Pharmacological Characterization and Raman Spectroscopy Evaluation of Oral and Maxillofacial Surgery-Related Carnoy´S Solution Modified by Different Viscosity Agents.

BACKGROUND: There are several lesions of odontogenic and non-odontogenic origin in the oral cavity, such as odontogenic keratocyst, as well as many treatment options for such lesions. In order to reduce recurrence due to conservative treatments and less aesthetic and functional impairment of the patient (radical therapies), Carnoy's solution has been used as an adjuvant to surgery, showing satisfactory results. Its application is not standardized, presenting risks to adjacent tissues. Thus, we characterized the Carnoy's solution with different viscosity agents to enhance its applicability. MATERIAL AND METHODS: All solutions prepared (Carnoy with and without chloroform) were added with viscosity agent: ethyl cellulose, propylene glycol, and glycerol totaling eight solutions. The pharmacological characterization of the solutions was performed by determining the mass density and relative density (using a clean and dry pycnometer), pH (using pH meter), and concentration of Fe3+ (using ultraviolet/visible spectroscopy). The analyses of the inorganic components were determined by Raman micro spectrometry. Data were analyzed with statistical program BIOESTAT 5.3. RESULTS: Solutions with ethyl cellulose were discarded due to precipitate formation and suspension of the viscosity agent. In the other solutions, viscosity increase (propylene glycol solutions) and acidic pH were observed mainly in the glycerol group. The ferric chloride characterized as a hemostatic agent had its concentration increased with the use of thickening agents, theoretically favoring its action. CONCLUSION: The similarity of the propylene glycol and glycerol molecules justifies the Raman spectra of these substances to be similar and the difficulty in obtaining a "fingerprint".
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Assessment of indirect inhalation exposure to formaldehyde evaporated from water.

Volatilization volumes and health risks associated with indirect inhalation exposure to formaldehyde evaporated from water have not been investigated quantitatively. We experimentally investigated formaldehyde volatility, compared with chloroform volatility, predicted formaldehyde inhalation exposure concentrations in Japanese bathrooms, and then re-evaluated drinking water quality standards. Although the Henry's law constant of formaldehyde is 1/104 that of chloroform, with a 30-min exposure period, the formaldehyde non-equilibrium partition coefficient (K'd) was 1/500th the chloroform value because of formaldehyde's faster volatilization rate. We used this ratio to estimate the cumulative probability distribution of formaldehyde concentrations in bathroom air. For a formaldehyde concentration in water of ≤2.6 mg/L-water (WHO tolerable concentration), the probability that the incremental formaldehyde concentration due to volatilization would exceed 100 µg/m3-air (WHO indoor air quality guideline) was low. However, major sources of formaldehyde in indoor air are building materials and furniture. We therefore calculated the allowable concentration in water by allocating a small percentage of the indoor air guideline value to indirect inhalation exposure via volatilization from tap water. With an allocation factor of 20% (10%), the allowable concentration was 0.52 (0.26) mg/L-water. These concentrations are similar to the Health Canada guideline concentration but they are 3-6 times the Japanese water quality standard.

Evaluation of antitumour activity of Calotropis gigantea L. root bark against Ehrlich ascites carcinoma in Swiss albino mice.

OBJECTIVE: To investigate experimentally the possible antitumor effect of methanol extract (ME) of Calotropis gigantea L. (C. gigantean) root bark and its petroleum ether (PEF) and chloroform (CF) soluble fractions against Ehrlich ascites carcinoma (EAC) in Swiss albino mice. METHODS: The effects of ME (10 and 20 mg/kg), PEF (40 and 80 mg/kg) and CF (20 and 40 mg/kg) on the growth of EAC and life span of EAC bearing mice were studied. Hematological profile and biochemical parameters (SALP, SGPT and SGOT) were also estimated. RESULTS: Results of in vivo study showed a significant decrease in viable tumor cell count and a significant increase of life span in the ME and CF treated group compared to untreated one. The life span of ME and CF treated animals was significantly (P<0.05) increased by 43.90% (20 mg ME/kg) and 57.07% (40 mg CF/kg). ME and CF brought back the hematological parameter more or less normal level. ME and CF also restored the altered levels of serum alkaline phosphatase (SALP) and serum glutamate oxaloacetate transaminase (SGOT). CONCLUSIONS: Methanol extract (ME) of C. gigantea root bark and its chloroform soluble fraction (CF) possesses significant antitumor activity.

