Surgical resection for non-Asian intrahepatic lithiasis: The Brazilian experience

BackgroundIntrahepatic lithiasis (IHL) is a rare disease in the western world. Complications associated with IHL include acute cholangitis, liver atrophy, secondary biliary cirrhosis, and risk for intrahepatic cholangiocarcinoma. Liver resection is considered the treatment of choice for IHL. The objective of this study was to analyze patients who underwent liver resection for non-Asian hepatolithiasis.Methods127 patients with symptomatic non-Asian hepatolithiasis underwent resection in six institutions. Demographic data, clinical presentation, diagnosis, classification according to stone location, presence of atrophy, bile duct stricture, biliary cirrhosis, incidence of cholangiocarcinoma, treatment and postoperative course were evaluated.Results52 patients (40.9%) were male and the mean age was 46.1 years. Sixty-six patients (51.9%) presented with history of cholangitis. Stones were located in the left lobe in 63 (49.6%), and right lobe in 28 patients (22.0%). Atrophy was observed in 31 patients (24.4%) and biliary stenosis in 18 patients (14.1%). The most common procedure performed was left lateral sectionectomy in 63 (49.6%) patients, followed by left hepatectomy in 36 (28.3%), right hepatectomy in 19 (15.0%), and associated hepaticojejunostomy in 28 (22.0%). Forty-two patients (33.0%) presented postoperative complications and the most common were biliary fistula (13.3%) and surgical site infection (7.0%). Postoperative mortality was 0.7%. Intrahepatic cholangiocarcinoma was observed in 2 patients (1.5%). Recurrence was identified in 10 patients (7.8%), mostly with bilateral stones and/or hepaticojejunostomy.ConclusionLiver resection is the standard treatment for symptomatic unilateral or complicated IHL with good operative results. Risk of cholangiocarcinoma was low in non-Asian patients.     

Iterative reconstruction algorithms

In this paper a survey of recent results on iterative reconstruction algorithms is given. These results, many of which have not yet appeared elsewhere, are applicable to a very general formulation of the reconstruction problem based on the series expansion approach. A set of optimization criteria and a number of iterative reconstruction algorithms are stated, together with theorems on the convergence of the algorithms to optimum images. The efficacy of the algorithms is compared to that of the convolution method. In particular, the falseness of the claim that ART and the backprojection method are the same is demonstrated.     

Factors Influencing the Growth in Knowledge of Trainees in General Practice

Objectives: The relation between the content of postgraduate training for general practice and the outcome in terms of the growth in knowledge of trainees was investigated. The training variables included were: (1) the number of patients seen per day, (2) the trainer, (3) the practice and (4) the theoretical curriculum.Methods: Subjects were 58 trainee-trainer pairs. Growth in knowledge was assessed by two written tests administered with eight months interval. Training variables were evaluated by means of questionnaires and logbook-registration. The correlation was explored between each of the training variables and the knowledge tests scores. To correct for interactional effects, a step-wise multiple regression analysis was performed with the second test as dependent variable and the first test as well as the training variables as independent variables.Results: Significant growth in knowledge was demonstrated. Non of all training variables investigated explained the variance in scores on the second test equally good or better than the scores on the entry test.Conclusions: The impact of the separate training-components on the growth in knowledge, remains unclear. We may speculate, that the sort of knowledge assessed with the written literature based true/false test is different from the sort of knowledge transferred during every day training: evidence based knowledge versus experience based knowledge. Equally valid is the conclusion that these findings fit into the theory that in adult learning the outcome is more learner than teacher dependent.This revised version was published online in September 2005 with corrections to the Cover Date.     

