PubMed HealthSearch

Biomedical subjects

R Jacob

Publications and source records attributed to R Jacob.

At least 73 records · Page 4Linked to original sources

n-3 versus n-6 fatty acid incorporation into the phospholipids of rat heart sarcolemma. A comparative study of four different oil diets.

The fatty acid (FA) composition of the phospholipids of rat heart sarcolemma was studied after a 10-week feeding period of diets containing 10% of each of coconut oil, corn oil, linseed oil, and fish oil in comparison to a low fat diet. The major modifications observed were the following: (1) a general increase of the n-6 FA family upon corn oil administration; (2) a dual effect of linseed oil in increasing 18:2 n-6 (more than did corn oil) and decreasing 20:4 n-6 and 22:4 n-6. At the same time n-3 FA increased significantly; and (3) a significant fall in the n-6 FA following fish oil, and a marked rise in the n-3 FA. The 10-fold increase in 22:6 n-3 supports the hypothesis of an inhibition of arachidonate synthesis, as well as that of the competition for the incorporation sites of phospholipids. In general, the n-3 FA diets produced the replacement of the n-6 FA by the n-3 FA in membrane phospholipids, and led to a significant increase of the double bond index (DBI).

Animals

Efficacy of low-dose epidural anaesthesia in surgery of the anal canal--a randomised controlled trial.

The aim of the study was to compare in terms of patient comfort, surgical requirements and anaesthetic safety, the difference between epidural and general anaesthesia in patients undergoing surgery of the anal canal. The study was undertaken on 50 adult patients undergoing anal surgery. By random allocation 25 were given a general anaesthetic while 25 were given a low-dose epidural using 0.375% bupivacaine. Advantages and disadvantages of both methods were noted in the study. It was concluded that low-dose epidural is a more effective means of providing analgesia, while maintaining adequate sphincter tone for surgery on the anal canal, than general anaesthesia.

Adolescent

Differential effects of various oil diets on the risk of cardiac arrhythmias in rats.

BACKGROUND: Independently of the problem of atherogenesis, the amount and type of fat intake influences the risk of cardiac arrhythmias. However, the relative effectiveness of different fats and the underlying mechanisms are controversial. The aim of the present study was to compare the effects of various oil-enriched diets on the risk of ventricular arrhythmias in rat hearts under conditions of ischaemia and reperfusion and to help clarify the mechanisms underlying the differing effects of the oils on the occurrence of arrhythmias. METHODS: Over a 10-week period, we studied five groups of young male Wistar rats given a low-fat chow diet or one enriched with 10% hydrogenated coconut oil, corn oil, linseed oil or sardine oil. Electrocardiograms were recorded from the isolated hearts (Langendorff preparation) perfused with a modified Krebs-Henseleit solution. Ischaemia was induced by a 20 min occlusion of the left anterior descending coronary artery. In another series of experiments, a 10 min occlusion was followed by a 20 min reperfusion period. The times between the first occurrence of extrasystole and the incidence of ventricular tachycardia and fibrillation were determined. The size of the ischaemic zone was assessed using malachite green. The fatty acid composition of the myocardial tissue was analysed using gas chromatography. RESULTS: An increase in the risk of ventricular arrhythmias under conditions of both ischaemia and reperfusion was obvious in the rats that consumed large quantities of saturated fatty acids (coconut oil) and in the group with a very low intake of fat. Polyunsaturated fatty acids (PUFAs), particularly fish oil, exerted a protective effect. The incidence of ventricular fibrillation was 75% in the low-fat group, 67% in the coconut-oil group, 44% in the corn-oil group, 40% in the linseed-oil group and 10% in the fish-oil group. The time until the first occurrence of extrasystole, the incidence of ventricular tachycardia and the incidence of reperfusion-induced ventricular fibrillation were influenced in a similar manner. The size of the ischaemic zone was significantly reduced in the groups given diets enriched with PUFAs. All protective effects were abolished, however, by cyclooxygenase inhibition with aspirin. The fatty acid composition of myocardial tissue, the ratio of n-3 to n-6 fatty acids and the double-bond index were significantly affected by the various diets. CONCLUSION: Whereas saturated fatty acids are obviously proarrhythmic, diets enriched with n-6 or n-3 PUFAs both exert antiarrhythmic effects. Although n-3 fatty acids seem to be more effective, cardioprotection cannot simply be related to the replacement of n-6 by n-3 fatty acids in cardiac membrane phospholipids, given the beneficial effects of corn oil. In any case, replacement of n-3 by n-6 fatty acids is not the underlying mechanism. The overall reduction of prostaglandin formation cannot be the primary mechanism because the beneficial effects of diets rich in PUFAs were abolished by cyclooxygenase inhibition. We conlcude that, besides prostacyclin (PGI2 or PGI3), membrane fluidity and accompanying alterations in functional membrane proteins (e.g. protection from calcium overload) are key factors apart from vascular effects that influence the size of the ischaemic zone.

