Reactive hyperreninemia is a major determinant of plasma angiotensin II during ACE inhibition.

The new ACE inhibitor trandolapril was administered to normal volunteers at daily doses of 0.5, 2, and 8 mg for 10 days. Twenty-one volunteers, aged 21-30 years, were included in the study. To randomly selected groups of seven subjects, each dose was administered in a single-blind fashion. None of the doses induced a consistent fall in blood pressure. Angiotensin-converting enzyme activity (ACE) was measured in vitro using three different synthetic substrates (i.e., Hip-Gly-Gly, Z-Phe-His-Leu, or angiotensin I). Although the degree of ACE inhibition assessed with the three methods varied widely, all methods clearly indicated dose-dependent ACE inhibition. These in vitro results were confirmed by measuring ACE inhibition in vivo using the ratio of plasma angiotensin II (ANG II) to blood angiotensin I (ANG I). The dose-dependent ACE inhibition was paralleled by a dose-dependent rise in active renin and blood angiotensin I levels, most evident on day 10. In contrast, plasma ANG II levels on day 10 were not different whether the volunteers received 0.5 or 8 mg trandolapril. Thus, whereas increasing doses of this new ACE inhibitor progressively enhanced the blockade of ACE activity, this was not reflected by additional reductions of plasma ANG II levels. The progressive enhancement of ACE inhibition seemed to be offset by the accentuation of the compensatory rise in renin and ANG I, which was still partially converted to ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nonmalignant monoclonal immunoglobulinemia, pernicious anemia and gastric carcinoma. A model of immunologic dysfunction: Report of two cases and review of the literature

The association of an autoimmune disease with a monoclonal immunoglobulin is not exceptional and most probably results from a dysfunction of the immunologic apparatus.This study describes two patients with monoclonal immunoglobulin A (IgA) and M (IgM) gammopathy, respectively, in whom pernicious anemia and finally gastric carcinoma developed. One patient had autoantibodies to gastric parietal cell and to thyroid microsomal antigen which could not be identified with the M-component. This observation, together with the fact that pernicious anemia occurred in one case before and in the other case after the discovery of M-component, suggests that different clones of cells were responsible for both disorders. Sixteen cases in which the patients had the same association have been collected from the literature and the data are compared with ours.     

The effect of blue light exposure and use of intraocular lenses on human uveal melanoma cell lines

Little is known about the effect of blue light on inducing melanocytic malignant transformation. We chose to investigate the effect of blue light (475 nm wavelength) on the proliferation rates of uveal melanoma cells. In addition, we tested two different intraocular lenses to determine the possible effects of ultraviolet absorbing and blue light filtering intraocular lenses on the changes in proliferation. Four human uveal melanoma cell lines (92.1, MKT-BR, OCM-1, SP6.5) were exposed to blue light with and without the presence of ultraviolet absorbing and blue light filtering intraocular lenses. Cells covered by aluminum foil were used as a control. The proliferation rate of the cells compared with the control was then assessed using the Sulforhodamine-B proliferation assay. Cells exposed to blue light showed a statistically significant (P<0.05) increase in proliferation. Those exposed to blue light through a standard ultraviolet absorbing intraocular lens showed a smaller increase in proliferation, whereas those exposed with a blue light filtering intraocular lens showed no increase in proliferation than the control in all four cell lines. The exposure of cells to blue light led to an increase in proliferation in all cell lines compared with the control. The use of blue light filtering intraocular lenses abolished these increases in proliferation in the four cell lines. These results indicate that blue light filtering intraocular lenses may have a protective effect on the proliferation rates of uveal melanoma cells exposed to blue light.     

Cost considerations of the new fixed combinations for glaucoma medical therapy

OBJECTIVE: To compare the costs of the new fixed combinations for glaucoma medical therapy. METHODS: The studied drugs were: Cosopt (5-mL bottle), Combigan (5-mL bottle) and Xalacom (2.5-mL bottle). Five bottles of each drug were obtained from pharmacies, and the medications lot numbers were recorded. To calculate the drop volume, 10 drops and 1 mL of each bottle were weighed with a digital precision scale. Drop volume was calculated by the relation between volume and weight. The cost of each bottle of medication was determined from the average retail price in Canada. The prices were obtained in Canadian dollars (dollars). RESULTS: The drops of Cosopt (39.60 +/- 0.45 microL) were considerably larger than the drops of Combigan (33.75 +/- 0.60 microL) and Xalacom (30.87 +/- 0.37 microL). The average number of drops per millilitre varied from 25.25 +/- 0.29 (Cosopt) to 32.40 +/- 0.39 microL (Xalacom). Combigan presented the lowest daily cost (dollars 0.87 +/- 0.02) followed by Xalacom (dollars 1.09 +/- 0.01) and Cosopt (dollars 1.22 +/- 0.01). The average cost by year varied from dollars 316.75 +/- 5.59 (Combigan) to dollars 445.96 +/- 5.16 (Cosopt), with a total difference of dollars 129.21 per year of treatment. CONCLUSIONS: There was a statistically significant difference in average drop size and cost among the three studied drugs. Combigan presented the lowest daily cost followed by Xalacom and Cosopt.     

Orbital metastasis of urinary bladder carcinoma: a clinicopathologic report and review of the literature

A 53-year-old male presented with a progressive mass of the left orbit. His medical history included an invasive carcinoma of the bladder diagnosed three weeks earlier. An orbital biopsy was performed and the diagnosis was that of an orbital metastasis of urinary bladder carcinoma. The patient developed widespread metastatic disease and unfortunately died one month after the diagnosis of orbital metastasis. Orbital metastasis of urinary bladder carcinoma is associated with a poor prognosis and is more frequently observed in older people. In addition, it is five times more prevalent in men than in women.     

