Improved bioavailability and clinical response in patients with chronic liver disease following the administration of a spironolactone: β-cyclodextrin complex

Aims To compare the absorption and clinical effect of spironolactone from an inclusion complex with β-cyclodextrin (SP-COMP) to Aldactone tablets (ALD) in chronic liver disease.
Methods Patients, admitted with chronic liver disease, completed a randomized crossover steady state study. They received their spironolactone dose as either daily SP-COMP or ALD for 7 days. Serial blood samples were drawn over a 24  h period from day 7 of each therapy. Accurate fluid balance was recorded on days 5–7 and 12–14. Thirteen (six females) whose mean (s.d.) age and weight was 58.4(9.3) years and 74.3(19.0)  kg completed the study.
Results The mean (95% confidence limits) relative bioavailability for SP-COMP (compared with ALD) from steady state serum concentrations of canrenone, 6β-hydroxyl 7α-thiomethyl spironolactone and 7α-thiomethyl spironolactone was 310.0 (265.4, 336.7), 233.4(212.9, 250.8) and 254.8(230.8, 279.0)%, respectively. Improvements in clinical status and fluid balance occurred over the last 3 days of SP-COMP with a mean (s.d.) net loss, in fluid balance, of 1370(860)ml compared with a gain of 228(936)ml during ALD.
Conclusions Better absorption of spironolactone from the spironolactone: β-cyclodextrin complex formulation should lead to a reduction in dosage and perhaps a more consistent effect in patients with chronic liver disease.     

Allergic contact dermatitis from grasses

This study attempts to demonstrate the existence of allergic contact dermatitis from grass, and to develop a patch test series to screen patients with grass intolerance. 6 common grass species from lawns and military training areas were collected. Solvent extracts of polar. non-polar and volatile fractions were prepared and used for patch testing in 20 control subjects and 46 patients with a history of grass intolerance. The 20 control had negative responses to patch testing. 5 out of 46 patients had positive patch tests to Axonopus compressus (carpet grass). Ischaenmum muticum (sea-shore centipede grass). Imperata evlindrica (lalang). Panicum maximum (Guinea grass) and Pennisetum purpureum (elephant grass). Reactions to the non-polar fraction for all 5 species were noted. This study demonstrates the existence of allergic contact dermatitis from various common species of grass. In our series, this is seen in 11% of those with a history of grass intolerance.     

Fundus biomicroscopy: a comparison of four methods

Funduscopic examination utilizing the biomicroscope is extremely valuable in the detection, diagnosis, and management of ocular disease. A variety of lenses are currently available for detailed examination of the posterior vitreous cavity and the retina. This paper discusses the optical principles and the various attributes of four lenses relative to magnification, field of view, clinical application and ease of use.     

Retrovirus-induced immunodeficiency in mice exacerbates gastrointestinal candidiasis.

Dysfunction of neutrophils in patients infected with human immunodeficiency virus is at least partly responsible for secondary microbial diseases in these individuals, including invasive gastrointestinal (GI) candidiasis. Immunoregulatory disturbances associated with the development of AIDS in human immunodeficiency virus-infected patients exacerbates Candida albicans infection of the upper GI tract and frequently leads to oropharyngeal and esophageal candidiasis. In this article, we present the first report of a murine model of invasive GI candidiasis associated with an AIDS-related murine immunodeficiency syndrome that results from infection of C57BL/6 mice with a previously described retrovirus complex (LP-BM5). Mice of the inbred strain were infected with C. albicans by oral-intragastric inoculation as infants and with the retrovirus by the intraperitoneal route 30 days later. Control mice of the same strain were infected with C. albicans as above and subsequently infected with the avirulent, ecotropic helper virus (MBI-5). Animals were killed 90 days after retroviral challenge. Total and differential blood cell counts, CD4+ T-cell counts in the spleen, and the histopathology of the gastric mucosa of experimental and control animals were determined. The virulent LP-BM5-infected animals developed murine AIDS and showed eruptive and suppurative lesions, with associated C. albicans mainly in regions of the cardial-atrium fold of the stomach. Well-defined abscesses with entrapped C. albicans hyphae were observed in the region of the cardial-atrium fold of control mice. A significant increase in the number of C. albicans CFU in homogenized and plated segments of the GI tract was recognized in mice with murine AIDS versus the control animals. The murine model of GI candidiasis reported here permits examination of the nature of C. albicans interaction with the gastric mucosa both in the immunocompetent host under conditions in which the yeast exists predominantly as a commensal organism and in the immunosuppressed host during progressive stages of AIDS induced by a retroviral infection.     