Modulation of [cis-diaminedichloroplatinum(ii) hyperthermia] therapy by inhibitors of arachidonic-Acid metabolism

Previous studies have shown that hyperthermia is an effective modulator of cis-diamminedichloroplatinum(II) (CDDP) cytotoxicity. We have examined the potential of inhibitors of the arachidonic acid metabolism to increase the antitumor activity of CDDP and hyperthermia. Sulindac and diflunisal are cyclooxygenase inhibiting non-steroidal anti-inflammatory drugs (NSAIDS) and phenidone is a lipoxygenase inhibitor. Using the FSaIIC in vivo-in vitro excision assay, neither five daily injections of sulindac nor diflunisal added to the killing of FSaIIC cells achieved by one injection of CDDP at normal temperature. When the i.p. injection of CDDP and the NSAIDS were followed immediately by hyperthermia treatment to the tumor bearing limb at 43-degrees-C for 30 min, the cell killing achieved was increased by 2-3-fold by diflunisal over the dose range of CDDP examined but was unaffected by sulindac. Phenidone did not alter the cell killing achieved by CDDP at normal temperature or when the CDDP was followed by local hyperthermia, but use of a combination of sulindac or diflunisal plus phenidone increased the cell killing achieved by 2-10-fold when used with local hyperthermia over the dose range of CDDP tested. In tumor growth delay (TGD) studies, addition of five daily injections of sulindac, diflunisal or phenidone did not increase the TGD achieved by CDDP at normal temperature and neither diflunisal nor phenidone markedly increased the TGD produced by CDDP in conjunction with local hyperthermia, but the administration of sulindac resulted in about a 3-fold increase in TGD as did use of a combination of diflunisal or sulindac plus phenidone. These results indicate that inhibitors of arachidonic acid metabolism can increase the cell killing and the tumor growth delay produced by CDDP plus local hyperthermia.     

Aromatase inhibitor development for treatment of breast cancer

Summary Inhibition of estrogen production provides effective therapy for patients with hormone-dependent breast cancer. The source of estrogens in premenopausal women is predominantly the ovary, but after the menopause, estradiol is synthesized in peripheral tissues through the aromatization of androgens to estrogens. Uptake from plasma is the primary mechanism for maintenance of estradiol concentrations in breast cancer tissue in premenopausal women, whereas several steps may be operant in postmenopausal women. These include enzymatic synthesis of estradiol via sulfatase, aromatase, and 17-hydroxysteroid dehydrogenase in the tumor itself. Aromatization of androgens secreted by the adrenal to estrogens in peripheral tissues and transport to the tumor via circulation in the plasma provides another means of maintaining breast tumor estradiol levels in postmenopausal women. These various sources contribute to the high tissue estrogen levels measured in breast tumor tissue.To effectively suppress tissue concentrations of estrogens and circulating estradiol in postmenopausal patients, various aromatase inhibitors have been developed recently. These include steroidal inhibitors such as 4-hydroxy-androstenedione as well as non-steroidal compounds with imidazole and triazole structures. The most potent of these, CGS 20267, is reported to suppress levels of active estrogens (i.e., estrone, estrone sulfatase, and estradiol) by more than 95%. This compound can suppress both serum and 24-hrurine estrogens to a greater extent than produced by the second generation inhibitor, CGS 16949A. CGS 20267 is highly specific since it does not affect cortisol and aldosterone serum levels during ACTH stimulation tests nor sodium and potassium balance in 24-hr urine samples. These data suggest that CGS 20267 can be expected to bring improved response rates in the treatment of metastatic hormone-dependent breast cancer without substantial side effects.Presented by R.J. Santen at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, November 4, 1993; Mini-symposium on New Agents in Breast Cancer (supported by an educational grant from Rhône-Poulenc Rorer).     

