twenty dogs were randomly divided in two groups: control group (CG) and thrombosis group (TG). US was performed in the pre- and postoperative period. Phlebography was performed immediately prior to the postoperative US. After the second US, a surgery was performed to detect whether thrombus was present or not. US results were compared to those of phlebography and surgical findings. RESULTS: In all dogs, inferior vena cava (IVC) was compressible. The relations of IVC diameter with the aorta were higher (P<0.005) in TG than in CG. Spectral Doppler in spontaneous breathing, tissue harmonic imaging, power Doppler and B flow showed sensitivity, specificity and accuracy of 1. Phlebography presented sensitivity of 90%, specificity of 80% and accuracy of 85%, when compared to surgical finding. CONCLUSIONS: For the diagnosis of recent DVT in the experimental model used, venous compressibility proved to be inefficient. The ratio of IVC diameter to aorta, when increased, suggests thrombosis. The use of new US technological advances increases accuracy. Phlebography was less accurate than US.

Incorrect use of thromboprophylaxis for venous thromboembolism in medical and surgical patients: results of a multicentric, observational and cross-sectional study in Brazil.

OBJECTIVES: Although effective strategies for the prevention of venous thromboembolism (VTE) are widely available, a significant number of patients still develop VTE because appropriate thromboprophylaxis is not correctly prescribed. We conducted this study to estimate the risk profile for VTE and the employment of adequate thromboprophylaxis procedures in patients admitted to hospitals in the state of São Paulo, Brazil. METHODS: Four hospitals were included in this study. Data on risk factors for VTE and prescription of pharmacological and non-pharmacological thromboprophylaxis were collected from 1454 randomly chosen patients (589 surgical and 865 clinical). Case report forms were filled according to medical and nursing records. Physicians were unaware of the survey. Three risk assessment models were used: American College of Chest Physicians (ACCP) Guidelines, Caprini score, and the International Union of Angiololy Consensus Statement (IUAS). The ACCP score classifies VTE risk in surgical patients and the others classify VTE risk in surgical and clinical patients. Contingency tables were built presenting the joined distribution of the risk score and the prescription of any pharmacological and non-pharmacological thromboprophylaxis (yes or no). RESULTS: According to the Caprini score, 29% of the patients with the highest risk for VTE were not prescribed any thromboprophylaxis. Considering the patients under moderate, high or highest risk who should be receiving prophylaxis, 37% and 29% were not prescribed thromboprophylaxis according to ACCP (surgical patients) and IUAS risk scores, respectively. In contrast, 27% and 42% of the patients at low risk of VTE, according to Caprini and IUAS scores, respectively, had thromboprophylaxis prescribed. CONCLUSION: Despite the existence of several guidelines, this study demonstrates that adequate thromboprophylaxis is not correctly prescribed: high-risk patients are under-treated and low-risk patients are over-treated. This condition must be changed to insure that patients receive adequate treatment for the prevention of thromboembolism.

Long-term histopathologic evaluation of inferior vena cava after modified Greenfield filter implantation. Experimental study in sheep.

AIM: The authors assess a modified Greenfield filter (GF) for the long-term patency, filter tilting and histopathologic alterations of the inferior vena cava (IVC). METHODS: Adult sheep (n=7) underwent modified GF placement in the IVC. Cavograms were obtained every 3 months and pulmonary angiography at 12 months. Histopathologic and scanning electron microscopy (SEM) analyses were performed on the IVC explanted at 12 months. RESULTS: Cavograms showed that all IVC were patent at the end of the study. Filter tilting occurred in 2/7 animals and extrusion of struts was not observed. Macroscopic examination at explantation showed minimal venous wall thickening. Microscopic examination showed minimal IVC fibrosis and intimal hyperplasia. SEM showed endothelium on the IVC surface at the filter implantation site and a presumed endothelial layer covering partially or totally the struts. The interface filter-IVC was covered by deposits of leucocytes and platelets. No signs of pulmonary embolism were found in all pulmonary angiograms of both groups. CONCLUSION: The modified filter presented good biocompatibility, stability and absence of thrombogenicity at 12 months. It presented low tendency to tilting and extrusion of struts. The long-term histopathologic alterations in vena caval wall were minimal and the appearance of the studied filters in the IVC was similar to stents placed in the arterial system.

Value of ultrasonographic contrast in duplex scanning of leg arteries. Comparison with conventional duplex scanning and arteriography.

