Theta and alpha oscillatory signatures of auditory sensory and cognitive loads during complex listening.

The neuronal signatures of sensory and cognitive load provide access to brain activities related to complex listening situations. Sensory and cognitive loads are typically reflected in measures like response time (RT) and event-related potentials (ERPs) components. It's, however, strenuous to distinguish the underlying brain processes solely from these measures. In this study, along with RT- and ERP-analysis, we performed time-frequency analysis and source localization of oscillatory activity in participants performing two different auditory tasks with varying degrees of complexity and related them to sensory and cognitive load. We studied neuronal oscillatory activity in both periods before the behavioral response (pre-response) and after it (post-response). Robust oscillatory activities were found in both periods and were differentially affected by sensory and cognitive load. Oscillatory activity under sensory load was characterized by decrease in pre-response (early) theta activity and increased alpha activity. Oscillatory activity under cognitive load was characterized by increased theta activity, mainly in post-response (late) time. Furthermore, source localization revealed specific brain regions responsible for processing these loads, such as temporal and frontal lobe, cingulate cortex and precuneus. The results provide evidence that in complex listening situations, the brain processes sensory and cognitive loads differently. These neural processes have specific oscillatory signatures and are long lasting, extending beyond the behavioral response.

A cortical biomarker of audibility and processing efficacy in children with single-sided deafness using a cochlear implant.

The goals of the current study were to evaluate audibility and cortical speech processing, and to provide insight into binaural processing in children with single-sided deafness (CHwSSD) using a cochlear implant (CI). The P1 potential to acoustically-presented speech stimuli (/m/, /g/, /t/) was recorded during monaural [Normal hearing (NH), CI], and bilateral (BIL, NH + CI) listening conditions within a clinical setting in 22 CHwSSD (mean age at CI/testing 4.7, 5.7 years). Robust P1 potentials were elicited in all children in the NH and BIL conditions. In the CI condition: (1) P1 prevalence was reduced yet was elicited in all but one child to at least one stimulus; (2) P1 latency was prolonged and amplitude was reduced, consequently leading to absence of binaural processing manifestations; (3) Correlation between P1 latency and age at CI/testing was weak and not significant; (4) P1 prevalence for /m/ was reduced and associated with CI manufacturer and duration of CI use. Results indicate that recording CAEPs to speech stimuli in clinical settings is feasible and valuable for the management of CHwSSD. While CAEPs provided evidence for effective audibility, a substantial mismatch in timing and synchrony of early-stage cortical processing between the CI and NH ear remains a barrier for the development of binaural interaction components.

Statin adherence and LDL cholesterol levels. Should we assess adherence prior to statin upgrade?

BACKGROUND: Adherence to statin therapy has been shown to be suboptimal. In statin-treated patients with residual elevated low density lipoprotein cholesterol (LDL-C) levels the physician must decide whether to switch to a more potent statin or try and achieve better adherence. We examined the association between adherence and LDL-C within low, moderate and high intensity statin groups in a "real world" setting. METHODS: We assessed annual adherence by the mean MPR (Medication Possession Ratio = number of purchased/prescribed daily doses) in unselected patient group. Statins were stratified (ACC/AHA Guideline) into low, moderate and high intensity groups. The impact of adherence on LDL levels was assessed by LOESS (locally weighted scatter plot smoothing). RESULTS: Out of 1183 patients 173 (14.6%) were treated with low, 923 (78.0%) with moderate and 87 (7.4%) with high intensity statins. Statin intensity was inversely associated with adherence (MPR 77±21, 73±22 and 69±21% for low, moderate and high intensity respectively, p=0.018). Non-adjusted LDL levels decreased with higher adherence: a 10% adherence increase resulted in LDL decrease of 3.5, 5.8 and 7.1mg/dL in low, moderate and high intensity groups. Analysis of the adherence effect on LDL levels adjusted for age, DM and ischemic heart disease showed that MPR above 80% was associated with an additional decrease in LDL levels only in the high intensity group. CONCLUSIONS: Increased adherence to statins beyond an MPR of 80% improves LDL levels only among patients given high intensity therapy. Switching from lower to higher intensity therapy may be more effective than further efforts to increase adherence.

Lack of association between breast artery calcification seen on mammography and coronary artery disease on angiography.

