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.     

Causes of Alcoholism: A Qualitative Study of Traditional Muscogee (Creek) Indians

Abstract Traditional Native American people are experiencing serious health, economic, and social problems resulting from alcoholism. Native Americans maintain a worldview of health and illness that conflicts with the dominant culture's approach to treatment. The purposes of this study were to describe the health beliefs of traditional Muscogee (Creek) Indians concerning the causes of illness and learn how these beliefs relate to alcoholism. The researchers conducted in-depth interviews of 55 traditional Muscogee (Creek) participants to learn traditional beliefs about illness and alcoholism. Data were analyzed using content analysis. Results indicate that both illness and alcoholism are perceived as having natural and unnatural (supernatural) causes. A challenge facing nurses is how to provide culturally sensitive care when clients' and nurses' beliefs about the cause of alcoholism may be in conflict. The authors discuss preservation, accommodation, and repatterning of health care beliefs as a basis for planning culturally sensitive nursing care.     

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.     

Orthostatic blood pressure control and ageing*

Reflex haemodynamic responses to orthostatic stress are attenuated with ageing, the extent of attenuation increasing with advancing age. In 15–20% of individuals aged >65 years, the attenuation may be so marked that there is an excessive fall of blood pressure (BP) on assumption of the upright posture, sufficient on occasions to cause symptomatic cerebral hypoperfusion - this is known as ‘ageing-related’ orthostatic hypotension (AOH), a major risk factor for morbidity and mortality. Comparison of the cardiovascular responses to a variety of physiological and pharmacological stresses in healthy young and elderly subjects and in those with AOH suggests that the predominant site of the ageing-related change in cardiovascular reflex function is in the central connections of the arterial baroreflex, affecting particularly the BP buffering response. There is no evidence for ageing-related impairment of the efferent limb of the baroreflex, i. e. there is no significant ageing change in sympathetic vasomotor function or cardiac drive. Ageing-related impairment of baroreflex function also does not appear to result from either attenuation of arterial compliance or the presence of systolic hypertension, despite the epidemiological association between systolic hypertension and AOH. Better understanding of this important problem has the potential to improve the health of all elderly people.     

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.     

Psychological, biological and health behavior predictors of blood pressure changes in middle-aged women.

A long-standing hypothesis is that feelings of anger and anxiety increase the risk for essential hypertension. Most studies examining this hypothesis have been cross-sectional in design or undertaken with men only. We tested this hypothesis along with determination of the other behavioral and biological predictors of increases in systolic (SBP) and diastolic (DBP) blood pressure from baseline to a follow-up examination 3 years later in a prospective study of 468 middle-aged women whose blood pressure at the baseline examination was less than 140/90 mmHg. Analyses showed that increases in the Spielberger Trait Anger Scale between the baseline and 3-year follow-up examination, as well as Framingham Tension scores (a measure of anxiety) at baseline, independently predicted an increase in SBP (P less than 0.01). Other factors that independently predicted an increase in SBP were baseline fasting insulin, parental history of hypertension and increases in body mass index and in alcohol intake across the 3 years of follow-up. Increases in the Spielberger Trait Anger Scores independently predicted increases in DBP (P less than 0.02), as did black race, increases in body mass index and hematocrit and decreases in potassium intake. Although menopausal status and hormone replacement therapy were unrelated to changes in blood pressure, postmenopausal women on hormone replacement therapy did show significant increases in DBP in the univariate analysis. Anxiety at baseline, along with parental history of hypertension, baseline fasting insulin and baseline body mass index, predicted a later onset of hypertension, i.e. on pharmacologic treatment for hypertension, in the univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.