AIM: Duplex scanning has been used in the evaluation of the aorta and proximal arteries of the lower extremities, but has limitations in evaluating the arteries of the leg. The utilization of ultrasonographic contrast (USC) may be helpful in improving the quality of the image in these arteries. The objective of the present study was to verify whether the USC increases the diagnostic accuracy of patency of the leg arteries and if it diminishes the time needed to perform duplex scanning. METHODS: Twenty patients with critical ischemia (20 lower extremities) were examined by standard duplex scanning, duplex scanning with contrast and digital subtraction arteriography (DSA). The 3 arteries of the leg were divided into 3 segments, for a total of 9 segments per limb. Each segment was evaluated for patency in order to compare the 3 diagnostic methods. Comparison was made between standard duplex scanning and duplex scanning with contrast in terms of quality of the color-coded Doppler signal and of the spectral curve, and also of the time to perform the exams. RESULTS: Duplex scanning with contrast was similar to arteriography in relation to patency diagnosis (p>0.3) and even superior in some of the segments. Standard duplex scanning was inferior to arteriography and to duplex scanning with contrast (p<0.001). There were improvements of 70% in intensity of the color-coded Doppler signal and 76% in the spectral curve after the utilization of contrast. The time necessary to perform the examinations was 23.7 minutes for standard duplex scanning and 16.9 minutes for duplex scanning with contrast (p<0.001). CONCLUSIONS: The use of ultrasonographic contrast increased the accuracy of the diagnosis of patency of leg arteries and diminished the time necessary for the execution of duplex scanning.

[Biomarkers of effects and susceptibility for risk assessment]. / Biomarcatori di effetto e di suscettibilità per la valutazione del rischio.

The ambient air of urban centres is polluted with potentially toxic chemicals mostly arising from the combustion or fuels used for transport, heating and industrial activities. Alongside the risk to the general public, atmospheric pollution could be considered an occupational health hazard to professional groups, such us traffic police or professional drivers working in urban areas. Molecular epidemiology can facilitate health risk assessment by investigating the relationship between exposure to environmental pollutants and quantification of biomarkers that lie on the pathway of carcinogenesis upstream of clinical disease. In particularly, biomarkers of early effects and susceptibility are playing an increase role in the investigation of the impact of air pollution on human carcinogenesis.

Healing process in anastomosis of homologous venous grafts preserved in glutaraldehyde implanted aorta of rabbits.

AIM: Autologous vein (AV) is sometimes not suitable or present for a vascular restoration. Homologous vein preserved in glutaraldehyde may be an alternative to AV, but little is yet known about this graft and its healing process after implantation in arteries. The purpose of this study was to compare the initial healing process of glutaraldehyde-tanned homologous venous grafts (group 1) with fresh autologous venous grafts (group 2), at 4 or 15 days. METHODS: Forty Norfolk rabbits were allocated in 2 groups of 20 animals each. The grafts was interposed in the infrarenal aorta of the rabbit. Anastomotic tensile strength (TS), hydroxyproline (HP) determination, and histology (HA) were performed. RESULTS: TS increased in both groups, from the 4th to 15th day, (p<0.01) in both proximal (G1: from 364.5+/-98.3 g to 491.8+/-107.3 g; G2: from 366.26+/-85.15 g to 518.46+/-82.79 g) and distal anastomosis (G1: from 363.53+/-96.26 g to 507.32+/-91.01 g; G2: from 352.30+/-102.41 g to 528.67+/-48.58 g), with no difference between the groups. HP did not change (p>0.10) in this same period and was similar in both groups, in the proximal (G1: from 677.99+/-153.98 microg/100 mg to 914.92+/-459.83 microg/100 mg; G2: from 668.65+/-170.28 microg/100 mg to 669.46+/-319.80 ug/100 mg) as well as in the distal anastomosis (G1: from 740.07+/-213.53 microg/100 mg to 923.52+/-270.57 microg/100 mg; G2: from 737.66+/-266.76 microg/100 mg to 707.68+/-171.25 microg/100 mg). Initial inflammatory and reparative features of the anastomosis were similar in both groups. CONCLUSION: We can conclude that the healing process of the glutaraldehyde-tanned homologous vein graft was similar to that of the fresh autologous venous graft.

Antithrombotic effect of Lonomia obliqua caterpillar bristle extract on experimental venous thrombosis.

The venom of Lonomia obliqua caterpillar may induce a hemorrhagic syndrome in humans, and blood incoagulability by afibrinogenemia when intravenously injected in laboratory animals. The possible antithrombotic and thrombolytic activities of L. obliqua caterpillar bristle extract (LOCBE) were evaluated in this study. The minimal intravenous dose of the extract necessary to induce afibrinogenemia and anticoagulation was 3.0 and 10.0 microg protein/kg body weight for rabbits and rats, respectively. In rabbits, this dose induced total blood incoagulability for at least 10 h and did not reduce the weight of preformed venous thrombi, in contrast to streptokinase (30,000 IU/kg). In rats, pretreatment with 5.0 and 10.0 microg/kg LOCBE prevented the formation of thrombi induced by venous stasis or by injury to the venous endothelium. The dose of 5.0 microg/kg LOCBE did not modify blood coagulation assay parameters but increased bleeding time and decreased plasma factor XIII concentration. When the extract was administered to rats at the dose of 10.0 microg/kg, the blood was totally incoagulable for 6 h. These data show that LOCBE was effective in preventing experimental venous thrombosis in rats, justifying further studies using purified fractions of the extract to clarify the mechanisms of this effect.

