Early and late results of intracoronary arterial stenting after coronary angioplasty in dogs

Intimal dissection with acute closure represents the major complication associated with percutaneous transluminal coronary angioplasty (PTCA). Intracoronary stent devices offer the possibility of treatment for this sequela. We developed a balloon catheter-mounted, flexible coil stent for use in such cases. To determine the utility of this device and its immediate and long-term influence on arterial patency, 39 mongrel dogs had the stent placed after PTCA of the left circumflex or left anterior descending coronary arteries. Thirteen animals were treated before and after the procedure with warfarin. In this group there were three early deaths associated with stent thrombosis. Twenty-six animals were subsequently treated before and after with aspirin and dipyridamole. There were no early thrombotic events associated with stent placement in these animals. Late arteriographic examination revealed patent vessels in all dogs. Diameter stenosis for warfarin-treated dogs was 8 +/- 5% (mean +/- SD) at 2 months (n = 9), 6 +/- 4% at 6 months (n = 5), and 11 +/- 7% at 12 months (n = 3). Diameter stenosis for aspirin/dipyridamole-treated dogs was 9 +/- 3% at 2 months (n = 8), 8 +/- 5% at 6 months (n = 12), and 5% at 12 months (n = 1). Light and scanning electron microscopic analyses of stented arteries demonstrated incorporation of the stent wires into the arterial wall. Early findings included mild thrombosis localized to areas of wire entrenchment followed by rapid regrowth of endothelial and/or pseudoendothelial cells over trenches, exposed wires, and elastica.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of Patients with High-Risk Stage II Colon Cancer for Adjuvant Therapy

Purpose Adjuvant therapy for Stage II colon cancer remains controversial but may be considered for patients with high-risk features. The purpose of this study was to assess the prognostic significance of commonly reported clinicopathologic features of Stage II colon cancer to identify high-risk patients. Methods We analyzed a prospectively maintained database of patients with colon cancer who underwent surgical treatment from 1990 to 2001 at a single specialty center. We identified 448 patients with Stage II colon cancer who had been treated by curative resection alone, without postoperative chemotherapy. Results With median follow-up of 53 months, 5-year disease-specific survival for this cohort was 91 percent. Univariate and multivariate analyses identified three independent features that significantly affected disease-specific survival: tumor Stage T4 (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1–6.2; P = 0.02), preoperative carcinoembryonic antigen >5 ng/ml (HR, 2.1; 95 percent CI, 1.1–4.1; P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95 percent CI, 1–4.4; P = 0.04). Five-year disease-specific survival for patients without any of the above poor prognostic features was 95 percent; five-year disease-specific survival for patients with one of these poor prognostic features was 85 percent; and five-year disease-specific survival for patients with ≥2 poor prognostic features was 57 percent. Conclusions Patients with Stage II colon cancer generally have an excellent prognosis. However, the presence of multiple adverse prognostic factors identifies a high-risk subgroup. Use of commonly reported clinicopathologic features accurately stratifies Stage II colon cancer by disease-specific survival. Those identified as high-risk patients can be considered for adjuvant chemotherapy and/or enrollment in investigational trials. Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 6, 2007. Reprints are not avaliable.     

Hyperkalemia in the Hypertensive Patient

Purpose of Review

Hyperkalemia develops in a patient with systemic arterial hypertension (HTN) if one or more risk factors are present, namely chronic kidney disease (CKD) (especially severe stage 4-5 CKD), diabetes mellitus (DM), heart failure (HF), or pharmacological therapies that interfere with potassium homeostasis, mainly through renin-angiotensin-aldosterone inhibition (RAASi). Hyperkalemia is a considerable reason of morbidity (emergency department (ED) visits and hospitalizations) and portends a higher mortality risk in patients at risk; for instance, hyperkalemia increases the risk of mortality within 1 day of a hyperkalemic event. This review aims to identify the risk factors for high-serum potassium, highlight the risk versus benefit of RAASi in certain patient populations, and outline preventive as well as therapeutic strategies for hyperkalemia.

Recent Findings

A growing body of evidence supports the safety and efficacy of cation-exchange resins, patiromer, or sodium zirconium cyclosilicate, in patients with a compelling indication for RAASi, yet in whom such therapy was complicated by hyperkalemia, allowing these patients to benefit from continued RAASi therapy.

Summary

In summary, novel cation exchange polymers present the clinician with a new and safe strategy to address hyperkalemia in patients with a compelling indication for ongoing RAASi therapy instead of withdrawal of such therapy.

