Salivary Fructosamine as a Noninvasive Glycemic Biomarker: A Systematic Review.

BACKGROUND: Standard diagnostic and monitoring methods for glycemic status involve invasive sample collection through venous puncture or fingerstick. Recent attention has been focused on exploring noninvasive methods through oral biofluids. Specifically, serum fructosamine has been established as a short-term (2- to 3-wk) marker of disease status in patients with diabetes. Fructosamine measured through noninvasive means such as saliva has shown promise, but its clinical applicability is unknown. OBJECTIVE: Evaluate the available evidence on using salivary fructosamine as a reliable noninvasive marker to screen and diagnose patients with diabetes mellitus in the clinical setting. A comparative analysis of the correlative accuracy of salivary fructosamine measurements with established blood glycemic biomarkers such as serum fructosamine, blood glucose, and HbA1c will be conducted. METHODS: Six electronic databases (PubMed, PubMed Central, MEDLINE, EMBASE, Scopus, Cochrane Library) were searched for original research papers (clinical and animal studies) that were relevant to the objective of this systematic review. The search was initiated on May 28, 2020. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Bias risk assessment, overall quality, and level of evidence were based on the Oxford Centre for Evidence-Based Medicine, Appraisal Tool for Cross-Sectional Studies, and Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies tool. Heterogeneity was assessed using the National Institutes of Health quality assessment tool for cross-sectional studies. RESULTS: A total of 174 records were identified. Full-text articles screened for eligibility (n = 21) identified only 6 original research articles relevant to the research question and were thus included in the systematic review. The types of studies identified were cross-sectional and in vivo studies. Three studies (3/6) showed positive correlation of salivary fructosamine with blood glucose levels, while 1 study (1/6) demonstrated a positive correlation with glycated hemoglobin (HbA1c). Limitations related to sample size and selection were identified along with a fair level of interstudy heterogeneity. CONCLUSION: Based on the evidence evaluated, the utility of salivary fructosamine as a noninvasive marker to screen and diagnose patients with diabetes is doubtful. The overall level of evidence was low (IIIB) and the risk of bias was determined to be high. KNOWLEDGE TRANSFER STATEMENT: Further evidence in the form of large-scale well-controlled studies is needed prior to recommending salivary fructosamine as a noninvasive diagnostic tool for glycemic status in patients with diabetes mellitus.

Long-term (three-year) prognosis of patients treated with reperfusion or conservatively after acute myocardial infarction. Israeli Thrombolytic Survey Group.

OBJECTIVES: This survey sought to assess the frequency of the use of thrombolytic therapy, invasive coronary procedures (ICP) (angiography, percutaneous transluminal coronary angioplasty and coronary artery bypass grafting [CABG]), variables associated with their use, and their impact on early (30-day) and long-term (3-year) mortality after acute myocardial infarction (AMI). BACKGROUND: Few data are available regarding the implementation in daily practice of the results of clinical trials of treatments for AMI and their impact on early and long-term prognosis in unselected patients after AMI. METHODS: A prospective community-based national survey was conducted during January-February 1994 in all 25 coronary care units operating in Israel. RESULTS: Among 999 consecutive patients with an AMI (72% men; mean age 63+/-12 years) acute reperfusion therapy (ART) was used in 455 patients (46%; thrombolysis in 435 patients [44%] and primary angioplasty in 20 [2%]). Its use was independently associated with anterior AMI location and hospitals with on-site angioplasty facilities, whereas advancing age, prior myocardial infarction (MI) and prior angioplasty or CABG were independently associated with its lower use. The three-year mortality of patients treated with ART was lower than in counterpart patients (22.0% vs. 31.4%, p = 0.0008), mainly as the result of 30-day to 3-year outcome (12.4% vs. 21.1%; hazard ratio = 0.73, 95% confidence interval [CI] 0.52 to 1.03). Independent predictors of long-term mortality were: age, heart failure on admission or during the hospitalization, ventricular tachycardia or fibrillation and diabetes. The outcome of patients not treated with ART differed according to the reason for the exclusion, where patients with contraindications experienced the highest three-year (50%) mortality rate. After ART, coronary angiography, angioplasty and CABG were performed in-hospital in 28%, 12% and 5% of patients, respectively. Their use was independently associated with recurrent infarction or ischemia, on-site catheterization or CABG facilities, non-Q-wave AMI and anterior infarct location. In the entire study population, and in patients with a non-Q-wave AMI, performance of ICP was associated with lower 30-day mortality (odds ratio [OR] = 0.53, 95% CI 0.25 to 0.98, and OR = 0.21, 0.03 to 0.84, respectively), but not thereafter. CONCLUSIONS: This survey demonstrates the extent of implementation in daily practice of ART and ICP and their impact on early and long-term prognosis in an unselected population after AMI.