La primera anestesia filmada en el mundo se hizo en Buenos Aires / The first filmed anesthesia in the world took place in Buenos Aires

En el año 1899, en el viejo Hospital de Clínicas de Buenos Aires Eugenio Py filmó una intervención quirúrgica que practicó el Dr. Alejandro Posadas para resecar un quiste hidatídico de pulmón. En la película se ve a Posadas operando, y administrando la anestesia al Practicante Rodolfo S. Roccatagliata que tiene en su mano derecha un frasco, del cual deja caer esporádicamente un fármaco sobre una máscara anestésica. Es probable que la anestesia se realizó con el cloroformo y la máscara de Schimmelbusch. En las conclusiones, se considera que esta película testimonia que la primera filmación de una anestesia general en el mundo se hizo en Buenos Aires.

In 1899 at the old Hospital de Clínicas in Buenos Aires, Eugenio Py filmed a surgical procedure performed by Dr. Alejandro Posadas to extirpate a lung hydatid cyst. The film shows Posadas operating and Rodolfo S. Roccatagliata administering anesthesia, holding in his right hand a bottle from which he sporadically drops a drug to an anesthetic mask. It is probable that the anesthetic was chloroform, and the mask that of Schimmelbusch. The conclusion is that that this film is proof of being the first one of general anesthesia in the world, taken in Buenos Aires.

Em 1899, no velho Hospital de Clínicas de Buenos Aires, Eugenio Py filmou uma intervenção cirúrgica realizada pelo Dr. Alejandro Posadas para resseção de um cisto hidático de pulmão. No filme se vê ao Dr. Posadas operando e ao praticante Rodolfo S. Roccatagliata administrando a anestesia, quem tem um frasco na mão direita do qual cai, esporadicamente, um fármaco a uma máscara anestésica. É provável que o anestésico fosse o clorofórmio e a máscara, a de Schimmelbusch. Nas conclusões se considera que este filme é um testemunho de que a primeira filmagem de uma anestesia geral no mundo foi feita em Buenos Aires.

Evaluation of the impact of the exposure route on the human kinetic adjustment factor.

The objective of this study was to assess the impact of the exposure route on the human kinetic adjustment factor (HKAF), for which a default value of 3.16 is used in non-cancer risk assessment. A multi-route PBPK model was modified from the literature and used for computing the internal dose metrics in adults, neonates, children, elderly and pregnant women following three route-specific scenarios to chloroform, bromoform, tri- or per-chloroethylene (TCE or PERC). These include 24-h inhalation exposure, body-weight adjusted oral exposure and 30 min dermal exposure to contaminated drinking water. Distributions for body weight (BW), height (BH) and hepatic cytochrome P450 2E1 (CYP2E1) content were obtained from the literature, whereas model parameters (flows, volumes) were calculated from BW and BH. Monte Carlo simulations were performed and the HKAF was calculated as the ratio of the 95th percentile value of internal dose metrics in subpopulation to the 50th percentile value in adults. On the basis of the area under the parent compound's arterial blood concentration vs time curve (AUC(pc)), highest HKAFs were obtained in neonates for every scenario considered, and were the highest for bromoform (range: 3.6-7.4). Exceedance of the default value based on AUC(PC) was also observed for an oral exposure to chloroform in neonates (4.9). In all other cases, HKAFs remained below the default value. Overall, this study has pointed out the dependency of the HKAF on the exposure route, dose metrics and subpopulation considered, as well as characteristics of the chemicals investigated.