Effect of probenecid on the formation and elimination kinetics of the sulphate and glucuronide conjugates of diflunisal

The effect of probenecid on the pharmacokinetics of diflunisal and its glucuronide and sulphate conjugates was studied in 8 healthy volunteers. Diflunisal 250 mg b. d. was administered p. o. for 15 days and its steady state pharmacokinetics was evaluated on Day 16 after the last dose (control phase). Probenecid 500 mg b. d. was co-administered throughout the entire study period in the treatment phase of the study.The steady state plasma concentration of diflunisal was significantly higher during the probenecid treatment phase as compared to the control phase (104.0 vs. 63.1 g·ml^–1). This was the result of a significant decrease in the plasma clearance of diflunisal from 5.8 (control) to 3.4 ml·min^–1 (probenecid co-administration). The metabolite formation clearances of both glucuronides were significantly decreased by probenecid, -45 % and -54 % for the phenolic and acyl glucuronide, respectively. The metabolite formation clearance of the sulphate conjugate was not affected by probenecid co-administration.Steady state plasma concentrations of the sulphate and glucuronide conjugates of diflunisal were 2.5- to 3.1-fold higher during probenecid co-administration, due to a significant reduction in the renal clearance of the three diflunisal conjugates. Probenecid also reduced the plasma protein binding of diflunisal, but only to a minor extent; the unbound plasma fraction of diflunisal at steady state averaged between 5 and 30 % higher during probenecid co-administration.     

Mortality among homeless shelter residents in New York City

OBJECTIVES: This study examined the rates and predictors of mortality among sheltered homeless men and women in New York City. METHODS: Identifying data on a representative sample of shelter residents surveyed in 1987 were matched against national mortality records for 1987 through 1994. Standardized mortality ratios were computed to compare death rates among homeless people with those of the general US and New York City populations. Logistic regression analysis was used to examine predictors of mortality within the homeless sample. RESULTS: Age-adjusted death rates of homeless men and women were 4 times those of the general US population and 2 to 3 times those of the general population of New York City. Among homeless men, prior use of injectable drugs, incarceration, and chronic homelessness increased the likelihood of death. CONCLUSIONS: For homeless shelter users, chronic homelessness itself compounds the high risk of death associated with disease/disability and intravenous drug use. Interventions must address not only the health conditions of the homeless but also the societal conditions that perpetuate homelessness.     

The effect of congenital anomalies on mortality risk in white and black infants.

OBJECTIVES: This population-based study examined the effect of all major congenital anomalies on the mortality of White and Black infants by infant sex, birthweight, gestational age, and lethality of the anomaly. The study also determined the total contribution of anomalies to infant mortality. METHODS: California Birth Defects Monitoring Program data were merged with linked birth-death files for 278,646 singleton non-Hispanic White and Black infants born in 1983 through 1986. Malformed infants were compared with nonmalformed infants to determine the effect of anomalies on mortality. RESULTS: The presence of any congenital anomaly increased mortality 9.0-fold (95% CI = 7.3, 11.1) for Black infants and 17.8-fold (95% CI = 16.2, 19.6) for White infants. Even "non-lethal" anomalies increased mortality up to 8.9-fold. Overall, anomalies contributed to 33% of White infant deaths, to 19% of Black infant deaths, and to over 60% of deaths among Black and White neonates weighing over 1499 g. CONCLUSIONS: The contribution of congenital anomalies to mortality of both low- (< 2500 g) and normal-birth-weight infants is substantially higher than previously estimated, representing a large public health problem for both Black and White infants.     

Can nuchal cord cause transient increased nuchal translucency thickness?

When detected in a first trimester scan, an increased thickness of nuchal translucency (NT) may be associated with chromosomal, cardiac or genetic disorders. However, less attention has been devoted to the outcome of those fetuses who have confirmed normal anatomies and karyotyping, but have abnormal first trimester scans. Thus, a challenging new issue is how to counsel such cases of transient increased NT in which the translucency rapidly vanishes with no evidence of other underlying abnormalities. Two cases of transient increased thickness of NT are reported. In both, a nuchal cord was ultrasonographically demonstrated and a thorough work-up revealed chromosomally and anatomically normal fetuses. The pathophysiological theories behind these observations and their significance are discussed. Based on these observations, we suggest that transvaginal sonography combined with Doppler flow studies should be utilized for the presize detection of cord patterns to accomplish the work-up in cases of increased NT.