OBJECTIVES: Some studies have found correlations between the presence of breast artery calcium (BAC) observed on routine mammograms and risk factors for coronary artery disease (CAD). The aim of this study was to investigate whether such calcifications could predict the presence of coronary atherosclerosis. METHODS: A total of 319 female patients between 50 and 70 years of age, 187 with significant CAD and 132 with angiographically normal coronary arteries, were randomly selected from a computerised database of our central catheterisation laboratory. The patients' mammograms were evaluated independently for the presence of BAC in a blinded fashion by an experienced breast radiologist, and additional clinical data were extracted from clinical charts. RESULTS: The women in the CAD group were older (62.5 vs 60.7 years, p=0.05) and had a higher prevalence of hypertension, diabetes mellitus and dyslipidaemia. Although the prevalence of BAC was marginally higher in the CAD group (43.9% vs 37.1%, p=0.138), this tendency was eliminated after controlling for confounders. Multiple regression analyses indicated that only age above 63 years (odds ratio [OR]=3.0, 95% confidence interval [CI]=1.8-4.9) and hypertension (OR=2.2, 95% CI=1.2-4.1), but not angiographic evidence of CAD (OR=1.0, 95% CI=0.6-1.6), predict with BAC on mammography. CONCLUSIONS: Despite correlation with some risk factors for CAD, the presence of BAC does not differentiate between patients with angiographic evidence of CAD and those with angiographically normal coronary arteries.

Dietary treatment of hypercholesterolemia: do dietitians do it better? A randomized, controlled trial.

PURPOSE: Current guidelines of the National Cholesterol Education Program (NCEP) recommend initial dietary counseling by physicians for most patients with hypercholesterolemia; referral to a registered dietitian and lipid-lowering drugs are recommended only for patients who remain hypercholesterolemic. We evaluated the incremental value of detailed nutritional counseling by dietitians when added to general nutritional advice provided by physicians. SUBJECTS AND METHODS: Hypercholesterolemic patients detected during a cholesterol screening project were randomly assigned to receive dietary counseling by a physician only (70 patients) or by a physician and a registered dietitian (66 patients). Patients were observed for 1 year to determine compliance with NCEP guidelines. RESULTS: At 3 months, the mean (+/- SD) decrease in the serum low-density lipoprotein (LDL) cholesterol level was 7% +/- 11% in the physician group and 12% +/- 10% in the dietitian group (P <0.004). A decrease of 10% or more in the LDL cholesterol level was seen in 25 patients (36%) in the physician group and 43 patients (65%) in the dietitian group (P <0.001). Only 40 (29%) of the patients in both groups achieved their NCEP target goals at 3 months. The majority of these were low-risk patients with an LDL cholesterol target goal of 160 mg/dL. At 12 months, both groups lost about half of the beneficial effects on LDL cholesterol levels, and the difference between the two groups diminished. CONCLUSIONS: The short-term reduction in LDL cholesterol level achieved after counseling by dietitians is superior to that achieved by physicians. However, long-term compliance remains inadequate. For patients at high risk, consideration should be given to a more aggressive dietary approach and possibly earlier introduction of lipid-lowering medications.

Age-related changes in the visual perception of phonologically significant contrasts.

The purpose of the present study was to determine whether the ability to speechread phonological contrasts is influenced by age. Forty-eight subjects were equally represented in three age groups: 8-9 years, 11-12 years and adults (20-29 years). The Hebrew version of the Speech Pattern Contrast (HeSPAC) test was administered by speechreading alone. Results showed that: age influenced performance; performance was contrast-dependent (place contrasts highly visible, manner and vowel height partially visible and voicing contrast invisible); hierarchy of contrast performance was similar for all age groups; Hebrew and English differ in the visual accessibility to speech contrasts in final voicing only; and females were found to be poorer speechreaders than males for the partially visible contrasts. The results suggest that speechreading at the phonological level follows a developmental course. The implications of these findings extend to recommendations provided to children in noisy listening conditions, speechreading training in hearing-impaired children and those with central auditory processing disorders (CAPD), and to the design of sensory aids.

Estrogen-progestin therapy and coronary heart disease in radiation-induced rectal telangiectases.

