Systematic variations in immune response-related gene transcript abundance suggest new questions about environmental influences on lacrimal gland immunoregulation.

PURPOSE: Retrospective analyses were undertaken to assess the hypothesis that environmental variables influenced immunophysiological status of lacrimal glands from untreated female rabbits that had been housed out-of-doors until they were acquired for use as controls for experimental studies. MATERIALS AND METHODS: Rabbits were euthanized within 5 days of arrival at University Vivaria. Glands were divided for histology and RNA extraction. Transcript abundances were determined with real time RT-PCR. Sections were stained for CD18 and rabbit thymic lymphocyte antigen. Environmental variables assessed were mean daily high temperature, low humidity, high temperature/low humidity ratio, and days with above average temperature/humidity ratio ("adverse days") during the prior 30 days. RESULTS: Spearman's analyses revealed numerous significant correlations. Numbers of T cells and abundances of mRNAs for CD8; CCL2, and CCL4; IL-1α and IL-1ß; the T(H)1 cytokine, IL-2; and the T(H)2- and B cell cytokines, IL-4, IL-6, IL-10, APRIL, and BAFF, all increased with adverse days, while IFN-γ mRNA abundance decreased. Glands from the group exposed to the most adverse days remained free of immunopathological lesions. Glands from the group exposed to the highest temperatures fell above the regression curves for IL-4, APRIL, and BAFF calculated for the other groups and had significantly higher abundances of mRNAs for prolactin, IL-18, CCL21, CCL28, CXCL8, and CXCL13. One of six glands from this group contained small immune cell aggregates; the others appeared normal. The only gland that presented with frank histopathology was from a group that had experienced benign conditions. CONCLUSIONS: Increasing adverse days correlated with increasing abundances of transcripts, including mRNAs for IL-2, IL-10, and CD8, outside the T(H)1/T(H)2 paradigm. The findings raise intriguing questions as to whether and how such changes might be associated with homeostatic phenomena.

Autoimmune dacryoadenitis and keratoconjunctivitis induced in rabbits by subcutaneous injection of autologous lymphocytes activated ex vivo against lacrimal antigens.

Autologous peripheral blood lymphocytes (PBL), activated in a mixed cell reaction when co-cultured with purified rabbit lacrimal epithelial cells, are known to induce a Sjögren's-like autoimmune dacryoadenitis and keratoconjunctivitis when injected directly back into the donor animal's inferior lacrimal gland (LG). This study shows that autoreactive lymphocytes injected subcutaneously in a site away from the LG is capable of inducing an autoimmune disease in a rabbit. Induced disease (ID) develops more slowly, taking 4weeks as compared to 2weeks in the direct injection model. Initially, both clinical symptoms and histopathology are less pronounced than in the direct injection ID model, but later the immunocytochemistry shows the same CD4+/CD8+ ratio of 4:1 for both injection methods. The finding that lymphocytes activated against lacrimal antigens can travel or home from the injection site back to the inferior and superior LG, as well as the conjunctiva, suggests that these anatomical sites may have common epitopes that induce pathogenic CD4+ T cells that produce a Sjögren's-like syndrome.

Effect of propranolol on the QT intervals of normal individuals during exercise: a new method for studying interventions.

A new method was used to study the effect of a single dose of propranolol on the QT intervals during exercise in 11 normal volunteers. They exercised maximally on a bicycle ergometer and repeated the test after taking propranolol (40 mg) by mouth two hours before. Electrocardiograms were continuously recorded on magnetic tape and the cardiac cycle length (RR interval) and the QT interval were measured every five seconds by a computer aided method. The RR-QT data from each test during the exercise phase were analysed by an exponential formula, QT = A - B x exp (-k x RR) and by Bazett's formula, QT = K x square root of (RR). Three reference QT intervals, QTc1, QTc2, and QTc3, estimated at RR = 400, 700, and 1000 ms respectively from the regression curves of both formulas were compared. The exponential formula, which consistently gave a better fit with the data, showed that propranolol had a biphasic action on the QT intervals during exercise. It significantly prolonged the mean (SD) interval at longer cycle lengths (from 287 (27) to 305 (18) ms at RR = 1000 ms and shortened it at shorter cycle lengths (from 198 (14) to 179 (16) ms at RR = 400 ms). In contrast, Bazett's formula did not show any significant effect when the same raw data were used. The exponential formula can be adapted to study other interventions or conditions that affect QT intervals.

The small right coronary artery: angiographic implications--case reports.

Two patients with small right coronary arteries are presented. Possible complications during coronary angiography and methods of preventing them are discussed. It is stressed that the time of occlusion of the artery by the catheter tip should be kept to a minimum. The use of newly available angiographic catheters with side holes is also illustrated.

Effect of ethanol on regional myocardial blood flow and hemodynamics, before and after coronary artery ligation in dogs.