Antithrombotic effect of Lonomia obliqua caterpillar bristle extract on experimental venous thrombosis

The venom of Lonomia obliqua caterpillar may induce a hemorrhagic syndrome in humans, and blood incoagulability by afibrinogenemia when intravenously injected in laboratory animals. The possible antithrombotic and thrombolytic activities of L. obliqua caterpillar bristle extract (LOCBE) were evaluated in this study. The minimal intravenous dose of the extract necessary to induce afibrinogenemia and anticoagulation was 3.0 and 10.0 æg protein/kg body weight for rabbits and rats, respectively. In rabbits, this dose induced total blood incoagulability for at least 10 h and did not reduce the weight of preformed venous thrombi, in contrast to streptokinase (30,000 IU/kg). In rats, pretreatment with 5.0 and 10.0 æg/kg LOCBE prevented the formation of thrombi induced by venous stasis or by injury to the venous endothelium. The dose of 5.0 æg/kg LOCBE did not modify blood coagulation assay parameters but increased bleeding time and decreased plasma factor XIII concentration. When the extract was administered to rats at the dose of 10.0 æg/kg, the blood was totally incoagulable for 6 h. These data show that LOCBE was effective in preventing experimental venous thrombosis in rats, justifying further studies using purified fractions of the extract to clarify the mechanisms of this effect

Mutagenic and clastogenic activity of gastric juice in human gastric diseases.

To investigate whether subjects with low-acid states are exposed to increased genetic risk with respect to controls, we evaluated mutagenicity and presence of clastogenic factors (CF) in the gastric juice of chronic atrophic gastritis and omeprazole-treated patients. Mutagenic gastric juice was found in 8/15 (53%) chronic atrophic gastritis patients, 8/11 (73%) omeprazole-treated patients, and 2/13 (15%) healthy control subjects. The mean mutagenicity ratio of omeprazole-treated patients (1.52+/-0.48/0.1 ml gastric juice) was significantly higher than those of either controls (1.07+/-0.15; P<0.01) or chronic atrophic gastritis patients (1.16+/-0.21; P<0.05). Only chronic atrophic gastritis patients showed an increased clastogenic index with respect to healthy controls (2.67+/-2.13 versus 0.38+/-0.51; P<0.001). These findings expand our knowledge of gastric disease risk factors, and indicate that there may well be a risk of mucosal DNA damage arising from the presence of mutagenic and CF in the gastric juice.

Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis.

BACKGROUND AND OBJECTIVES: Thrombin activatable fibrinolysis inhibitor (TAFI) plays an important role in hemostasis, functioning as a potent fibrinolysis inhibitor. TAFI gene variations may contribute to plasma TAFI levels and thrombotic risk. DESIGN AND METHODS: We sequenced a 2083-bp region of the 5'-regulatory region of the TAFI gene in 127 healthy subjects searching for variations, and correlated identified polymorphisms with plasma TAFI levels. TAFI polymorphisms were examined as risk factors for venous thrombosis by determining their prevalence in 388 patients with deep venous thrombosis (DVT) and in 388 controls. RESULTS: Seven novel polymorphisms were identified: -152 A/G, -438 A/G, -530 C/T, -1053 T/C, -1102 T/G, -1690 G/A, and -1925 T/C. -152 A/G, -530 C/T and -1925 T/C were found to be in strong linkage disequilibrium, as were the -438 A/G, -1053 T/C, -1102 T/G and -1690 G/A. Plasma TAFI levels were higher in -438GG/-1053CC/-1102GG/-1690AA homozygotes than in -438AG/-1053TC/-1102TG/-1690GA heterozygotes, and -438AA/-1053TT/-1102TT/-1690GG homozygotes had the lowest TAFI levels (p=0.0003). TAFI concentrations in -152AA/-530CC/-1925TT homozygotes were somewhat higher but not significantly different from levels observed for -152AG/-530CT/-1925TC heterozygotes. Taken in combination, -438AG/-1053TC/-1102TG/-1690GA and -438AA/-1053TT/-1102TT/-1690GG yielded an OR for DVT of 0.8 (95%CI: 0.6-1). In subjects aged <35 years the OR was 0.7 (95%CI: 0.5-1.1). The OR for -152AG/-530CT/-1925TC was 1 (95%CI: 0.5-2.2) in the whole group of patients and controls, whereas in subjects aged <35 years the OR was 0.1 (95%CI: 0.02-0.9). INTERPRETATION AND CONCLUSIONS: Polymorphisms in the TAFI promoter determine plasma antigen levels and may influence the risk of venous thrombophilia.