We describe two elderly men with preexisting coronary heart disease (CHD) and prostatic carcinoma who presented with intractable anemia due to radiation-induced rectal telangiectases and bleeding. Remission of the bleeding was achieved in both patients by treatment with an estrogen-progestin preparation. However, aggravation of the CHD occurred in both patients. We believe that estrogen-progestin preparations have a potential in the treatment of men with radiation-induced rectal telangiectases, but additional studies are needed to evaluate their long-term effects and optimal dose.

Lipolysis-induced partitioning of free fatty acids to lipoproteins: effect on the biological properties of free fatty acids.

Free fatty acids (FFA) released during the lipolysis of triglyceride (TG)-rich lipoproteins in vivo are generally believed to be bound to serum albumin. When hypertriglyceridemic (HTG) sera were lipolyzed in vitro by purified bovine milk lipoprotein lipase (LpL), there was an 11- to 18-fold increase in serum FFA levels, and a major portion (> 80%) of the FFA in serum was partitioned to lipoprotein fractions. The greatest portion (33%) of FFA in lipolyzed HTG serum was associated with newly formed flocculent remnants that banded just below low density lipoproteins (LDL) in the density gradient tube. Very low density lipoprotein (VLDL), LDL, and high density lipoprotein (HDL) fractions in lipolyzed HTG serum contained 18- to 29-times more FFA molecules than those in prelipolysis serum. Analysis of the fatty acyl chain composition of FFA in lipolyzed HTG serum showed that the extent of partitioning of saturated FFA into the lipoprotein fractions relative to that of polyunsaturated FFA was about 4.5- to 11-times greater than that partitioned into the free protein fraction; most (84%) of FFA partitioned into flocculent remnants were saturated fatty acids. In vivo lipolysis of TG-rich lipoproteins in HTG subjects, induced by heparinization, resulted in only a small (2.8-fold) increase in serum FFA and little or no increase in the partitioning of FFA to lipoproteins. However, in vitro incubation of the postheparin serum at 37 degrees C for 90 min resulted in a 2.9- to 6.8-fold increase in the serum FFA level and the partitioning of > 66% of total serum FFA into lipoprotein fractions. Studies of the interaction of various plasma fractions from control and in vitro lipolyzed HTG serum with cultured mouse peritoneal macrophages (MPM) showed that FFA partitioned to lipoprotein fractions were highly cytotoxic to cultured MPM, whereas FFA partitioned to albumin at a 10 x greater concentration were not cytotoxic. The cytotoxic potencies of FFA bound to lipoproteins and albumin were further compared after in vitro incorporation of FFA (oleic acids) into LDL and to albumin. FFA bound to LDL but not to albumin were cytotoxic to cultured MPM; the cytotoxicity of FFA bound to LDL was more closely related to the FFA to LDL-cholesterol molar ratio than to the total FFA concentration in the culture dish. The ability of FFA bound to LDL and albumin to induce foam cell formation was studied in THP-1 monocyte-derived macrophages, which were less susceptible to cytotoxicity produced by FFA bound to LDL than MPM.(ABSTRACT TRUNCATED AT 400 WORDS)

Methodological issues in conducting a community-based clinical drug trial.

OBJECTIVE: This paper explores the advantages and disadvantages of implementing a clinical drug trial in a closed community. METHODS: In the study we conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of an antacid containing aluminum hydroxide on serum lipoproteins in hypercholesterolemic adults. RESULTS: The results of the trial, which was conducted on two Israeli kibbutzim (rural cooperative communities), have been published previously. CONCLUSIONS: The kibbutz presents a unique setting for the conduct of a clinical trial. There were opportunities to uphold inclusion and exclusion criteria carefully, to obtain informed consent, to enhance dietary and drug adherence, to ensure the quality of data collection, to maintain the interest of the participants in the study, and to monitor closely adverse effects and patient safety. This report describes the unique circumstances under which the trial was conducted and the role of the clinician as a clinical investigator and discusses their implications for the internal validity and generalizability of the trial.

The relationship between plasma and dialysate lipoproteins and apoproteins in patients treated by continuous ambulatory peritoneal dialysis.