Correlation of exercise-induced ST depression in precordial electrocardiographic leads after inferior wall acute myocardial infarction with thallium-201 stress scintigraphy, coronary angiography and two-dimensional echocardiography.

Fifty-eight of 220 consecutive patients had exercise-induced ST depression in some or all precordial leads 3 to 12 months after a first inferior myocardial infarction. All 58 patients underwent thallium-201 exercise testing, 2-dimensional echocardiography and coronary angiography. ST depression was confined to leads V1-4 in 22 patients (group A); thallium-201 exercise testing showed reversible anterior perfusion defects and left anterior descending coronary artery disease in 11 of the 22 patients (50%). None of the other 11 with negative thallium-201 exercise test results had significant left anterior descending narrowing, and the anterior ST depression could be explained by asynergy of the posterior wall found on 2-dimensional echocardiography in 10. ST depression appeared in leads V5-6 in 22 patients (group B); reversible anterior perfusion defects and left anterior descending disease was demonstrated in 18 patients (82%). In the other 4 patients posterior wall asynergy was demonstrated. ST depression was seen from leads V1-6 in 14 patients (group C); reversible anterior perfusion defects were seen in 6 patients (43%), 5 of whom had significant left anterior descending disease. Among the other 8 patients without reversible anterior perfusion defects, posterior wall asynergy was found in 6.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency and distribution of atherosclerotic plaques in the thoracic aorta as determined by transesophageal echocardiography in patients with coronary artery disease.

The frequency, distribution, and severity of thoracic aortic plaques were evaluated by transesophageal echocardiography in 152 consecutive patients undergoing coronary arteriography. Coronary artery disease (CAD) was defined as > or = 50% stenosis of > or = 1 major branch. Atherosclerotic plaques were detected in the aorta in 90 of the 97 patients (93%) with CAD, but in only 12 of the 55 patients (22%) with normal coronary arteries. Atherosclerotic plaques in patients with CAD were found predominantly in the descending aorta (in 93%) and in the aortic arch (in 80%), whereas the ascending aorta was the least involved (in 37%). In the descending aorta, 58% of the plaques were complex (>3 mm thick, ulcerated, mobile, or calcified), and in the aortic arch, 40% of the plaques were so classified. Complex plaques were not found in the ascending aorta. The presence of an atherosclerotic plaque in the descending aorta had a sensitivity and a specificity for the prediction of CAD of 93% and 78%, respectively. In the ascending aorta, the sensitivity was lower (37%) but the specificity was higher (100%). The sensitivity of aortic plaques for the prediction of CAD was high in all age groups. Its specificity in subjects >63 years was lower than in younger subjects: 64% versus 90%, respectively. Multivariate logistic regression analysis showed that aortic plaques were a stronger predictor of CAD than were conventional risk factors.

Relation of coronary artery disease to atherosclerotic disease in the aorta, carotid, and femoral arteries evaluated by ultrasound.

