FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

Color flow Doppler characterization of focal hepatic lesions.

OBJECTIVE. The purpose of this study was to determine the sensitivity and specificity of color flow Doppler sonography for the specific diagnosis of focal hepatic lesions. SUBJECTS AND METHODS. Color flow Doppler images of 118 focal hepatic lesions in 108 patients were analyzed prospectively. In most patients, liver disease was suspected or known to be present before the Doppler images were obtained. Experienced sonologists obtained and interpreted all sonograms. The lesions were classified, according to their color flow pattern, into two main categories: lesions with internal vascularity and lesions with no internal vascularity. The color flow Doppler pattern of each lesion was correlated with the diagnosis of the lesion on a lesion-by-lesion basis. One hundred two lesions were proved by biopsy and 16 lesions were confirmed by evaluation with other imaging techniques. Lesions included 29 hepatocellular carcinomas, 64 metastases, one cholangiocarcinoma, and 24 benign lesions. The sensitivity and specificity of vascularity as shown by color Doppler imaging in the diagnosis of hepatocellular carcinoma were determined. RESULTS. The majority of hepatocellular carcinoma lesions (76%) had internal vascularity. Most of the metastases (67%) and benign lesions (75%) had no internal vascularity. When the presence of internal vascularity was used as the discriminating criterion, the sensitivity of color flow Doppler findings for the diagnosis of hepatocellular carcinoma was 0.76. The specificity of internal vascularity for the diagnosis of hepatocellular carcinoma vs other focal lesions was 0.69; for hepatocellular carcinoma vs metastases it was 0.67. CONCLUSION. Although most hepatocellular carcinomas have internal vascularity on color flow Doppler images, a significant number of metastases also have internal vascularity. This overlap limits the usefulness of color flow Doppler imaging for distinguishing hepatocellular carcinoma from metastatic tumors.     

用于筛选天然产物中脲酶抑制剂的脲酶活性测试方法的建立

抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Ｂｅｒｔｈｅｌｏｔ试剂在９６孔培养板上检测重组脲酶活性，其灵敏度指标酚红法每ｍｇ酶蛋白引起的每分钟吸光度变化。△Ａ为６．９，而Ｂｅｒｔｈｅｌｏｔ法每ｍｇ酶蛋白引起的每分钟吸光度比值变化△Ａ为３１３。结果表明用Ｂｅｒｔｈｅｌｏｔ试剂检测重组脲酶活性适宜在９６孔培养板上大规模筛选天然产物中的脲酶抑制剂。     

Uncomplicated amebic liver abscess: prospective evaluation of percutaneous therapeutic aspiration.

The performance of therapeutic aspiration in the treatment of amebic liver abscess, advocated and practiced in many centers, is controversial. Previously, this practice has been evaluated in retrospective analyses. To test the potential benefit of therapeutic aspiration, the authors undertook a prospective randomized trial in 57 patients admitted for suspected amebic liver abscess during a 15-month period. Sixteen patients were excluded from the trial. The remaining 41 patients were randomly included in one of two study groups to receive amebicidal therapy alone or amebicidal therapy coupled with image-guided percutaneous therapeutic aspiration. All patients in the trial recovered. No statistically significant benefit was demonstrated in the aspiration group for the two objective parameters evaluated: length of hospitalization and duration of time to becoming afebrile. Subjective improvement in symptoms after aspiration was greater in the aspiration group at a marginally statistically significant level. These data do not support the adjunctive performance of percutaneous therapeutic aspiration in the treatment of uncomplicated amebic liver abscess. Amebicidals alone were equally efficacious in treating the group studied.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Hepatic abscess

Hepatic abscess—amebic or pyogenic—can be diagnosed with great accuracy by either ultrasonography or computed tomographic (CT) scanning. Ultrasound is the modality of choice and will detect almost 100% of abscesses. Confirmation of a diagnosis of amebic liver abscess is made by the indirect hemagglutination test that should be positive in almost 100% of cases. Cultures of pus from the abscess and from the blood must be obtained in cases of pyogenic liver abscess. A positive culture of pus from the abscess has been achieved in 90% of cases. Ultrasound or CT guidance is utilized in aspiration of a hepatic abscess. In the treatment of an amebic liver abscess, metronidazole is the amebicide of choice. Open drainage is contraindicated. For cases that fail to respond to therapy with amebicides, closed drainage guided by CT or ultrasound is performed. Secondary bacterial infection of an amebic liver abscess is an extremely rare event. The identification and determination of the antibiotic sensitivity of organisms responsible for pyogenic liver abscess is a crucially important step. Unless a celiotomy is necessary to correct an intraabdominal process or the abscess is extremely large, the initial treatment of pyogenic liver abscess is a 2 week course of appropriate antibiotics followed by a 1 month course of oral antibiotics. The majority of pyogenic liver abscesses will respond to such treatment. If drainage of a pyogenic abscess is required, the preferable technique is with a percutaneous CT- or ultrasound-directed catheter. Open surgical drainage should be reserved for those cases in which a celiotomy is required for other purposes or for the patient who has failed a course of appropriate antibiotic therapy and closed percutaneous drainage is not feasible. The mortality for treatment of amebic liver abscess should be approximately zero and for pyogenic liver abscess should be less than 10%.