Animals

Effectiveness of garlic on the radical activity in radical generating systems.

The radical scavenging capacity of garlic (allium sativum) has been investigated in vitro in radical generating systems by electron paramagnetic resonance (EPR) and low-level chemiluminescence measurements. Garlic (both the homogenate of 10% in physiological saline solution and its supernatant) was able to reduce the radicals generated by the Fenton reaction and trapped by phenyl-butyl-nitron for EPR measurements. Also radicals present in cigarette smoke could be reduced by garlic as judged from chemiluminescence in the presence of tert.-butyl-hydroperoxide. According to the in vitro measurements garlic contains substances which have significant radical scavenging capacity.

Cyclic N-Oxides

Cardioprotective actions of wild garlic (allium ursinum) in ischemia and reperfusion.

The susceptibility to ventricular arrhythmias under the conditions of cardiac ischemia and reperfusion was investigated in the Langendorff heart preparation of rats fed for eight weeks a standard chow enriched with 2% of pulverized wild garlic leaves. The isolated hearts were perfused with a modified Krebs-Henseleit solution. The incidence of ventricular fibrillation (VF) during 20 min occlusion of the descending branch of the left coronary artery (LAD) was significantly reduced in the wild garlic group as compared to untreated controls (20% vs 88%). The same holds for the size of the ischemic zone (33.6% vs 40.9% of heart weight). In the reperfusion experiments (5 min after 10 min ischemia), ventricular tachycardia (VT) occurred in 70% of the wild garlic group vs 100% in untreated controls and VF in 50% vs 90%. The time until occurrence of extrasystoles, VT or VR was prolonged. No significant alterations in cardiac fatty acid composition could be observed. Although the prostacyclin production was slightly increased in hearts of the wild garlic group, inhibition of cyclooxygenase by acetylsalicylic acid (ASA; aspirin) could not completely prevent the cardioprotective effects suggesting that the prostaglandin system does not play a decisive role in the cardioprotective action of wild garlic. Furthermore, a moderate angiotensin converting enzyme (ACE) inhibiting action of wild garlic was found in vitro as well as in vivo that could contribute to the cardioprotective and blood pressure lowering action of wild garlic. Whether a free radical scavenging activity of wild garlic is involved in its cardioprotective effects remains to be established.

Angiotensin-Converting Enzyme Inhibitors

Zonisamide for add-on treatment of refractory partial epilepsy: a European double-blind trial.

The new antiepileptic drug zonisamide was evaluated in a European multicenter parallel-group double-blind trial as add-on treatment for 139 patients with refractory partial epilepsy. During treatment with zonisamide complex partial seizures decreased by 27.7% compared to placebo (P < 0.05) and the median rate dropped from 12/month to 7.1/month with no changes in the placebo group (P < 0.007). During the 12-week double-blind phase a 50% reduction of all seizures was recorded in 29.9% of the patients treated with zonisamide vs. 9.4% during placebo. Complete remission was observed during treatment with zonisamide in 6.2%. The plasma concentrations of the concomitant antiepileptic drugs did not change markedly when zonisamide was added. Adverse events, mostly fatigue, somnolence, dizziness and ataxia, occurred in 59.2% of the patients compared to 27.9% during placebo. Zonisamide was withdrawn in two patients due to adverse events. Kidney stones were not observed nor any relevant clinical chemistry or hematological changes. Zonisamide is an effective antiepileptic drug for add-on treatment of refractory partial epilepsy.

Adolescent

Assessing technology assessment. Early results of the Quebec experience.

The Quebec Council on Health Care Technology Assessment was created in 1988. Its functions are to promote, support, and produce health care technology assessments and to advise the Minister of Health. An independent review of the council's first four years of operation was commissioned. The evaluation team concluded that the council showed very good results in terms of the scope, quality, and impact of its production and succeeded in establishing its credibility. However, the evaluation team suggested that the council adopt a more active strategy toward the promotion and diffusion of its reports. Some critical determinants of success of the Quebec experience in technology assessment are discussed.