End-stage renal disease is frequently associated with lipoprotein abnormalities, manifested primarily by elevated very low-density lipoprotein levels combined with a decrease in high-density lipoprotein levels. These lipoprotein disturbances are further exacerbated in continuous ambulatory peritoneal dialysis. We examined the lipoprotein and apolipoprotein profiles in the blood and dialysate effluents of eight normolipidemic and five hypertriglyceridemic patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis. The normolipidemic patients were found to have significantly greater losses, as expressed by the fractional catabolic rates through the dialysate, for protein, total cholesterol, and very low-density lipoprotein cholesterol. These results suggest that the hypertriglyceridemia associated with continuous ambulatory peritoneal dialysis may be mitigated in some patients by the excessive loss of very low-density lipoprotein, or some other plasma constituent, into the dialysate effluent.

Thyroid function and other clinical chemistry parameters in subjects eating iodine-enriched eggs.

Iodine-enriched (IE) eggs are produced by chickens fed a diet containing kelp. These eggs, which contain an average of 711 micrograms iodine/egg, have been reported to reduce plasma cholesterol in humans and laboratory animals. A modified form of these eggs is under consideration for marketing in the United States. 104 hyperlipidaemic subjects were placed on a low-fat diet for 12 wk. Between wk 4 and 12, approximately half of the subjects were randomized to a dietary control group (n = 53) or a group who ingested one IE egg/day in addition to this diet (n = 51). Some subjects in both groups continued in the study for an additional 4-8 wk. No significant adverse clinical effects were observed or reported, with the exception of one subject who reported an allergic-like reaction soon after beginning egg ingestion. All clinical chemistry values remained within normal limits, and comparisons between the egg group and controls were not significant. Three subjects (two in the egg group and one in the control group) had elevated thyroid stimulating hormone levels during the experimental period. All thyroid function tests remained within normal limits in the remaining subjects. Thus, ingestion of one IE egg of the type used in our study appears to be relatively safe and devoid of clinically significant, short-term adverse effects in healthy individuals.

Plasma lipoproteins in hyperlipidemic subjects eating iodine-enriched eggs.

Iodine-enriched (IE) eggs are produced by chickens fed a diet containing kelp. These eggs have been reported to reduce plasma cholesterol in humans and experimental animals. The purpose of this study was to determine the effect of the ingestion of one IE egg/day on the plasma lipoprotein cholesterol in borderline and hyperlipidemic individuals ingesting a low-fat diet. One hundred three subjects with entry cholesterol levels greater than 5.17 mmol/L were placed on a low-fat, low-cholesterol diet for 12 weeks. Between weeks 4 and 12, approximately half of the subjects were randomly assigned to either a diet control group (n = 53), or a group who ingested one IE egg/day in addition to this diet (n = 50). Subjects in both the egg group and the diet control group had a significant reduction in total plasma cholesterol (TC) at the end of the study compared with study entry; addition of the egg in the diet did not abolish the TC reduction in the egg group. However, paired comparisons of total and lipoprotein cholesterol levels at the end of the egg intervention period with the end of the initial dietary period demonstrated that the egg group had a significantly greater increase than the diet control group in TC (egg group: 7.2 +/- 1.5% increase; diet controls: 1.5 +/- 0.9% increase; p less than 0.01) and low-density lipoprotein cholesterol (egg group: 9.2 +/- 1.7% increase; diet controls: 3.9 +/- 1.5% increase; p less than 0.01). This effect was most pronounced in subjects with higher initial cholesterol levels and subjects with mixed hyperlipidemia (elevated cholesterol and triglyceride). Results suggest that these particular groups of subjects are most susceptible to cholesterol changes associated with ingestion of IE eggs.

Saturated fats, cholesterol, and dietary compliance.