Increased cytogenetic damage detected by FISH analysis on micronuclei in peripheral lymphocytes from alcoholics.

Alcohol abuse greatly increases the risk of various malignancies, including cancer of the liver and digestive tract. Although it is thought that this may be due, at least partially, to the mutagenic properties of ethanol, little is known about the genotoxic effects of ethanol in humans. We investigated the chromosomal damage in lymphocytes from 20 alcoholics and 20 controls using the micronucleus (MN) assay combined with fluorescence in situ hybridization (FISH) with a pancentromeric DNA probe capable of differentiating centromere positive (C+) from centromere negative (C-) MN. The frequency of MN in binucleate lymphocytes was significantly higher in alcoholics than in controls (12.0 +/- 5.4 and 7.6 +/- 1.6, respectively; P: < 0.05). FISH revealed significantly higher frequencies of C+ MN in alcoholics than in controls (8.2 +/- 4.8 and 3.4 +/- 1.4, respectively; P: < 0.05). In the alcoholics, no association was found between years of alcohol abuse and frequency of MN or C+ MN. However, age influenced MN and C+ MN frequency both in alcoholics and controls. These results indicate that alcohol abuse may well induce chromosome loss in humans, suggesting a possible aneugenic mechanism of alcohol. This effect could contribute to the health hazards related to alcoholism such as cancer risk.

Treatment of shigellosis with cefixime: two days vs. five days.

BACKGROUND: Although the recommended standard course of therapy for shigellosis is 5 days of oral ampicillin or trimethoprim-sulfamethoxazole therapy, successful outcome has been reported in adults treated with abbreviated courses of antibiotics. The purpose of this study was to compare short course (2-day) vs. 5-day therapy with cefixime for treatment of diarrheal disease caused by Shigella sonnei in children. METHODS: This was a prospective, randomized, double blind, placebo-controlled study. Patients were eligible if they were at least 6 months of age and presented to the Children's Hospital of Pittsburgh during an outbreak of diarrhea caused by S. sonnei, with (1) a history of fever and diarrhea (at least three loose or watery stools per day), (2) bloody diarrhea or (3) diarrhea and known exposure to an individual with documented shigellosis. Patients were randomized to receive either 2 days of cefixime (8 mg/kg(day) given once daily followed by 3 days of placebo or 5 days of cefixime. Telephone follow-up was performed on Days 3, 7 and 14 after enrollment. Follow-up stool cultures were obtained on Day 7 to assess bacteriologic cure. There were standardized definitions for cure, improvement, failure and relapse. RESULTS: Forty-seven patients were enrolled. Eleven were eliminated from analysis because their stool cultures were not positive for S. sonnei. There were 36 evaluable patients, 21 in the 2-day group and 15 in the 5-day group. Patients ranged in age from 6 months to 17 years. Forty-four percent of the subjects were male. Symptoms were improved or had resolved by Day 3 of therapy in all patients. There were 8 patients who experienced a clinical relapse: 5 of 21 (24%) patients in the 2-day treatment group and 3 of 15 (20%) in the 5-day group. There were 13 patients who experienced a bacteriologic failure (defined as the occurrence of a positive culture at the Day 7 follow-up visit), 11 of 20 (55%) in the 2-day group and 2 of 14 (14%) in the 5-day group (P < 0.02). CONCLUSION: Two- and 5-day treatment courses with cefixime for treatment of diarrheal disease caused by S. sonnei result in similar rates of clinical cure and clinical relapses; however, there was a higher rate of bacteriologic failure with shorter course therapy.

Indicators of genetic damage in alcoholics: reversibility after alcohol abstinence.

BACKGROUND/AIMS: Although a primary carcinogenic role of alcohol is not proven, alcohol abuse is associated with an increased risk of cancer of the upper airways, esophagus and liver. METHODOLOGY: Chromosome aberrations and the presence of micronuclei that reflect two types of genetic damage were analyzed in peripheral blood lymphocytes from 11 alcoholic patients who were heavy smokers and in a fair state of general nutrition and 9 subjects who had abstained from alcohol for at least a year. Ten heavy smokers were studied as healthy controls. RESULTS: Chromosome aberrations and micronuclei in alcoholics showed significantly elevated frequencies compared to the control groups, while in alcohol abstainers the values of all two parameters were similar to the values of the control subjects. CONCLUSIONS: These results show that long-term alcohol intake could induce genetic alterations in synergy with tobacco smoke. Interestingly, this damaging action is reversed by abstinence. Our results call for a further effort to find an eventual diagnostic role for these early genetic damage markers.