Chloroform distribution and accumulation by combined inhalation plus oral exposure routes in rats.

The present investigation was undertaken to determine the distribution and accumulation of chloroform in the blood, liver, kidney and abdominal fat of rats after simultaneous exposure by two routes, inhalation and oral. To distinguish the contribution of each route, unmodified chloroform (CHCl3) was administered by inhalation and deuterated chloroform (CDCl3) was administered orally. Exposure by inhalation and oral administration resulted in CHCl3 and CDCl3 concentrations in the tissues which were significantly higher than when exposure was by either inhalation or oral administration alone. This is the first study to follow the contribution of each of two routes of chloroform exposure on chloroform distribution and accumulation in target tissues. Our results indicate that when assessing the toxicity and carcinogenicity of chloroform, exposure routes, especially the effects of exposure by multiple routes, must be taken into consideration.

[Marsupialization and enucleation of keratocystic odontogenic tumor with the use of Carnoy's solution].

INTRODUCTION: Keratocystic odontogenic tumors (KCOT) or odontogenic keratocysts are aggressive and expansive odontogenic neoplasms with high recurrence rate (25%-60%). There are a small number of publications about the combination of marsupialization and enucleation with the use of Carnoy's solution for the treatment of KCOT. CASE REPORT: In a female patient, aged 24, marsupialization KCOT was done in the first stage, and enucleation with the use of Carnoy's solution in the second stage, six months later. Lost sensibility of the lower lip was reestablished after three months. A postoperation defect was completely filled in seven months. One year later orthopantomographic x-ray showed the presence of a newly formed bone tissue, whereas in 7 years a completely preserved new mandibular bone and recanalisation of mandibular canal were observed. CONCLUSION: We consider that our method was successful in the treatment of KCOT, with no occurrence of recidives seven years later. However, it is necessary to follow the patient periodically because of a possible late recidive.

Histerocele total complicado con miasis a propósito de un caso / Histerocele myiasis complicated by a total of one case

Miasis es la infestación de órganos o tejidos por larvas de moscas. La infestación con larvas de mosca produce diversas manifestaciones según el sitio afectado y puede incluso, causar la muerte. No es una enfermedad común en humanos pero se observa con alguna regularidad en países neotropicales. Afecta con mayor frecuencia las áreas expuestas de la piel y se presenta raramente en ojos, nariz, senos paranasales, tracto urogenital o recto; en estos casos la infestación se asocia con traumas previos o secresiones purulentas que atraen a las moscas adultas. Se presenta el caso de una paciente femenina de 65 años de edad, con prolapso total del útero (histerocele grado IV) complicado con miasis específica por Cochliomya hominivorax.

Further studies on the hepatoprotective effects of Anoectochilus formosanus.

The purpose of this study was to investigate the hepatoprotective effects of Anoectochilus formosanus effective fraction (AFEF) on chronic liver damage induced by carbon tetrachloride (CCl4) in mice. CCl4 (5%; 0.1 mL/10 g body weight) was given twice a week for 9 weeks, and mice received AFEF throughout the whole experimental period. Plasma GPT, hepatic levels of hydroxyproline and malondialdehyde were significantly lower in mice treated with AFEF compared with those treated with CCl4 only. Liver pathology in the AFEF-treated mice was also improved. RT-PCR analysis showed that AFEF treatment increased the expression of methionine adenosyltransferase 1A and decreased the expression of collagen(alpha1)(I) and transforming growth factor-beta1. These results clearly demonstrated that AFEF reduced the hepatic damage induced by CCl4 in mice.

Enhancement of renal carcinogenicity by combined inhalation and oral exposures to chloroform in male rats.