BACKGROUND: Lack of response to a cholesterol-lowering diet can be caused by physiological nonresponsiveness, inadequate knowledge, or inability to change dietary habits (poor compliance). The purpose of this study was to evaluate the dietary compliance of hyperlipidemic individuals who received intensive initial dietary education and followup, and who showed an initial reduction of their plasma cholesterol levels. METHODS: One hundred five individuals with fasting cholesterol levels of 5.17 mmol/L (200 mg/dL) or greater received intensive education and follow-up on the American Heart Association Step I diet during an initial 12-week period. The participants provided 3-day dietary records every week, and fasting lipoprotein analysis was performed biweekly. Six months after termination of this period, the subjects were requested to return for a follow-up evaluation of their lipoprotein profile and dietary adherence. RESULTS: Seventy-three (70%) of the subjects returned for a follow-up evaluation of lipoprotein cholesterol levels. Of these, 42 (58%) had a 10% or greater average initial decrease in total cholesterol levels at weeks 3 and 4 ("baseline"), and they were considered to be "high responders." At the 6-month follow up, the average plasma cholesterol level in these responders remained 6.4% below that at entry level, but it had increased by 19% compared with baseline values (6.30 mmol/L [244 mg/dL] vs 5.43 mmol/L [210 mg/dL], respectively). Corresponding significant increases at 6 months were found in high-density lipoprotein cholesterol (8%), low-density lipoprotein cholesterol (16%), and very-low-density lipoprotein cholesterol (66%) levels. Analysis of dietary histories revealed that dietary cholesterol and percent calories from fat increased significantly, but remained within the recommended guidelines. However, the increase in percent calories from saturated fat (from 10.0% +/- 0.5% to 14.4% +/- 1.0% [mean +/- SEM]) deviated markedly from these guidelines. CONCLUSIONS: The results suggest the long-term compliance to the reduction of dietary saturated fat remains a problem, even in individuals who receive intensive initial training and show an early favorable response. Follow-up evaluation of hyperlipidemic patients who are receiving dietary therapy should take into account this behavioral pattern. It remains to be determined whether continuing supervision and better nutritional labeling will facilitate dietary compliance.

Secondary dyslipidemia. Inadvertent effects of drugs in clinical practice.

OBJECTIVE: To examine the available literature on commonly prescribed drugs and their effects on blood lipid and lipoprotein levels. DATA SOURCES: The review was based on searches of English-language articles from 1975 to 1990 by Medlars II and MEDLINE programs, the Index Medicus for 1980 to 1990, and references from identified articles. Relevant journals published within the last 6 months were also examined. STUDY SELECTION: More than 500 articles were identified for inclusion. Articles were selected on the basis of appropriateness of design to demonstrate significant results, determined by consensus when necessary. DATA EXTRACTION: Studies were classified according to type (observational or interventional), length of follow-up, and type of controls. Quanitative analysis of lipid, lipoprotein, and apoprotein changes induced by drugs was computed as the percentage of change observed during the course of the study (interventional) or compared with the controls at a given time (observational). DATA SYNTHESIS: Steroid hormones that have strong progestogenic and androgenic properties, retinoids, cyclosporine A, and phenothiazines are potentially atherogenic. Steroid hormones with dominant estrogenic properties, several anticonvulsants, biguanides, high-dose ketoconazole, and aminosalicylic acid are potentially antiatherogenic. Corticosteroids appear to elevate all the lipoprotein cholesterol levels. Oral estrogens, retinoids, and corticosteroids also can elevate triglyceride levels. Other drugs with questionable effects on lipoprotein metabolism are reviewed. CONCLUSION: Although the long-term implications of drug-induced lipoprotein changes are still undefined, physicians need to consider these effects in clinical practice.

The hypocholesterolemic effect of an antacid containing aluminum hydroxide.

STUDY OBJECTIVE: To evaluate the efficacy, safety, and hypocholesterolemic effect of an aluminum hydroxide-containing antacid in hypercholesterolemic individuals. DESIGN: A prospective, randomized, double-masked, placebo-controlled phase of 2 months' duration, followed by an open-design treatment phase of 2 months' duration and a washout phase of 2 months' duration. SETTING: Family practice clinics of two rural communities (kibbutzim) in Israel. PATIENTS: Fifty-six men and women with hypercholesterolemia (type IIa or IIb). Fifty individuals completed the study. INTERVENTION: After 2 months of dietary modification (low-fat, low-cholesterol diet), the participants were randomized into two matched groups. Group 1 (28 participants) was treated for 2 months with a chewable antacid tablet containing simethicone, magnesium hydroxide, and 113 mg of aluminum hydroxide per tablet, at a dose of two tablets four times daily. Group 2 (22 participants) was given a similar number of placebo tablets for 2 months. During the following 2 months, both groups received the antacid at the above dose. MEASUREMENTS AND MAIN RESULTS: Lipoprotein levels were evaluated at baseline and every 2 months thereafter for 6 months. Compared with pretreatment levels, Group 1 experienced a decrease in low-density lipoprotein cholesterol (LDL-C) of 9.8% after 2 months (p less than 0.001) and 18.5% after 4 months (p less than 0.001). Compared with Group 2, the decrease in LDL-C in Group 1 was 6.2% at the end of the 2-month double-masked, placebo phase. Although the high-density lipoprotein cholesterol (HDL-C) was also reduced in Group 1 at the end of 4 months of therapy (10.2%), the HDL-C/LDL-C ratio increased by 13% during the same interval (p less than 0.05). The treatment was well tolerated, with minimal side effects. CONCLUSIONS: An aluminum hydroxide-containing antacid reduces LDL-C in hypercholesterolemic individuals. Although HDL-C was also reduced to a lesser extent, the overall atherogenic index was improved. Further studies should be conducted to evaluate the long-term safety and efficacy of antacids containing aluminum hydroxide in hypercholesterolemic patients.