This prospective study was conducted to correlate the presence of angiographically significant coronary artery disease (CAD) and atherosclerotic disease in the aorta, carotid, and femoral arteries as measured by ultrasound. One hundred two consecutive patients admitted for coronary angiography for suspected CAD participated in the study. All patients underwent transesophageal echocardiography for the evaluation of thoracic aortic atherosclerosis and B-mode ultrasound for evaluation of carotid and femoral atherosclerosis. Intimal-medial thickness > 1 mm in the thoracic aorta or peripheral vessels was considered as evidence of atherosclerosis. Patients with CAD (n = 64) had a significantly higher incidence of atherosclerotic plaques in the thoracic aorta, carotid, and femoral arteries than subjects with normal coronary arteries: 91%, 72%, 77% vs 31%, 47% and 42%, respectively. Extracoronary plaque was a stronger predictor of CAD than conventional risk factors. Evidence of plaque in patients younger than median age (64 years) had a higher specificity than in patients above median age (77% vs 40%, respectively, p <0.0001). Plaque score of the extracardiac vessels was significantly higher in patients with multivessel CAD than in patients with 1-vessel CAD disease and in subjects with normal coronary arteries (p <0.001). Thus, atherosclerotic plaques in the aortic and femoral arteries and, to a lesser extent, in the carotid arteries are strong predictors of CAD.

Findings of automatic border detection in subjects with left ventricular diastolic dysfunction by Doppler echocardiography.

Left ventricular automatic border detection (ABD) patterns were defined in the parasternal short-axis and the apical four-chamber views and were compared with pulsed-wave diastolic Doppler flow-velocity patterns of the mitral valve in 49 subjects (aged 39 to 87 years), 10 selected normal individuals, and 39 consecutive patients with high-quality echocardiographic Doppler studies and relaxation abnormalities (Doppler peak early diastolic velocity/peak late velocity ratio < 1). Both short-axis and apical four-chamber views were useful in the assessment of diastolic function by ABD. However, in subjects with high-quality two-dimensional echocardiographic Doppler studies, ABD was technically more feasible in the apical four-chamber view (97%; 38/39 subjects) than in the short-axis view (64%; 25/39 subjects) and correlated better with Doppler parameters. Compared with normal subjects, patients with abnormal Doppler relaxation patterns showed significant differences in diastolic filling indexes obtained by the ABD technique. The ratio of peak rapid filling rate/peak atrial filling rate (PRFR/PAFR) obtained from the dA/dt waveform in the apical four-chamber view had the highest correlation with Doppler indexes (r = 0.79). A PRFR/PAFR ratio of 1.5 best discriminated between normal individuals and subjects with relaxation abnormalities, with high sensitivity and specificity (95% and 100%, respectively). The PRFR/PAFR ratio obtained from the dA/dt waveform seemed to be a simple and useful method to distinguish between normal and abnormal left ventricular diastolic filling, as defined by Doppler echocardiography.

The effect of prophylactic nifedipine on renal function in patients administered contrast media.

STUDY OBJECTIVE: To determine if prophylaxis with nifedipine could decrease the frequency of contrast medium-induced renal impairment. DESIGN: Prospective, randomized clinical trial. SETTING: A university-affiliated hospital. PATIENTS: Patients undergoing scheduled radiologic examinations involving infusion of contrast media. INTERVENTIONS: Forty-two patients were randomized to receive nifedipine 10 mg orally 1 hour before the imaging procedure, and 43 to receive no treatment. MEASUREMENTS AND MAIN RESULTS: Baseline serum creatinine levels were compared with maximum levels 24 and 48 hours after administration of contrast medium. No statistically significant difference was seen in either the mean change or mean percentage change in serum creatinine between the control and nifedipine groups. The mean changes in serum creatinine were +7.4 mumol/L in the control group and +2.7 mumol/L in the nifedipine group (p = 0.33); the mean percentage changes were +10.2% and +4.8%, respectively (p = 0.54). CONCLUSION: Regardless of statistical analysis, it is unlikely that elevations in serum creatinine of this magnitude (< 0.1 mg/dl) are of clinical significance. We therefore conclude that prophylactic nifedipine is not clinically beneficial in preserving renal function in patients receiving contrast medium and that the agent should not be routinely administered for this purpose.

