Spontaneous bilateral Achilles tendon rupture in a patient treated with oral levofloxacin.

A case of bilateral rupture of the Achilles tendon in a patient treated with levofloxacin for cystitis is reported. A 76-year-old woman suddenly developed painful ankles one day after levofloxacin treatment. Drug therapy was switched to amoxicillin/clavulanate on the fourth day. Sonography revealed a serious condition of tendinosis with complete bilateral full-thickness rupture on day 6. Tendons were both repaired in the same surgical session. Pathological anatomy of the specimens reported fatty tissue lobules with panniculitis and histiocytosis. Ankles were immobilized postoperatively with a plaster cast. Achilles tendon rupture may occur as an adverse side effect of short-term use of levofloxacin, a fluoroquinolone antibiotic. This adverse effect is a rare and poorly understood complication of this antibiotic therapy. A review of the literature is provided.

Lack of polarized type 1 or type 2 cytokine profile in asymptomatic HIV-1-infected patients during a two-year bimonthly follow-up.

The production of type 1 (interferon or IFN-gamma) and type 2 (interleukin or IL-4 and IL-10) cytokines by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) obtained from asymptomatic human immunodeficiency virus-seropositive (HIV+) patients untreated with any antiviral, antibacterial or antimycotic drugs, and from healthy individuals, was evaluated by quantitative ELISA. Patients who were HIV+ were characterized by the absence of abnormal cytokine production. The level of each cytokine differed among individuals in the same group with intersubject variations greater for HIV+ patients than for healthy individuals. The longitudinal evaluation of IFN-gamma, IL-4 and IL-10 production showed intrasubject variations which were particularly marked in HIV+ patients. Accordingly, HIV+ patients and, to a lesser extent, healthy individuals were characterized by a wide spectrum of possible profiles, which were confined to type 0 phenotype. In HIV+ patients no correlation was found between each cytokine level and the number of CD4+ T cells, not even in those with a falling CD4+ T-cell count and clinical symptoms.

Contribution of CD4+, CD8+CD28+, and CD8+CD28- T cells to CD3+ lymphocyte homeostasis during the natural course of HIV-1 infection.

The relationship between the number of circulating CD4+ T cells and the presence of particular CD8+ T cell subsets was analyzed by flow cytometry on PBL from asymptomatic HIV-1-infected patients whose specimens were collected every 2 mo for a total period of 32 mo. Only slight variations were detected in the absolute number of lymphocytes and percentage of CD3+ lymphocytes, whereas both CD4+ and CD8+ T cell subsets showed wide intrapatient variation. Variations in the number of CD8+CD28+ cells paralleled those of the CD4+ T cell subset in each patient tested, while the presence of CD8+CD28- T cells correlated inversely with CD4+ and CD8+CD28+ T cells. These data show that changes in the number of circulating CD4+-and CD8+CD28+ T cells are strongly related to the presence of CD8+CD28- T cells in these patients. Insight into the significance of CD8+CD28- T cell expansion will allow us to understand the mechanisms and significance of the HIV-1- driven change in CD4+CD8+ T cell homeostasis and the basic immunopathology of HIV disease.

T cells from individuals in advanced stages of HIV-1 infection do not proliferate but express activation antigens in response to HIV-1-specific antigens.

Like T cells from healthy subjects, those of HIV-1-infected patients are capable of expressing activation antigens on their surface after antigenic or mitogenic stimulation, but their proliferative activity is strongly reduced or even absent, especially in patients with advanced stages of the disease. The characteristic of expressing activation antigens in response to different stimuli in the absence of cell proliferation is shared by CD4+ and CD8+ T-cell subsets from HIV-1-infected patients. The number of T cells capable of expressing CD25 and CD71 in response to HIV-1-related antigens but not of proliferating increased significantly with the progression of the disease, but the number of T cells capable of expressing the two activation antigens in response to the classic tetanus toxoid recall antigen decreased. The higher numbers of T cells capable of responding to HIV-1-related antigens in conjunction with a reduction in the number of T cells responding to recall antigens may explain the occurrence of different infections, including opportunistic microorganisms, during the more advanced stages of HIV-1 infection. Because the increase in the number of HIV-1 antigen-responding T cells (defined by CD25 and CD71 activation antigen expression) is a characteristic of symptomatic HIV-1-infected patients, expression (by flow cytometry) of these activation antigens on T cells in response to HIV-1 antigens could be used as a new marker of disease progression.