Diffusion of Innovation

A comparison of caudal epidural bupivacaine with adrenaline and bupivacaine with adrenaline and pethidine for operative and postoperative analgesia in infants and children.

This study compares the effectiveness of two drug combinations--(a) bupivacaine with adrenaline and (b) bupivacaine with adrenaline and pethidine--on operative and postoperative pain relief when administered by the caudal route in infants and children. A randomised controlled trial was conducted on fifty children below the age of twelve years: 25 children were randomly allocated to each group. Both groups had a significant period of analgesia in the postoperative period. None of the children in either group required parenteral analgesia. Though the group with pethidine had a longer duration of analgesia and sedation, the very high incidence of vomiting and delay in urination observed in this group would preclude the use of pethidine routinely. No respiratory depression was seen in either group.

Analgesia, Epidural

Glucose metabolism during the menstrual cycle. Assessment with the euglycemic, hyperinsulinemic clamp.

To assess tissue sensitivity to insulin during the follicular and luteal phases of the menstrual cycle, two-step euglycemic, hyperinsulinemic clamp studies in combination with tritiated glucose infusion and indirect calorimetry were performed in regularly menstruating women in randomized order. There was no difference in the basal follicular and luteal phase levels of glucose, insulin or glucose turnover. A low-dose (0.25 mU/kg/min) insulin infusion suppressed endogenous hepatic glucose production. There was no difference in tissue insulin sensitivity during a high-dose insulin infusion (1.0 mU/kg/min). Nonoxidative glucose disposal also was similar in the basal and insulin infusion periods. Under euglycemic, hyperinsulinemic conditions, there is no difference in tissue sensitivity to insulin, and intracellular pathways of glucose disposal are not altered by the stage of the menstrual cycle.

Adult

Cardioprotective actions of garlic (Allium sativum).

The influence of an intake of garlic powder (1%--corresponding to Kwai/Sapec--added to a standard chow for a 10-week period) on the susceptibility to ventricular arrhythmias under ischemia and reperfusion was investigated in the isolated rat heart (Langendorff preparation) perfused with a modified Krebs-Henseleit solution. The incidence of ventricular tachycardia (VT) and fibrillation (VF) after ligation of the descending branch of the left coronary artery (LAD) (20 min) was significantly reduced in the garlic group as compared to untreated controls (VT: 0% vs. 35.5%; VF: 50% vs. 88%). The size of the ischemic zone was significantly smaller (31.7% vs. 40.9% of total heart tissue). The reperfusion experiments (5 min after 10 min ischemia) revealed similar results (VT: 50% vs. 100%; VF: 30% vs. 90%). The time until occurrence of extrasystoles and VT or VF was prolonged in most cases, and the duration of arrhythmias was abbreviated. No significant alterations in cardiac membrane fatty acid composition could be found. Inhibition of cyclooxygenase by acetylsalicylic acid (ASA) caused a moderate increase in arrhythmias and ischemic zone in the garlic group as well as in untreated controls under the conditions of the present experiments. Thus, it seems that the prostaglandin system does not play a predominant role in the cardioprotective action of garlic. The significance of free radical scavenging activity of garlic for its antiarrhythmic effects has to be established.

Animals

[How reliable is oscillometric blood pressure determination at the finger using the Omron device?].

The precision of oscillometric blood-pressure measurements on the finger with the model HEM-812F, manufactured by Omron, was compared to the standard method. The digital measurements from 180 inpatients (115.0 +/- 1.2 mmHg systolic, 68.8 +/- 0.8 mmHg diastolic) were significantly lower than oscillometric measurements from the upper arm using a Bosomat (121.3 +/- 1.4 mmHg systolic, 74.2 +/- 0.9 mmHg diastolic). Correlation coefficients were r = 0.713 for systolic and r = 0.683 for diastolic values, with significant variance of individual values. In direct comparison of the two methods immediately after ergometry the differences were even greater (57 mmHg systolic, 32 mmHg diastolic). Significantly lower digital pressures at the finger were noted in comparison with direct blood-pressure measurements after punction of the femoral artery. Because of significant differences of blood-pressure measurements compared to the Riva-Rocci method, the digital measurement with the HEM-812F device (Omron) can not be generally recommended.

Blood Pressure Determination

Structural and functional diversity of human ventricular myosin.