[Persistent neutrophilic meningitis in a patient with the acquired immunodeficiency syndrome]. / Meningite neutrofílica persistente em paciente com síndrome de imunodeficiência adquirida.

Persistent neutrophilic meningitis is rarely found and it is characterized by predominance of the number of neutrophils in samples of C SF (cerebrospinal fluid) from the patient after seven days of treatment. The above patient in HIV positive; he has developed fever and mental disorder for 4 months and has presented neutrophilic pleocytosis in analysis of CSF for more than 5 months. Since the beginning or the treatment he has taken antituberculous drugs and corticosteroids. For 3 months, the serologic evaluation, smears and cultures were negative. On the 60th day in hospital, the investigation of acid-fast bacilli in CSF was positive and culture confirmed the presence of Mycobacterium tuberculosis resistant to isoniazid. Several factors that may have caused this uncommon development were discussed: the disturbance of cell-mediated immunity, mainly in release of IL 8 and TNF, the simultaneous use of medicines that could alter the CSF concentration of antituberculous drugs, and the increasing number of multiresistant strains.

Familial medullary sponge kidney in association with congenital absence of teeth (anodontia).

Medullary sponge kidney was found in association with congenital absence of teeth (anodontia) in 3 siblings of a single family. Anodontia occurs in the rare familial syndrome of ectodermal dysplasia, but its association with a renal (mesodermal) anomaly is not known. The present report lends further support to a possible hereditary etiology for medullary sponge kidney.

Neurocutaneous island flaps in the hand: anatomical basis and preliminary results.

The neurocutaneous flap is an axial flap composed of one vein and one nerve, the arterial vascularisation of which is provided by the vascular plexus around and inside the nerve. The vascularisation of the radial and ulnar nerves on the dorsal aspect of the hand were studied in 20 fresh upper limbs. There is always a consistent arterial longitudinal plexus alongside the nerves, which links the cutaneous perforating arteries. On the basis of our anatomical findings, neurocutaneous island flaps with retrograde flow were raised on the hands of five patients and are reported on.

Aborted sudden death in a young patient with isolated granulomatous myocarditis.

A young athlete was successfully resuscitated from ventricular fibrillation. Subsequently severe heart failure developed and endomyocardial biopsy showed granulomatous myocarditis. Following steroid therapy, repeated biopsies demonstrated partial resolution of the inflammatory changes and mild myocardial fibrosis; the granulomas disappeared, and the patient recovered both clinically and haemodynamically. Three years later, the patient is asymptomatic, is practising long distance jogging, has a normal left ventricular ejection fraction and no evidence of arrhythmias.

Residual left ventricular function and prognosis of patients with asymmetric septal hypertrophy recovering from acute myocardial infarction.

The prognosis of patients recovering from acute myocardial infarction (MI) depends mainly on their residual left ventricular (LV) function. In patients with asymmetric septal hypertrophy (ASH) who are recovering from MI, a larger functioning myocardial mass may remain. However, the frequency of ASH in these patients has not yet been described. Predischarge echocardiography, radionuclide ventriculography, and treadmill stress tests were performed in 403 consecutive patients who had recovered from acute MI. Eighty-eight patients (22%) had ASH with septal thickness greater than or equal to 1.3, and 32 (8%) had septal thickness greater than or equal to 1.5 cm. One hundred thirty-six patients who had recovered from a first MI and had no ASH served as control subjects. Left ventricular ejection fraction (LVEF) in the group with ASH was significantly higher than in control subjects (61% vs 50%; p = 0.0001). LV end-diastolic diameter (LVD(d] and E point septal separation (EPSS) were smaller in the group with ASH (4.9 cm and 5.4 mm) than in the control group (5.5 cm and 10.5 mm). The frequency of positive treadmill test results, angina pectoris, recurrent MI, heart failure, and death during a 22-month follow-up period was similar in both groups. Fifty subjects in the control group were matched with 50 patients from the group with ASH on the basis of maximal level of creatine phosphokinase, location of infarct, and presence or absence of hypertension, and the difference between the two groups was even more marked (LVEF 48% vs 61%, respectively; p = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of transdermal nicotine patches on ambulatory ECG monitoring findings: a double-blind study in healthy smokers.