Biphasic response of clonidine in isolated rat aortae.

Clonidine as a partial agonist of alpha adrenoceptor in Wistar rat aorta has been documented. It was however observed that the effect of clonidine on the isolated rat aorta of Sprague Dawley rats was slightly different. The concentration effect curve induced by clonidine was on the right of that induced by phenylephrine, with EC50 of 1.5 x 10(-7) M and 3.5 x 10(-4) M for the phenylephrine- and clonidine-induced responses, respectively; but the maximal contraction induced by clonidine was similar to that of phenylephrine. In the presence of clonidine, the concentration effect curve of phenylephrine was shifted to the right. Both the phenylephrine- and clonidine-induced contraction were inhibited by prazosin, and the EC50 values for prazosin in phenylephrine- and clonidine-induced contraction were 1.0 x 10(-8) M and 1.8 x 10(-6) M, respectively. Yohimbine in concentration sufficient to antagonize almost completely the effect of phenylephrine was found to slightly prevent the effects of clonidine. Further increase of clonidine above 2 x 10(-3) M, the concentration sufficient to induce the maximal contraction, however induced depression of the clonidine-induced contraction, and this phenomenon was concentration dependent. Possible explanation of this phenomenon was discussed.     

Different effects of intracellular and extracellular TEA on voltage-dependent K currents of acutely isolated hippocampal CA1 neurons.

Tetraethylammonium (TEA) effects on K currents were examined on either side of the membrane of hippocampal CA1 neurons by means of whole-cell voltage-clamp recording and intracellular perfusion. Recording media contained ion channel blockers to allow the selective activation of voltage-dependent K currents which consisted of a rapidly decaying component (A-current) and a delayed component. Voltage protocols were applied to separate the A-current from the delayed component. Results show that 10 mM extracellular TEA suppressed 50 +/- 11% (S.D., n = 4) of the delayed current at different levels of depolarization but had little effect on the A-current. In contrast 10 mM TEA applied by intracellular perfusion suppressed the A-current by 42 +/- 10% (S.D., n = 4) in addition to inhibiting the delayed currently 55 +/- 15% (S.D., n = 4). Both the intracellular and extracellular actions of TEA on K currents showed no voltage- nor time-dependency. The results suggest that voltage-dependent transient current (A-current) is mediated through a separate group of ionic channels distinct from those that sustained the delayed current. Furthermore, the asymmetrical effects of intracellular and extracellular TEA on the transient current are similar to those described for the A-current in molluscan neurons. This observation supports the notion that the structure of the ion channel mediating the A-current is closely conserved across different species.     

Abdominoperineal resection for adenocarcinoma of the low rectum

Current understanding of the routes of spread of rectal cancer along with technical innovations such as the circular stapler have allowed surgeons to treat most rectal cancers with an anterior resection and low anastomosis. Appropriate use of local therapy options has further decreased the need for abdominoperineal resection (APR). Nonetheless, APR remains the procedure of choice for many distal rectal adenocarcinomas. Numerous factors influence the decision to perform an APR and are discussed in detail. Although mortality for APR has been reduced significantly, morbidity remains high. Specific complications commonly seen after APR are discussed. Operative technique is outlined since much of the specific morbidity of APR can be reduced by attention to detail in the conduct of this complex procedure.