     

Advances in neuroimaging for HIV-1 associated neurological dysfunction: clues to the diagnosis, pathogenesis and therapeutic monitoring

Persons with advanced human immunodeficiency virus type one (HIV-1) infection seek medical advice for a wide range of neurological disorders including, but not limited to, peripheral neuropathy, toxoplasmosis, cryptococcal meningitis, cytomegalovirus retinitis progressive multifocal leukoencephalopathy, lymphoma and dementia. The diagnosis of HIV-1-associated dementia (HAD) induced as a direct consequence of HIV infection of the brain comes commonly by exclusion. Diagnostic decisions can often be clouded by concomitant depression, motor impairments, and lethargy that follow debilitating immune suppression and weight loss. Indeed, cognitive, motor and behavior abnormalities underlie a variety of neurological dysfunctions associated with advanced HIV-1 infection. Thus, even combinations of clinical, laboratory and neuroimaging tests [for example, magnetic resonance imaging (MRI), computed tomography (CT), single photon emission computed tomography (SPECT) and positron emission tomography (PET)] often fail to provide conclusive diagnostic information. Nonetheless, the recent development of quantitative MR spectroscopic imaging has improved diagnostic possibilities for HAD. We are pleased to discuss these developments as well as taking a forward look into what will soon be made available to improve neuroimaging diagnostic precision. New MR and SPECT testing are being developed in our laboratories and elsewhere both for animal model systems and in humans with HIV-1 disease. Such tests can facilitate dynamic measures of HIV-1 neuropathogenesis providing information for disease events that even 2 years ago were unattainable.     

Parallel adrenal and renal abnormalities in young patients with essential hypertension

To determine whether the previously described abnormalities in adrenal secretion and renal blood flow in essential hypertension are associated, we examined the responses to the relevant systems in 18 patients with essential hypertension. Young patients, under 30 years of age, were studied to minimize the likelihood that the phenomena were secondary to long-standing hypertension. To achieve a wide span of sodium balance, studies were performed during a high (200 mEq) sodium intake, a restricted (10 mEq) sodium intake and a restricted sodium intake supplemented by a further short-term diuretic-induced volume deficit (furosemide, 180 to 300 mg, to reduce body weight by 1 to 1.5 kg). The indexes measured included cardiac output (indocyanine green indicator dilution), plasma volume (¹²⁵I albumin space), renal blood flow (radioxenon transit), plasma renin activity and aldosterone levels and aldosterone secretory rate. All of these variables, with the exception of Mood pressure and total peripheral resistance, were within the normal range during the two diets. However, the aldosterone secretory response to diureticinduced volume depletion on a low-sodium diet was clearly blunted in nine subjects. These nine subjects (abnormal responders) had a virtually absent aldosterone increment (23 ± 34 μg per 24 hours) compared with the normal responders (502 ± 70 μg per 24 hours). In addition, renal blood flow was significantly higher in these same nine subjects during both a high sodium intake (434 ± 19 versus 342 ± 26 ml/100 g per minute) and a restricted sodium intake (446 ± 11 versus 285 ± 39 ml/100 g per minute). Yet, there were no significant differences between these two groups in sodium or potassium balance, blood pressure, plasma volume, cardiac index or plasma renin activity during a high or low sodium intake. Normally, control of both aldosterone release by the adrenal and renal perfusion is dominated by angiotensin; an apparently blunted response of both systems suggests that there may be a generalized abnormality in the way angiotensin interacts with its target tissues in many young patients with essential hypertension.     

Galantamine maintains ability to perform activities of daily living in patients with Alzheimer's disease

OBJECTIVES: To examine the effect of galantamine on activities of daily living (ADLs) with respect to baseline dementia severity, correlation with cognitive and global function, specific ADLs affected, and maintenance of ADL independence. DESIGN: Secondary analysis of a 5-month randomized, placebo-controlled trial. SETTING: Multiple U.S. clinical centers. PARTICIPANTS: Six hundred fifty-nine patients with mild to moderate Alzheimer's disease (AD) who completed 5 months of treatment. INTERVENTION: Galantamine at a maintenance dose of 16 or 24 mg/d. MEASUREMENTS: The AD Cooperative Study ADL Inventory (ADCS/ADL). RESULTS: Galantamine resulted in more improvement in ADCS/ADL scores than placebo regardless of baseline dementia severity, with the greatest differences occurring in patients with more severe disease. Changes in ADCS/ADL scores correlated significantly with change scores on the cognitive subscale of the AD Assessment Scale (r=-0.24). Galantamine treatment resulted in maintenance or improvement of basic and instrumental ADLs, and change from baseline to Month 5 in scores for each individual ADL item favored galantamine over placebo in three of six basic ADLs and six of 17 instrumental ADLs. CONCLUSION: Galantamine has a favorable effect on ADL performance in patients with AD, detectable after 5 months of treatment, regardless of dementia severity. The ADCS/ADL appears to better measure distinct abilities that may be relevant not only in clinical trials but also in individual patients than do cognitive assessments.     