The effects on regional myocardial blood flows (RMBF) and hemodynamics due to ethanol administered before and after acute coronary artery ligation (CAL) in 18 anesthetized dogs were studied. Ethanol was administered to seven dogs (group I) prior to CAL and to six dogs (group II) after CAL; five dogs (group III, control) received only saline before and after CAL. Uniform blood ethanol levels (180 +/- 30 mg/dl) were maintained in groups I and II after initial ethanol administration. In these groups the heart rate and rate-pressure product (which reflects myocardial oxygen consumption) remained stable, but pulmonary arterial pressures were elevated. Other hemodynamic parameters remained stable in all groups. Ethanol caused a significant transmural increase of RMBF (p less than 0.001) in both groups I and II. In group II the increase was significant in both nonischemic and ischemic tissues, with no apparent redistribution of flow among the myocardial layers. The percentage increase of RMBF due to ethanol was highest in group II nonischemic tissue (95-107%) compared to the corresponding ischemic tissue (57-60%) and the group I myocardial tissue (36-47%) prior to CAL (p less than 0.001). The observed differences between ethanol pre- and posttreatments suggest different interactions between ethanol and catecholamines. The results also confirm that vasodilatory reserve is present in the acutely ischemic myocardium and that the local availability of ethanol is important for coronary vasodilatation.

Hysteresis in the human RR-QT relationship during exercise and recovery.

The present study was undertaken to test the hypothesis that the human RR-QT relationship during dynamic exercise differs markedly from that during the recovery phase. Fourteen subjects from the age of 16 to 71 years exercised on a treadmill according to the Bruce protocol. Electrocardiograms were recorded continuously on a magnetic tape, from 1 minute before exercise to 10 minutes into recovery. An exponential formula, proposed by us earlier, closely represented the exercise RR-QT data. However, it was not appropriate for the often S-shaped recovery curves which invariably deviated from the exercise curves, exhibiting hysteresis. Initially, all recovery QT intervals were shorter than the exercise values, but later in the recovery, some crossed the exercise curves from below, resulting in longer QT intervals. The recovery data were fitted by a third degree polynomial, and the hysteresis was calculated as the area between the exercise and recovery curves within a 150 ms range of the RR interval starting from its minimum value. The mechanisms for the occurrence of hysteresis are likely to involve the sympatho-adrenal activity in the early post-exercise period and the time course of QT interval adaptation to rapid changes in the RR interval.

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

The effects of the calcium antagonist diltiazem on diastolic blood pressure and various parameters of erythrocyte membrane cation transport were evaluated in hypertensive patients with diastolic blood pressure between 95 and 110 mm Hg in a placebo-controlled, double-blind parallel study. Twenty-one patients completed the study; 13 received placebo, while 8 received diltiazem. Diastolic blood pressure, intracellular sodium and calcium concentrations, ouabain-sensitive Na+,K+-adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across red blood cell membranes were examined in both groups at the end of placebo run-in, at the end of the titration phase, and at the completion of study. In the placebo group, none of the parameters changed significantly. In the drug-treated group, diastolic blood pressure declined by approximately 10% (placebo, 95.1 +/- 8.9; drug-treated, 86.9 +/- 4.9 mm Hg; p less than 0.03) at the end of the study. There were also reductions in intracellular sodium (placebo, 7.9 +/- 1.8; drug-treated, 5.2 +/- 0.4 mmol/L cells; p less than 0.002) and calcium (placebo, 13.5 +/- 1.6; drug-treated 10.8 +/- 3.3 mumol/L cells; p less than 0.03) concentrations, accompanied by a simultaneous rise in the activity of the ouabain-sensitive Na+,K+-ATPase of erythrocyte membranes (placebo, 7.1 +/- 1.1 X 10(-2); drug-treated, 9.0 +/- 0.6 X 10(-2) microM inorganic phosphate/hr/mg; p less than 0.001) at the end of the study. However, no significant change in the ouabain-insensitive moiety of the ATPase pump was found. Diltiazem treatment increased net sodium efflux and potassium influx.(ABSTRACT TRUNCATED AT 250 WORDS)

Knotting of a bypass graft catheter: report of a case.

A case of knotting of a bypass graft catheter during coronary arteriography is presented. An arteriotomy had to be done to remove the catheter. A possible mechanism causing this complication and precautions to avoid it are described.

Diltiazem as monotherapy for systemic hypertension: a multicenter, randomized, placebo-controlled trial.

A multicenter, randomized, placebo-controlled, parallel group study of diltiazem in essential hypertension was carried out in 77 patients (40 diltiazem, 37 placebo) with stable supine diastolic blood pressure (BP) between 95 and 110 mm Hg. Patients were withdrawn from previous antihypertensive therapy for at least 4 weeks, titrated to the optimal dose, and followed for a total of 12 weeks during therapy. A diltiazem dose of 360 mg/day was required in 85% of the patients. Average BP in all positions was significantly (p less than 0.0001) reduced by diltiazem compared with placebo. With diltiazem, average supine BP fell from 156/100 mm Hg at baseline to 141/87 at end titration and 145/90 mm Hg at week 12, whereas average standing BP fell from 152/101 mm Hg to 136/90 and 143/91 mm Hg, respectively, at those times. There was no significant change in heart rate at week 12. Diltiazem tended to be more effective in older patients, but caused no increase in orthostatic BP drop. There were no statistically significant changes in BP in the placebo group. Two patients receiving placebo and 1 patient receiving diltiazem discontinued therapy as a result of adverse effects, and overall, side effects were only slightly more common with diltiazem treatment. Thus, diltiazem was effective and well tolerated single therapy for mild to moderate systemic hypertension and appears to compare favorably to most agents being used.

Longterm complications of Beall prosthetic valve: a case report.

A case of malfunctioning Beall prosthetic mitral valve causing severe heart failure is presented. The unusual aspect of this malfunction was the finding of disc dislodgment despite the absence of pathology in the disc itself. The dislodgment was caused by excessive tissue ingrowth around the suture ring. The need for close clinical follow-up of this type of prosthetic valve is emphasized.