Characterization of T cell subsets involved in the production of IFN-gamma in asymptomatic HIV-infected patients.

Cells capable of interferon (IFN)-gamma synthesis following mitogenic stimulation can be detected and quantified by a recently developed immunofluorescence assay and flow cytometric analysis. The production of IFN-gamma was investigated in a cohort of 20 asymptomatic human immunodeficiency virus (HIV)-seropositive patients with normal numbers of CD4+ lymphocytes, and in 10 healthy subjects. About 60% of asymptomatic stage A1 patients had increased percentages of blood lymphocytes capable of IFN-gamma synthesis, as compared to healthy subjects. The difference reflected the relatively higher numbers of CD8+ cells, in particular the CD8+ T cell subset lacking CD28 antigen expression. The strong correlation between the CD4+/CD8+ ratio and the CD8+CD28+/CD8+CD28- ratio suggests either a role for CD4+ cells in controlling the CD28+ phenotype or a role for CD8+CD28- cells in the decline of CD4+ lymphocytes. The peculiar ability of CD8+CD28- cells to produce high amounts of IFN-gamma, as compared to CD8+CD28+ cells, supports the hypothesis that the CD8+CD28- lymphocytes constitute a population that is functionally distinct from their double-positive counterparts.

IFN-gamma restores HIV- and non-HIV-specific cell mediated immune response in vitro and its activity is neutralized by antibodies from patients with AIDS.

The addition of IFN-gamma to cultures of peripheral blood mononuclear cells (PBMCs) obtained from asymptomatic HIV-infected patients increased cell proliferation in response to HIV envelope synthetic peptides (Env), influenza A virus (VIRUS), and allogeneic lymphocytes (ALLO) but not to phytohaemagglutinin (PHA) stimulation. F(Ab)2 fragments of IgG purified from the sera of HIV-seropositive patients specifically interfered with IFN-gamma-induced cell proliferation in response to recall antigens. Neutralization of the lymphokine activity was found to be sustained by specific IFN-gamma antibodies. Data obtained demonstrate that IFN-gamma can restore the cell-mediated immunity of a number of asymptomatic HIV+ individuals in vitro, while IFN-gamma antibodies present in sera of patients with AIDS interfere with the activity of the lymphokine.

CD4+ and CD8+ lymphocytes of patients with AIDS synthesize increased amounts of interferon-gamma.

Individual cells capable of interferon-gamma (IFN-gamma) synthesis are easily detected by immunofluorescence and flow cytometric analysis using an anti-IFN-gamma monoclonal antibody as specific reagent. By IFN-gamma flow cytometry assay, we demonstrated that HIV-seropositive patients, starting at the early stage of viral infection, generally have an increased percentage of lymphocytes potentially able to produce IFN-gamma, compared with healthy blood donors. IFN-gamma expression in patient lymphocytes was observed to increase with the progressive stages of HIV infection, with the highest figures occurring in stage C patients. Such increased IFN-gamma expression involved both CD4+ and CD8+ T cell subsets. Most interestingly, we found patients at the same stage of HIV infection who had similar numbers of total and CD4+ lymphocytes but highly different percentages of lymphocytes potentially capable of producing IFN-gamma.

Expression of CD28 on CD8+ and CD4+ lymphocytes during HIV infection.