The cardiovascular effects and safety of transdermal nicotine patches were assessed in 50 healthy smokers using repeated 48 hour ambulatory electrocardiographic monitoring as a part of a smoking cessation program. Following baseline measurements, subjects were randomized to active (n = 25) or placebo (n = 25) treatment groups for a period of 2 weeks. Twenty-two patients in each group completed the trial. During the treatment period, subjects also received behavioral supportive therapy. Heart rate and blood pressure were significantly reduced relative to baseline both groups. In the active treatment group, mean values at baseline and after 2 weeks of double-blind treatments were as follows: heart rates, 74.0 and 71.3 beats/min, respectively; systolic blood pressure, 108.9 and 106.9 mmHg; and diastolic blood pressure, 69.7 and 68.2 mmHg, respectively. Values for the placebo group were as follows: heart rate, 73.2 and 69.6 beats/min; systolic blood pressure, 110.6 and 105.3 mmHg; diastolic blood pressure, 71.4 and 70.5 mmHg. The confidence intervals of the mean for the differences between the groups are as follows: heart rate, -4.0 +8.2; systolic blood pressure, -6.7, +10.1; diastolic blood pressure, -7.9, +3.9. There were no changes in the frequency of atrial or ventricular arrhythmia as documented by repeated 48 hour ambulatory ECG recordings from baseline period before stopping smoking compared with the treatment period in the active as well as in the placebo groups. No ischemic events were detected in any of the volunteers during either the baseline or treatment periods. As a measure of smoking abstinence, we assessed the level of carbon monoxide in expired air; in the active group, the mean levels fell from 14.2 to 4.4 ppm after smoking cessation and in the placebo group from 13.2 to 4.2 ppm. The mean urine cotinine level fell from 8.18 mmol/l at baseline to 5.74 mmol/l after 2 weeks of treatment in the active group and from 8.78 to 3.93 mmol/l in the placebo group. The number of cigarettes smoked per week in both treatment groups was significantly reduced: from 175.2 to 8.4 for the active group and from 136 to 8.6 for the placebo group. Eleven out of 22 subjects in each group quit smoking completely. Smoking withdrawal symptoms during the first week of treatment were more severe in the placebo group than in those on active treatment. There were no significant side effects in either the placebo or the active treatment groups. These results indicate that nicotine delivered by transdermal system is free of cardiac adverse effects in healthy volunteers.

Cardiovascular safety of transdermal nicotine patches in patients with coronary artery disease who try to quit smoking.

Nicotine patches are commonly used by people who try to quit smoking. Because high doses of nicotine may increase heart rate and potentiate cardiac arrhythmia or ischemia, its use in patients with coronary artery disease was investigated. The objective was to assess the cardiovascular safety of nicotine patches in patients with coronary artery disease (CAD) who try to quit smoking. The study was conducted in a double-blind, placebo-controlled, randomized fashion over a 2-week period. One hundred and six patients with CAD who wished to stop smoking and were taking part in a smoking cessation program were included. Fifty-two patients received nicotine patches (Nicotinell) and 54 received placebo patches. The cardiovascular effects of nicotine patches were assessed by repeated ambulatory ECG monitoring (AEM) and exercise testing. There were no changes in the resting heart rate and in the systolic or diastolic blood pressure between the screening and the two phases of the study in both the Nicotinell and placebo groups. Repeated 48-hour AEM revealed that there were no significant changes in the number and duration of ischemic episodes in both groups. There was no change in the frequency of atrial or ventricular arrhythmias. Exercise duration and time to 1-mm ST-segment depression increased in both groups during the double-blind treatment phase. More patients in the Nicotinell group claimed tobacco abstinence compared with the placebo group (27% vs. 13%). The use of nicotine patches did not cause aggravation of myocardial ischemia or arrhythmia in coronary patients and therefore can be used as a method to promote smoking cessation in this high-risk group.