Chloroform, ubiquitously present in indoor and outdoor air, drinking water, and some foodstuffs, enters the human body by inhalation, oral and dermal routes of exposure. In order to provide bioassay data for risk assessment of humans exposed to chloroform by multiple routes, effects of combined inhalation and oral exposures to chloroform on carcinogenicity and chronic toxicity in male F344 rats were examined. A group of 50 male rats was exposed by inhalation to 0 (clean air), 25, 50, or 100 ppm (v/v) of chloroform vapor-containing air for 6 h/d and 5 d/wk during a 104 w period, and each inhalation group was given chloroform-formulated drinking water (1000 ppm w/w) or vehicle water for 104 wk, ad libitum. Renal-cell adenomas and carcinomas and atypical renal-tubule hyperplasias were increased in the combined inhalation and oral exposure groups, but not in the oral- or inhalation-alone groups. Incidences of cytoplasmic basophilia and dilated tubular lumens in the kidney, as well as incidence of positive urinary glucose, were markedly increased by the combined exposures, compared with those after single-route exposures. It was concluded that combined inhalation and oral exposures markedly enhanced carcinogenicity and chronic toxicity in the proximal tubule of male rat kidneys, suggesting that carcinogenic and toxic effects of the combined exposures on the kidneys were greater than the ones that would be expected under an assumption that the two effects of single route exposures through inhalation and drinking were additive.

Subchronic chloroform priming protects mice from a subsequently administered lethal dose of chloroform.

Protection offered by pre-exposure priming with a small dose of a toxicant against the toxic and lethal effects of a subsequently administered high dose of the same toxicant is autoprotection. Although autoprotection has been extensively studied with diverse toxicants in acute exposure regimen, not much is known about autoprotection after priming with repeated exposure. The objective of this study was to investigate this concept following repeated exposure to a common water contaminant, chloroform. Swiss Webster (SW) mice, exposed continuously to either vehicle (5% Emulphor, unprimed) or chloroform (150 mg/kg/day po, primed) for 30 days, were challenged with a normally lethal dose of chloroform (750 mg chloroform/kg po) 24 h after the last exposure. As expected, 90% of the unprimed mice died between 48 and 96 h after administration of the lethal dose in contrast to 100% survival of mice primed with chloroform. Time course studies indicated lower hepato- and nephrotoxicity in primed mice as compared to unprimed mice. Hepatic CYP2E1, glutathione levels (GSH), and covalent binding of (14)C-chloroform-derived radiolabel did not differ between livers of unprimed and primed mice after lethal dose exposure, indicating that protection in liver is neither due to decreased bioactivation nor increased detoxification. Kidney GSH and glutathione reductase activity were upregulated, with a concomitant reduction in oxidized glutathione in the primed mice following lethal dose challenge, leading to decreased renal covalent binding of (14)C-chloroform-derived radiolabel, in the absence of any change in CYP2E1 levels. Buthionine sulfoximine (BSO) intervention led to 70% mortality in primed mice challenged with lethal dose. These data suggest that higher detoxification may play a role in the lower initiation of kidney injury observed in primed mice. Exposure of primed mice to a lethal dose of chloroform led to 40% lower chloroform levels (AUC(15-360 min)) in the systemic circulation. Exhalation of (14)C-chloroform was unchanged in primed as compared to unprimed mice (AUC(1-6 h)). Urinary excretion of (14)C-chloroform was higher in primed mice after administration of the lethal dose. However, neither slightly higher urinary elimination nor unchanged expiration can account for the difference in systemic levels of chloroform. Liver and kidney regeneration was inhibited by the lethal dose in unprimed mice leading to progressive injury, organ failure, and 90% mortality. In contrast, sustained and highly stimulated compensatory hepato- and nephrogenic repair prevented the progression of injury resulting in 100% survival of primed mice challenged with the lethal dose. These findings affirm the critical role of tissue regeneration and favorable detoxification (only in kidney) of the lethal dose of chloroform in subchronic chloroform priming-induced autoprotection.

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay.