HIV prevalence and risk behaviours for HIV transmission in South Australian prisons

During the latter half of 1989, HIV prevalence in South Australian prisoners was 1.4%. The prevalence of HIV infection across the prison system did not change significantly during 1989 but there was clustering of HIV-infected prisoners in some prisons. Almost half the prisoners from all of the South Australian prisons agreed to participate in our studies, from which we estimate that about 42% of prisoners engage in risk behaviours at least once while incarcerated. Prisoners estimated that 36% of all prisoners inject drugs intravenously at some stage during their stay and that 12% engage in anal intercourse at least once. Interviews with former prisoners who had a history of intravenous drug use revealed that about half had injected themselves while in prison, 60% shared needles and most did not clean shared needles adequately. Most of these prisoners injected themselves once a month or less frequently. The conditions for spread of HIV within the prison system exist but at the current prevalence of infection, transmission can be expected to be infrequent. The opportunity exists now to improve and expand preventive measures.     

Hypertrophy, fibrosis and diastolic dysfunction in early canine experimental hypertension.

To examine the relations among hypertrophy, fibrosis and diastolic performance in early experimental hypertension, 18 control dogs and 12 dogs with experimental left ventricular hypertrophy were studied. Diastolic function was impaired in dogs with left ventricular hypertrophy, with decreased Doppler early to atrial inflow velocity ratio (E/A) (1.35 versus 1.72), increased atrial filling fraction (35% versus 29%), decreased sonomicrometric peak rates of wall thinning (-2.01 versus -3.37 liters/s) and filling (4.33 versus 6.64 liters/s) and prolonged time constant of isovolumetric relaxation (tau; 34.3 versus 28.1 ms). Neither chamber stiffness (k; P = AekV) nor passive elastic stiffness (E; E = k sigma, where sigma = stress) was increased. At postmortem examination, the hypertensive left ventricle weighed significantly more than normal (116 versus 80 g; p less than 0.01) and had greater muscle fiber diameter at endocardial and epicardial sampling sites in the apical free wall, basal free wall and septum (mean diameter 50 +/- 8 microns in hypertensive dogs, 37 +/- 8 microns in normal dogs; p less than 0.01). In contrast, neither percent fibrosis (1.2 +/- 0.8 versus 0.9 +/- 0.6 in normal dogs) nor fibrotic volume (1.21 +/- 0.63 versus 0.72 +/- 0.42%/g in normal dogs) was significantly increased. Peak volumetric filling rate was inversely related to fiber diameter (r = -0.74, p less than 0.001), although no variable of left ventricular function was significantly related to percent or volume fibrosis (all r less than 0.60, all p greater than 0.05). Thus, diastolic dysfunction may exist in the setting of hypertrophy without significant fibrosis. Increased myocyte size was associated with early diastolic filling abnormalities characteristic of the hypertensive left ventricle. Fibrosis appears to be a less important determinant of diastolic performance.     

Monorail™ Piccolino catheter: A new rapid exchagne/ultralow profile coronary angioplasty system

The Monorail^TM Piccolino coronary angioplasty balloon catheter (MBC) was evaluated on 118 patients at two centers. Technical success was achieved in 110 patients (93%). Time for catheter exchange and total fluoroscopy time were significantly lower for the Monorail catheter than with standard equipment (exchange time 97 vs. 170 seconds P <.05 and fluoroscopy time 17 vs. 88 seconds P < 0.001). The advantages of rapid exchange and the ability of utilize 2 Monorail balloon catheters through one 9F guiding catheter for simultaneous inflations allowed for maximal flexibility in treating patients with bifurcation lesions. The double wire approach utilizing one Monorail balloon catheter with a 7F guiding catheter was also technically successful. The Monorail^TM Piccolino balloon catheter has unique features that allow for greater ease of operator use, rapid catheter exchange, and optimal angiographic visualization. It is felt that this catheter design provides distinct advantages over standard angioplasty equipment.