CD28 interaction with B7 molecules, expressed on the membranes of antigen-presenting cells, co-stimulates cytokine production, T-cell proliferation and generation of cytotoxic lymphocytes. The expression of CD28 markers on CD4+ and CD8+ lymphocytes was studied in a group of subjects at various stages of HIV infection. A reduction in the percentage of CD28-bearing CD4+ and CD8+ cell subsets was observed during the asymptomatic stage of the disease. This reduction was more pronounced in AIDS than in non-AIDS patients. At the same time, an increase in the absolute CD8+CD28- cell number (greater in stage A than in stage B and C subjects) was observed in HIV-infected patients. The finding of an altered pattern of CD28 expression on T cells might per se explain certain early defects in the cytokine pattern and in the immune response peculiar to HIV-infected patients.

Extended release felodipine in essential hypertension. Variations in blood pressure during whole-day continuous ambulatory recording.

Intraarterial blood pressure (BP) monitoring during free ambulation (Oxford technique) was carried out in 12 essential mild-to-moderate hypertensive patients undergoing 4 weeks treatment with felodipine, 10 mg given once daily in an extended release formulation. Compared to placebo, felodipine significantly reduced systolic and diastolic blood pressure throughout 24 h. The greatest reduction was observed at 10 AM, 3 h after drug administration (-32 +/- 6/-24 +/- 5 mm Hg for systolic and diastolic BP, respectively, P less than .001). Hourly BP values remained significantly lower up to and including the 24th hour during felodipine extended release treatment (-18 +/- 5/-11 +/- 3 mm Hg, P less than .001). Felodipine extended release also reduced 24 h blood pressure variability, evaluated on the standard deviation of each hourly mean (from 16.3 +/- 0.9/12.6 +/- 0.6 to 13.4 +/- 0.6/10.4 +/- 0.6 mm Hg, P less than .01). Furthermore, absolute BP values dropped significantly at the peaks of dynamic exercise (bicycle ergometer: from 248 +/- 13/123 +/- 11 to 204 +/- 24/102 +/- 13 mm Hg, P less than .001), isometric exercise (hand grip: from 232 +/- 18/133 +/- 16 to 180 +/- 20/101 +/- 16 mm Hg, P less than .001), and cold pressor test (from 229 +/- 20/127 +/- 14 to 178 +/- 22/99 +/- 15 mm Hg, P less than .001). In conclusion, felodipine extended release exerts a good antihypertensive effect which is maintained for 24 h and reduces the level of blood pressure peaks reached under different physical stresses.

[Circadian pressure variability and pressure peaks during treatment of mild to moderate essential hypertension with felodipine]. / Variabilità pressoria circadiana e picchi di pressione durante il trattamento con felodipina nell'ipertensione essenziale di grado lieve-moderato.

It is not yet known how blood pressure variability contributes to the vascular changes associated with hypertension, but 2 possibly relevant factors are mean blood pressure levels over time and pressure peaks. It has been observed that patients in whom the variability in 24-hour blood pressure is low have a lower prevalence and severity of target organ damage. We carried out a whole-day continuous intraarterial blood pressure recording (Oxford method) in 12 essential hypertensive patients after a 2-week placebo period and after a 4-week felodipine treatment, administered in an extended release formulation, 10 mg once daily at 7 am. Felodipine significantly lowered systolic and diastolic blood pressure values throughout the 24 hours (p less than 0.005 to 0.001). Also, hourly variabilities of systolic and diastolic blood pressure during whole-day monitoring were significantly reduced (p less than 0.05 to 0.001), evaluated on the basis of the hourly means of standard deviation of systolic and diastolic blood pressure. In addition, felodipine significantly lowered the values of blood pressure reached during both dynamic exercise (bicycle ergometer, p less than 0.001) and isometric exercise (handgrip, p less than 0.001).

Effect of enalapril on parasympathetic activity.