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 microL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

In vitro cytotoxic and non-genotoxic effects of gutta-percha solvents on mouse lymphoma cells by single cell gel (comet) assay

Chloroform and eucalyptol are widely used in clinical dentistry as gutta-percha solvents. However, these compounds may represent a hazard to human health, especially by causing injury to genetic apparatus and/or inducing cellular death. In this study, the genotoxic and cytotoxic potentials associated with exposure to chloroform and eucalyptol were assessed on mouse lymphoma cells in vitro by the single cell gel (comet) assay and trypan blue exclusion test, respectively. Both gutta-percha solvents proved to be cytotoxic at the same levels in concentrations of 2.5, 5 and 10 muL/mL (p<0.05). On the other hand, neither of the solvents induced DNA breakage. Taken together, these results suggest that although both tested compounds (chloroform and eucalyptol) are strong cytotoxicants, it seems that they are not likely to increase the level of DNA damage on mammalian cells.

Clorofórmio e eucaliptol são amplamente utilizados na clínica odontológica como solventes de guta-percha. Entretanto, estes compostos podem representar um perigo à saúde humana, especialmente por causar danos ao aparelho genético e/ou induzir morte celular. Neste estudo, o potencial genotóxico e citotóxico associado à exposição ao clorofórmio e eucaliptol foram avaliados em células de linfoma murino in vitro pelo teste de células individualizadas (teste do cometa) e pelo teste do azul de tripan, respectivamente. Ambos os solventes de guta-percha provaram ser citotóxicos nos mesmos níveis em concentrações de 2,5, 5 e 10 miL/mL (p<0.05). Por outro lado, nenhum dos dois solventes induziu danos ao DNA. Em conclusão, esses resultados sugerem que ambos os compostos testados (clorofórmio e eucaliptol) são potentes citotoxinas, mas não representam um fator que aumenta o nível de danos no DNA em células de mamíferos.

A retrospective review of treatment of the odontogenic keratocyst.

PURPOSE: The purpose of this study was to evaluate different surgical treatment methods for odontogenic keratocysts and the outcome of those treatments over a 25-year period. PATIENTS AND METHODS: A retrospective review was performed of 40 patient charts treated at the University of Iowa Hospitals and Clinics (Iowa City, IA) from 1977 to 2002 with the diagnosis of odontogenic keratocyst. Demographic data were collected along with lesion location, symptoms present at initial presentation, surgical treatment rendered, length of follow-up, and incidence of recurrence. RESULTS: Surgical treatments included enucleation, enucleation with Carnoy's solution, peripheral ostectomy, peripheral ostectomy with Carnoy's solution, and en bloc resection. Recurrence was found in 9 to 40 patients. Seven of 9 recurrences (78%) occurred in 5 years or less, with 2 (22%) occurring more than 5 years after initial treatment. Patients treated with enucleation had a recurrence rate of 54.5% (6 of 11 patients). One of 2 patients treated with enucleation and Carnoy's solution had a recurrence. Those treated with peripheral ostectomy had a recurrence rate of 18.2% (2 of 11). Peripheral ostectomy with Carnoy's solution had no recurrences (0/13). CONCLUSION: Treatment of an odontogenic keratocyst with peripheral ostectomy, with or without the use of Carnoy's solution, had a significantly lower rate of recurrence. Treatment with enucleation, with or without the use of Carnoy's solution was associated with a significantly higher recurrence rate.

Cytotoxicity evaluation of gutta-percha solvents: Chloroform and GP-Solvent (limonene).

OBJECTIVE: The purpose of this study was to compare the cytotoxicity of 2 gutta-percha solvents, chloroform and GP-Solvent, on cell line L929. STUDY DESIGN: 2 gutta-percha solvents were diluted into the concentrations of 1:100, 1:400, and 1:800. The experiment was done in a 96-well tissue-culture plate. Cell viability of L929 was determined after each gutta-percha solvent was left in contact with MTT solution for 3 hours. RESULTS: Both solvents proved toxic at the same levels of concentrations of 1:100 and 1:400 (P>.05). At the dilution of 1:800 the GP-Solvent seems to be more toxic than the chloroform (P < .05). CONCLUSIONS: Within the limitation of this experiment, GP-Solvent was not less cytotoxic than chloroform to the target cells. Because in clinical procedures we use a higher concentration of solvent to dissolve gutta-percha for retreatment than that used in this study, the overflowing of liquefied gutta-percha, or solvent out of apical foramen, should be a cause for concern.