Niacin revisited: clinical observations on an important but underutilized drug.

STUDY OBJECTIVE: To evaluate the efficacy and side effects of niacin therapy in dyslipidemic individuals. DESIGN: A retrospective analysis of patients' charts. SETTING: An outpatient referral-based clinic specializing in the treatment of lipid disorders. PATIENTS: All patients with dyslipidemia treated by niacin (n = 82) at the Atherosclerosis Detection and Prevention Clinic during 1987 to 1990, including a subgroup of 17 dyslipidemic heart transplant recipients. RESULTS: Niacin was well tolerated in 83% of the nontransplant group (n = 65) at an average dose of 2.5 +/- 0.9 g/day. Similar beneficial lipoprotein effects were found in the transplant and nontransplant patients. The high-density lipoprotein cholesterol (HDL-C) response to niacin therapy was independent of the baseline (HDL-C level. In the transplant group, 11 patients (65%) discontinued treatment, primarily because of hyperglycemia; this was especially prominent in those patients with pretreatment diabetes mellitus. Of the 15 patients using sustained-release niacin, eight cases of hepatitis were recorded, some during therapy with relatively low niacin doses. Several different sustained-release preparations were responsible for this phenomenon, suggesting that the cause was not a contaminant in the preparation. No cases of hepatitis were documented in the 67 patients using regular niacin. One case of hepatitis was recently observed in a patient who switched from one type to regular niacin to another; however, we have data to suggest that the substituted preparation was not an immediate-release niacin. A familial predisposition to hepatitis is suggested by the occurrence of this side effect in identical twin brothers and two sisters. A pharmacy survey disclosed that most pharmacists are unaware of the relationship of sustained-release niacin to hepatitis, have a negative impression of regular niacin, and do not stock this formulation. Finally, we found that in this small sample of patients, niacin used with lovastatin is a particularly effective drug combination and appears to have few side effects beyond those seen with niacin alone. CONCLUSIONS: Our experience supports the fact that regular niacin is a useful lipid-modifying drug. When used appropriately, patients can usually tolerate adequate doses for prolonged periods and achieve meaningful results. However, this requires a certain amount of physician skill and patient motivation. The use of sustained-release preparations to overcome this problem can lead to harmful consequences and should only be done under strict medical supervision. In our opinion, the availability of sustained-release niacin as a nonprescription drug is unjustified and should be reexamined. Finally, we have observed that reduction of very-low-density lipoprotein cholesterol (VLDL-C) with niacin alone leads to an elevation in low-density lipoprotein cholesterol in many patients; this indicates to us that the mechanism whereby niacin lowers VLDL-C and total cholesterol is not solely the result of a decreased synthesis of VLDL-C.

Sedation effect on temporary threshold shift induced by acoustic overstimulation.

The mechanism by which noise damages the inner ear has not as yet been fully elucidated. Experiments were done to study the influence of the sedation in temporary threshold shift (TS) induced by acoustic overstimulation, as barbiturates were found to improve the brain's tolerance to ischemia. Four groups of guinea pigs (GP) were used. The temporary TS was decreased with the reduction of the temperature in awake, as well as sedated, sound-exposed GP. However, the temporary TS in the sedated, but normothermic GP was as great as in the awake, normothermic group. The high temperature counteracts the protection effect of the sedation in nose-induced hearing loss.