Mortality trends in men and women with acute myocardial infarction in coronary care units in Israel. A comparison between 1981-1983 and 1992-1994. For the SPRINT and the Israeli Thrombolytic Survey Groups.

AIMS: To assess trends in the management and subsequent outcome in men and women in two cohorts of consecutive patients with acute myocardial infarction hospitalized in coronary care units in Israel, in the pre-reperfusion and the reperfusion eras. METHODS AND RESULTS: We compared trends in the in-hospital management, and 30-day and 1-year mortality in men and women in two cohorts of patients hospitalized with acute myocardial infarction in coronary care units in Israel, in the pre-reperfusion and the reperfusion eras. The first cohort of 5839 consecutive patients (4315 men, 74%) was from the Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) registry of 1981-1983; the second cohort of 1940 patients (1429 males, 74%) derived from two prospective nationwide surveys conducted in all coronary care units in Israel in January/February 1992 and 1994. The demographic and clinical characteristics of patients with acute myocardial infarction in both periods were comparable. Patients in 1992-94 received aspirin, angiotensin-converting enzyme inhibitors, beta-blockers and nitrates more frequently than in 1981-83. Thrombolysis, coronary angiography, angioplasty and bypass grafting were not used in 1981-83, whereas in 1992-94 these procedures were used in 45%, 28%, 11% and 4% of men, respectively, and in 39%, 20%, 9% and 3% of women, respectively. The 30-day age-adjusted mortality declined, in men, from 17.0% in 1981-83 to 10.8% in 1992-94 (multivariate-adjusted odds ratio [OR]=0. 69; 95% confidence interval [CI] 0.55 to 0.87), and the cumulative 1-year age-adjusted mortality declined from 24.6% to 16.9% (adjusted hazard ratio [HR]=0.70%; 95% CI 0.60 to 0.81). In women, the decline in mortality rates were of similar magnitude, from 24.0% to 15.1% (OR=0.70; 95% CI 0.52 to 0.94), and from 33.6% to 21.0% (HR=0.67; 95% CI 0.55 to 0.81), respectively. In both sexes, the decline in mortality was more marked in patients reperfused by thrombolysis and/or mechanical revascularization, but was also evident in non-reperfused patients. CONCLUSIONS: Despite higher mortality in both periods in women compared to men, the prognosis of men and women with acute myocardial infarction improved considerably during the last decade, with a similar decline in 1-year mortality of approximately 30%. The implementation in daily practice of new therapeutic modalities proven to be effective in clinical trials after acute myocardial infarction, probably played a major role in this favourable outcome in both sexes.

Skeletal muscle pathology in 2 siblings infected with Toxoplasma gondii.

Skeletal muscle can be the site of inflammatory diseases that lead to muscle weakness, pain, and increased myogenic serum enzymes. Most of these inflammatory myopathies are idiopathic. In some cases inflammatory myopathies are due to infectious agents. We describe the pathological aspects of muscle biopsies of 2 Brazilian siblings who acquired toxoplasmosis at the same time and in similar conditions. One developed a tetraplegia that was confirmed to be due to inflammatory myositis due to toxoplasma. The other developed myocarditis, with heart failure, without skeletal muscle weakness. In both cases many toxoplasma organisms were observed in the muscle biopsies, but in case 1 only was there an inflammatory myopathy with myofiber necrosis; the inflammatory cells were predominantly macrophages with some CD4+ cells and rare CD20+ cells. In case 1, expression of CD54 was observed in many inflammatory cells as well in endothelial cells, but only in endothelial cells in case 2. After treatment with clindamycin and corticosteroids both cases had only partial improvement, case 1 with a residual muscle weakness and case 2 with residual cardiac insufficiency (requiring digoxin). These cases show that the presence of the parasite in myofibers is not enough to induce an inflammatory myositis with muscle cell necrosis. This suggests that immunological disturbances may contribute to the development of inflammatory myositis due to toxoplasma.