Biologically motivated computational modeling of chloroform cytolethality and regenerative cellular proliferation.

Chloroform is a nongenotoxic-cytotoxic carcinogen in rodents. As such, events related to cytotoxicity are the driving force for cancer induction. In this paper we extended an existing physiologically based pharmacokinetic (PBPK) model for chloroform to describe a plausible mechanism linking the hepatic metabolism of chloroform to hepatocellular killing and regenerative proliferation. The key aspects of this mechanism are (1) the production of damage at a rate proportional to the rate of metabolism predicted by the PBPK model, (2) the saturable repair of the damage, (3) the stimulation of the cell death rate by damage, and (4) the stimulation of the cell division rate as a function of the difference between the control and exposed numbers of cells. This extension allows the simulation of the labeling index and comparison with labeling index data. Data from a previously published chloroform-inhalation study with female B6C3F1 mice that determined cytolethality and regenerative cellular proliferation following exposures of varying concentrations and exposure durations were used for model calibration. Both threshold and low-dose linear linkages between chloroform-induced damage and cell death rate provided visually good fits to the labeling index data after formal optimization of the adjustable parameters, and there was no statistical difference between the fits of the two models to the data. Biologically motivated computational modeling of chloroform-induced cytolethality and regenerative proliferation is a necessary step in the quantitative evaluation of the hypothesis that chloroform-stimulated cell proliferation predicts the rodent tumor response.

What to do at low doses: a bounding approach for economic analysis.

To quantify the health benefits of environmental policies, economists generally require estimates of the reduced probability of illness or death. For policies that reduce exposure to carcinogenic substances, these estimates traditionally have been obtained through the linear extrapolation of experimental dose-response data to low-exposure scenarios as described in the U.S. Environmental Protection Agency's Guidelines for Carcinogen Risk Assessment (1986). In response to evolving scientific knowledge, EPA proposed revisions to the guidelines in 1996. Under the proposed revisions, dose-response relationships would not be estimated for carcinogens thought to exhibit nonlinear modes of action. Such a change in cancer-risk assessment methods and outputs will likely have serious consequences for how benefit-cost analyses of policies aimed at reducing cancer risks are conducted. Any tendency for reduced quantification of effects in environmental risk assessments, such as those contemplated in the revisions to EPA's cancer-risk assessment guidelines, impedes the ability of economic analysts to respond to increasing calls for benefit-cost analysis. This article examines the implications for benefit-cost analysis of carcinogenic exposures of the proposed changes to the 1986 Guidelines and proposes an approach for bounding dose-response relationships when no biologically based models are available. In spite of the more limited quantitative information provided in a carcinogen risk assessment under the proposed revisions to the guidelines, we argue that reasonable bounds on dose-response relationships can be estimated for low-level exposures to nonlinear carcinogens. This approach yields estimates of reduced illness for use in a benefit-cost analysis while incorporating evidence of nonlinearities in the dose-response relationship. As an illustration, the bounding approach is applied to the case of chloroform exposure.

Chronic toxicity of chloroform to Japanese medaka fish.