The future of angiotensin II inhibition in cardiovascular medicine

Drugs, which interfere with the renin-angiotensin-aldosterone cascade such as angiotensin converting enzyme (ACE) inhibitors, have been available to clinicians for more than 20 years. They are now recognized as a very effective approach to treat patients with hypertension, heart failure, diabetic and non-diabetic chronic renal failure or patients with a high cardiovascular risk. The recent development of angiotensin II (Ang II) receptor antagonist has enabled to improve significantly the tolerability profile of this group of drugs while maintaining a high clinical efficacy. Yet, with the availability of Ang II receptor antagonists, new questions have arisen. Is it still possible to gain in efficacy with newer agents? What is the future of drugs such as neutral endopeptidase (NEP)/ACE inhibitors or renin inhibitors? The first objective of this review is to discuss the clinical implications of several large clinical trials that have been published recently with ACE inhibitors and Ang II receptor antagonists such as ALLHAT, LIFE, OPTIMAAL, Val-Heft, SCOPE, and more recently, CHARM, VALIANT and VALUE. With these trials, we can now define more precisely the role of these blockers of the renin-angiotensin system in the management of patients with cardiovascular complications. The second part of this review is devoted to new drugs interfering with the renin-angiotensin system. We discuss the recent results obtained with NEP/ACE inhibitors also named vasopeptidase inhibitors. Several compounds were or are in development but the experience with omapatrilat has blunted the enthusiasms for these compounds. Yet, vasopeptidase inhibitors remain very effective antihypertensive drugs and there is a great therapeutic potential for these agents provided one can define more accurately the risk/benefit ratio and the clinical indications. Finally, we present the recent data obtained with SPP 100, a new renin inhibitor that is actually under clinical development. SPP 100 has a sufficient bioavailability to induce a sustained blockade of the renin-angiotensin system when given orally to normal subjects. Recent studies have shown that SPP 100 lowers blood pressure in hypertensive patients as effectively as an Ang II receptor antagonist.     

Eyelid swelling as the only manifestation of ocular sarcoidosis

PURPOSE: To describe a case of eyelid sarcoidosis without systemic manifestations with a three-year follow-up. METHODS: A 73-year-old woman presented complaining of a one-year history of swelling and hyperemia in the right upper eyelid. To confirm the diagnosis, we performed an incisional biopsy of the eyelid. RESULTS: Histopathological examination showed a non-caseating granulomatous process suggestive of sarcoidosis. After three years, the patient was asymptomatic and physical and laboratory examination showed no signs of systemic sarcoidosis. CONCLUSION: The histopathological exam was fundamental for the diagnosis.     

Role of the growth arrest-specific gene 6 (gas6) product in thrombus stabilization

Growth arrest-specific gene 6 (gas6) product enhances the formation of stable platelet macroaggregates in response to various agonists. To determine whether Gas6 amplifies the response to known platelet agonists through one or more of its receptor tyrosine kinases of the Tyro3 family, mice deficient in any one of the Gas6 receptors (Gas6-Rs: Tyro3, Axl, or Mer) were submitted to thrombosis challenge and their platelet function. The loss of any one of the Gas6-Rs protects mice against thromboembolism induced by collagen-epinephrine and stasis-induced thrombosis. Importantly, these mice do not suffer spontaneous bleeding and have a normal bleeding time but a tendency to repetitively re-bleed after transient hemostasis. Re-bleeding in mice lacking any one of the Gas6-Rs is not due to thrombocytopenia or coagulopathy but to a platelet dysfunction characterized by a lack of the second wave of platelet aggregation and an impaired clot retraction, at least in part by reducing outside-in alpha(IIb)beta(3) signaling and platelet granule secretion. The early release of Gas6 by agonists perpetuates platelet activation through its three receptors, reinforcing outside-in alpha(IIb)beta(3) signaling by activation of PI3K and Akt signaling and stimulation of tyrosine phosphorylation of the beta(3) integrin. Furthermore, "trapping" Gas6 prevents pathological thrombosis, which indicates that blocking this novel cross-talk between the Gas6-Rs and alpha(IIb)beta(3) integrin may constitute a novel target for antithrombotic therapy.     

Higher intakes of energy and grain products at 4 years of age are associated with being overweight at 6 years of age

This study examined dietary factors associated with overweight in a population-based sample of 6-y-old children. Analyses of data from the Québec Longitudinal Study of Child Development (QLSCD) included a representative sample (n = 1014) of children born in 1998 in the province of Québec, Canada. Dietary intake was measured by using a 24-h dietary recall administered at 4 y of age. Weight and height were measured using a standard protocol at 6 y. Using logistic regression, higher daily energy intake at 4 y was significantly related to overweight at 6 y. After adjustment for confounding and overweight at 4 y, the relationship remained significant among girls (P = 0.04) but became marginally significant among boys (P = 0.07). Additionally, boys who consumed ≥5 servings of grain products/d at 4 y were more likely to be overweight at 6 y compared to those who did not [adjusted OR = 3.20 (95% CI): 1.72-5.97]. The association attenuated somewhat after adjustment for overweight at 4 y [OR = 1.82 (95% CI): 0.894-3.71; P = 0.09]. The findings provide support for the revisions made in the Canadian dietary guidelines for young children, which now recommend 4-7 servings of grain products daily for children aged 4-8 y rather than the excessive 5-12 servings of previous recommendations.