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Resumen El absceso hepático—amibiano o piogénico—puede ser diagnositicado con gran precisión mediante la ultrasonografía (US) o la tomografía computadorizada (TC). La ultrasonografía es la modalidad de escogencia; détecta casí el 100% de los abscesos. La confirmación del diagnóstico de absceso amibiano del hígado se hace por la prueba de hemaglutinación indirecta, la cual debe resultar positiva en prácticamente el 100% de los casos. Cultivos del pus y de la sangre deben ser realizados en los pacientes con abscesos piógenos. Se logran cultivos positivos del pus del absceso en 90% de los casos. Se utiliza la guía ultrasonográfica o de tomografía computadorizada para la aspiración del absceso.El metronidazol es el agente amebicida de preferencia en el tratamiento del absceso amibiano del hígado. El drenaje abierto está contraindicado. En los casos en que falla la terapia con amibicidos, se realiza el drenaje cerrado guiado por US o por TC. La infección secundaria de un absceso amibiano del hígado es un fenómeno extraordinariamente raro.La identificatión y determinatión de la sensibilidad antibiótica de los microorganismos responsables del absceso piógeno representa un paso crucial en su manejo. A menos que se haga necesario realizar una laparotomía para la correción del algún proceso intraabdominal o porque el absceso es excesivamente grande, el tratamiento inicial del absceso piógeno es un ciclo de antibióticos propiados de 2 semanas, seguidos de tratamiento con antibióticos orales por un mes. La mayoría de los abscesos piógenos del hígado responde a este tipo de tratamiento. Si se requiere drenaje de un absceso piógeno, la técnica de preferencia es la punción percutánea por medio de un catéter guiado por US o TC. El drenaje quirúrgico abierto debe reservarse para aquellos casos en que la laparatomía es necesaria por razones diferentes o en que hay falla en la respuesta a un ciclo de terapia antibiótica adecuada y el drenaje percutáneo no es factible.La mortalidad en el manejo del absceso amibiano del hígado debe ser nula, y para el absceso piógeno de menos de 10%.

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Résumé L'abcès hépatique amibien ou à pyogènes peut être diagnostiqué avec une grande précision soit par l'échographie, soit par la tomodensitométrie. L'échographie est la méthode de choix et détecte presque 100% des abcès. On obtient la confirmation du diagnostic d'abcès amibien par le test d'hémagglutination indirecte qui est positive dans presque 100% des cas. On doit faire des cultures de pus provenan de l'abcès et des hémocultures en cas d'abcès à pyogènes du foie. Ces cultures ont été positives dans 90% des cas. L'échographie et la tomodensitométrie aident à guider le drainage de abcès.Dans le traitement de l'abcès amibien du foie, le métronidazole est l'amibicide de choix. Le drainage à ciel ouvert est contreindiqué. Pour les cas qui ne répondent pas aux amibicides, un drainage percutané guidé par la tomodensitométrie ou l'échographie est indiqué. La surinfection d'un abcès amibien du foie est extrêmement rare.L'identification et la détermination de la sensibilité aux antibiotiques des organismes responsables de l'abcès à pyogènes est une étape extrêmement importante. A moins qu'une laparotomie soit nécessaire pour traiter une infection intraabdominale associée ou que le volume de l'abcès soit extrêmement important, le traitement initial d'un abcès à pyogènes comprend 2 semaines d'antibiotiques adaptés par voie générale suivies d'un mois d'antibiotiques par voie orale. La plupart des abcès à pyogènes répondront bien à ce traitement. Si le drainage d'un abcès à pyogènes s'avère nécessaire, la meilleure technique est percutanée avec un cathéter inséré sous contrôle tomodensitométrique ou échographique. On réservera le drainage chirurgical à ciel ouvert aux cas où une laparotomie est nécessaire pour d'autres raisons et où le malade n'a pas répondu à l'antibiothérapie adaptée et chez qui le drainage percutané est impossible à faire.La mortalité de l'abcès amibien traité devrait approcher 0% et atteindre pour l'abcès à pyogènes moins de 10%.

     

Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.