Japanese medaka (Oryzias latipes) were continually exposed in a flow-through diluter system for 9 months to measured chloroform concentrations of 0.017, 0.151, or 1.463 mg/L. Parameters evaluated were hepatocarcinogenicity, hepatocellular proliferation, hematology, and intrahepatic chloroform concentration. Histopathology was evaluated at 6 and 9 months. Chloroform was not hepatocarcinogenic to the medaka at the concentrations tested. Chronic toxicity was evidenced at these time points by statistically significant ([alpha] = 0.05) levels of gallbladder lesions and bile duct abnormalities in medaka treated with 1.463 mg/L chloroform. We assessed hepatocellular proliferation by exposing test fish to 5-bromo-2'-deoxyuridine in the aquarium water for 72 hr after 4 and 20 days of chloroform exposure; we then quantified area-labeling indices of the livers using computer-assisted image analysis. We observed no treatment-related increases in cellular proliferation. We analyzed cells in circulating blood in medaka after 6 months of chloroform exposure. Hematocrit, leukocrit, cell viability, and cell counts of treated fish were not significantly different from those of control fish. Using gas chromatography (GC), we evaluated intrahepatic concentrations of chloroform in fish after 9 months of exposure. Livers from the 0.151 and 1.463 mg/L chloroform-treated fish had detectable amounts of chloroform, but these levels were always lower than the aquaria concentrations of chloroform. Thus, it appeared that chloroform did not bioaccumulate in the liver. Unidentified presumptive metabolite peaks were found in the GC tracings of these fish livers.

A history of the dissolution of retained choledocholithiasis.

BACKGROUND: Common duct calculi retained after gallbladder surgery continue to present a clinical challenge especially in the era of minimally invasive surgery. This review examines the strategy of dissolution therapy used throughout the history of biliary tract surgery and its use to the modern surgeon. DATA SOURCES: Original journal articles and reviews were identified using standard surgical textbooks and MEDLINE. Keywords for searching included choledocholithiasis, dissolution, mono-octanoin, common duct stones, MTBE, cholic acid, and gallstones. CONCLUSIONS: Dissolution therapy used initially as an alternative to open surgery is now used more effectively as an adjunct to laparoscopic or endoscopic biliary tract surgery. The current review demonstrates a majority of patients with retained choledocholithiasis respond to dissolution and can be safely managed without choledochotomy.

Metabolism of chloroform by cytochrome P450 2E1 is required for induction of toxicity in the liver, kidney, and nose of male mice.

Chloroform is a nongenotoxic-cytotoxic liver and kidney carcinogen and nasal toxicant in some strains and sexes of rodents. Substantial evidence indicates that tumor induction is secondary to events associated with cytolethality and regenerative cell proliferation. Therefore, pathways leading to toxicity, such as metabolic activation, become critical information in mechanism-based risk assessments. The purpose of this study was to determine the degree to which chloroform-induced cytotoxicity is dependent on the cytochromes P450 in general and P450 2E1 in particular. Male B6C3F(1), Sv/129 wild-type (Cyp2e1+/+), and Sv/129 CYP2E1 knockout (Cyp2e1-/- or Cyp2e1-null) mice were exposed 6 h/day for 4 consecutive days to 90 ppm chloroform by inhalation. Parallel control and treated groups, excluding Cyp2e1-null mice, also received an i.p. injection (150 mg/kg) of the irreversible cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) twice on the day before exposures began and 1 h before every exposure. Cells in S-phase were labeled by infusion of BrdU via an implanted osmotic pump for 3.5 days prior to necropsy, and the labeling index was quantified immunohistochemically. B6C3F(1) and Sv/129 wild-type mice exposed to chloroform alone had extensive hepatic and renal necrosis with significant regenerative cell proliferation. These animals had minimal toxicity in the nasal turbinates with focal periosteal cell proliferation. Administration of ABT completely protected against the hepatic, renal, and nasal toxic effects of chloroform. Induced pathological changes and regenerative cell proliferation were absent in these target sites in Cyp2e1-/- mice exposed to 90 ppm chloroform. These findings indicate that metabolism is obligatory for the development of chloroform-induced hepatic, renal, and nasal toxicity and that cytochrome P450 2E1 appears to be the only enzyme responsible for this cytotoxic-related metabolic conversion under these exposure conditions.