To evaluate the effect of converting enzyme inhibition induced by enalapril on parasympathetic activity, we studied ten essential hypertensive patients, age range 38-58 years, WHO I-II. Parasympathetic evaluation was obtained by measuring the variation of heart period (VHP) during at least 1 minute of steady-state, regular respiration. VHP was derived from the difference between the mean of all maximum and the mean of all minimum heart periods. The higher the VHP, the higher the parasympathetic control of heart rate and vice versa. VHP was measured supine and with tilting (30 degrees, 60 degrees, 85 degrees). Blood pressure was reduced after 1 month of enalapril treatment, while the heart rate did not change. VHP increased at the end of enalapril treatment compared with placebo: in the supine position it increased from 36 +/- 3.2 ms to 44 +/- 3.5 ms, p less than 0.01. VHP was also increased by enalapril at 30 degrees (p less than 0.05) and 60 degrees (p less than 0.05), while no difference was observed at 85 degrees between placebo and enalapril. A positive correlation was found between supine enalapril changes of VHP and those of systolic and diastolic BP. In conclusion, enalapril seems to increase parasympathetic cardiovascular control in essential hypertensive patients. This result might explain the lack of increase in heart rate that would be expected as a result of the vasodilating effect of enalapril.

Angiotensin converting enzyme inhibition, parasympathetic activity and exercise in essential hypertension.

Reduced parasympathetic activity has been reported in essential hypertension. Converting enzyme inhibition seems to increase parasympathetic tone. In order to evaluate the effects of enalapril on parasympathetic control of heart rate, the authors studied ten mild-to-moderate essential hypertensive patients (7 F, 3 M), treated for 2 weeks with placebo and for 1 month with enalapril. Compared to placebo, enalapril significantly reduced blood pressure (p less than 0.005 at least, both systolic and diastolic), without any change in heart rate. Enalapril enhanced parasympathetic activity as judged by the increased variation of heart period (VHP) during regular breathing. VHP was derived during continuous ECG recording by the difference between the mean of all maximum and minimum R-R intervals, taken as a measure of respiratory sinus arrhythmia: the higher the VHP, the higher the parasympathetic cardiac influence and vice versa. The response to exercise, used as an index of sympathetic stimulation, was not modified by enalapril: the heart rate peak reached during either static (hand grip) or dynamic (bicycle ergometer) exercise and the slope of the increase in blood pressure were unchanged. Therefore, enalapril appears to increase parasympathetic tone in essential hypertension, without any interference with sympathetic adaptation to stress.

Effect of enalapril at rest and during isometric and dynamic exercise in essential hypertensive patients.

Vasodilator drugs reduce peripheral vascular resistance but lead to a secondary baroreflex-mediated chronotropic effect. After angiotensin-converting enzyme inhibition, blood pressure falls without associated tachycardia. In a previous study it was observed that enalapril increased vagal tone in essential hypertensive patients. In order to evaluate the effect of enalapril on sympathetic stimulation 10 mild to moderate hypertensive patients were studied during static (hand grip) and dynamic exercise (bicycle ergometer), after 2 weeks of placebo and after 1 month of treatment with 20-40 mg enalapril once daily. Enalapril significantly reduced blood pressure and the rate-pressure product at rest and at peak dynamic exercise. There was no effect on supine and maximal heart rate. Enalapril also significantly reduced blood pressure during hand grip, but did not interfere with the rate of the increase. Thus, enalapril does not seem to interfere with sympathetic adaptation to stress.

Calcium entry blockade, autonomic activity and exercise performance in essential hypertensive patients.

Vasodilator drugs lead to secondary baroreflex mediated chronotropic effects. The aim of the present study was to evaluate long term therapy with nicardipine, a calcium antagonist, on exercise performance and autonomic nervous system activity. Nicardipine was administered to 10 untreated mild-moderate essential hypertensive patients. Isometric (hand grip) and dynamic (bicycle ergometer) exercise, and parasympathetic activity evaluated on the basis of Variation of Heart Period (VHP) during regular breathing were determined. Blood pressure was significantly lowered by nicardipine both supine and standing (p less than 0.001). Heart rate did not change. The increase of blood pressure during isometric and dynamic exercise was similar both before and during nicardipine. The increase of heart rate during dynamic exercise was lowered by nicardipine. The lack of basal supine and standing chronotropic activation and the smaller increase of heart rate during bicycle ergometer could be explained by the observed increase in parasympathetic activity, as indicated by the rise of VHP.