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Resumen El conocimiente actual de las rutas de extensión del cáncer rectal junto con innovaciones técnicas tales como el suturador circular han permitido a los cirujanos tratar la mayoría de los cánceres rectales mediante la resección anterior con anastomosis baja. El uso apropiado de opciones de tratamiento local ha disminuido aún más la necesidad de practicar la resección abdominoperineal (RAP). Sin embargo, la RAP sigue siendo el procedimiento de escogencia para muchos adenocarcinomas del recto distal. Son numerosos los factores que influyen sobre la decisión de realizar una RAP y éstos son motivo de discusión detallada en el presente artículo. Aunque la mortalidad asociada con la RAP se ha reducido significativamente, la morbilidad se mantiene elevada. Se revisan las complicaciones específicas más comunes después de la RAP. Se detalla la técnica quirúrgica, puesto que mucha de la morbilidad específica de la RAP puede ser disminuida si se presta especial atención al detalle en la ejecución de este complejo procedimiento.

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Résumé La connaissance récente des voies de dissémination lymphatique du cancer du rectum ainsi que les innovations techniques comme la machine à agraphage mécanique ont permis de traiter la plupart des tumeurs rectales par une résection antérieure et une anastomose basse. L'utilisation de la radiothérapie locale a diminué encore les indications d'amputations abdomino-périneales. Néanmoins, l'amputation reste l'indication de choix dans beaucoup de cancers rectaux distaux; les facteurs qui interviennent dans ce choix sont discutés. Bien que la mortalité des amputations abdomino-périneales ait beaucoup diminuée, la morbidité reste élevée. Les complications spécifiques de l'amputation sont exposées. La technique opératoire est exposée parce que la morbidité peut être souvent réduite lorsque le chirurgien fait attention à tous les détails au cours de cette intervention complexe.

     

Influence of socioeconomic status on cardiovascular diseases in Hong Kong.

STUDY OBJECTIVE--The aim was to explore the relationships between five socioeconomic variables and three main cardiovascular diseases (ischaemic heart disease, hypertensive disease, and cerebrovascular disease) in Hong Kong. DESIGN--This cross sectional study used data from the 1986 by-census and registered death data for 1985 to 1987 in Hong Kong. For each of 24 districts, the correlation coefficients between log standardised mortality ratios for the three cardiovascular diseases and the percentages of professional and administrative workers, production and agricultural workers, persons aged 15 and over having tertiary education, households with higher income, and people living in private residential blocks were calculated. Besides simple linear regression and correlation, factor analysis was used to produce a new single surrogate measure summarising the five most useful variables in 24 sets of districts. SETTING--The whole Hong Kong area (population approximately 5.5 million) was divided into 24 districts, which were the study units. MEASUREMENTS AND MAIN RESULTS--For ischaemic heart disease in men, the correlation coefficients of the log standardised mortality ratios with the five socioeconomic variables as well as with the factor score were all statistically significant. For women, statistical significance was obtained in only two of five socioeconomic variables. No such trends were obtained for the other two cardiovascular diseases for either men or women. CONCLUSIONS--The study suggests that in Hong Kong in recent years, a higher level of socioeconomic status is associated with higher risk of death from ischaemic heart disease; but this association is not present for hypertensive disease and cerebrovascular disease.     

In vivo production of tumor necrosis factor for the treatment of mice bearing Ehrlich ascites tumor.

Tumor necrosis factor (TNF) was produced in mice bearing Ehrlich ascites tumor (EAT) by priming with zymosan and subsequently challenging with lipopolysaccharide. The optimal conditions for the in vivo production of TNF in treating EAT bearing mice were established. The endotoxin shock induced in mice during TNF production could be minimized by the combined administration of sulindac and mannoheptulose. The endogenous TNF produced could suppress proliferation of EAT cells as well as prolong the survival time of mice bearing small tumors.