The role of subcellular alterations in the process of heart failure remains ill-defined. Because contractile performance of failing heart muscle is depressed, possible alterations in the myosin molecule could be of particular relevance. There is increasing evidence that myofibrillar ATPase activity is reduced in congestive heart failure, whereas the findings on myosin ATPase are still controversial. The molecular causes of the reduced activity are currently not known. Because alpha-MHC is present only in small amounts in normal ventricles, a shift in favor of beta-MHC is of minor importance. Also immunohistochemical data on subspecies of beta-MHC seem not to provide an explanation. A new type of myosin heterogeneity was found by optimizing native polyacrylamide gel electrophoresis in the presence of pyrophosphate. Two bands (VA and VB) were observed in ventricles of patients with valvular disease. Because the two bands were detected also in normal hearts of large mammals, the existence of VA/VB cannot be diagnostic of diseased heart. However, the VA/VB ratio was influenced by the hemodynamic load, whereby the fast migrating band (VA) increased with the diastolic and systolic load. Because a relationship with the hemodynamic load was observed only in surgical muscle specimens, it appears that this heterogeneity is prone to post mortem modification. Further work is required to identify the molecular nature of this heterogeneity and to examine the therapeutic potential of a pharmacological modification of the VA/VB ratio.

Adult

Metabolically-modulated growth and phenotype of the rat heart.

Heart muscle reacts to work overload and various neuroendocrine stimuli by inducing myocyte growth. A novel type of hypertrophy can be induced in the rat heart by etomoxir, which reduces fatty acid oxidation. This hypoglycaemic drug inhibits the mitochondrial carnitine palmitoyltransferase 1, and thus reduces the long-chain fatty acid uptake of mitochondria; in a compensatory manner, the glycolytic flux is enhanced. In rats, etomoxir induced a harmonious growth of the left and right ventricles of normal and pressure-overloaded hearts. To characterize the protein phenotype, myosin expression and sarcoplasmic reticulum (SR) Ca2+ pump activity were determined. In contrast to pressure-overloaded hearts, etomoxir increased the proportion of myosin V1, Ca(2+)-stimulated SR ATPase activity and the rate of SR Ca2+ uptake. Since etomoxir did not increase blood pressure, heart rate or circulating thyroid hormones, it appears that established mechanisms of other models of cardiac hypertrophy were not involved. The etomoxir-induced changes thus seem closely linked to the shift in energy metabolism.

Animals

Functional significance of the Frank-Starling mechanism under physiological and pathophysiological conditions.

The functional significance of the Frank-Starling mechanism under physiological and pathophysiological conditions is discussed, based mainly on animal experiment results (in the dog, pig and rat). The dependence of individual stroke volume on end-diastolic volume can be described adequately using Frank's diagram. This can be illustrated by varying filling pressure (respiratory cycle, vascular tone in the capacitance system, body position, circulating blood volume) and by alterations in the duration of the filling period (heart rate and rhythm, rate of relaxation) and in ventricular compliance (wall thickness, fibrosis; contracture, rigor). The functional importance of the Frank-Starling mechanism lies mainly in adapting left to right ventricular output. During upright physical exercise an increase in end-diastolic volume due to the action of the peripheral muscle pump and increased venous tone can assist in enhancing stroke volume. Reduced contractility leads to a shift of the operating point to the right in the pressure-volume diagram, thus tending to prevent a decrease in stroke volume. However, the consequences of increased circulating blood volume in chronic heart failure are, as a rule, mainly detrimental (congestive symptoms; myocardial component of coronary resistance; cardiac energetics). Reduced contractility results in a flattening of the relation between stroke volume (or stroke work) and end-diastolic volume. Furthermore, the Starling mechanism is prevented from becoming effective if the sarcomere-length reserve is exhausted, or in the presence of inadequate sarcomere extension due to impaired relaxation or reduced distensibility of the ventricular wall. The latter is illustrated using the example of a dilated fibrotic left ventricle from a rat with experimental supravalvular aortic stenosis.

Animals

Swimming changes vascular fatty acid composition and prostanoid generation of rats.

To define the effects of physical activity on vascular fatty acid composition and prostanoid generation, spontaneously hypertensive and normotensive rats were made to swim at 34-35 degrees C for 5-7 wk. Fatty acids were determined by gas chromatography and prostanoids by high-performance liquid chromatography and electrochemical detection. A characteristic feature of swimming rats was a markedly reduced linoleic acid content in the iliac artery and the aorta; in normotensive swimming rats stearic acid and arachidonic acid contents were increased. These changes could not be attributed to a heat loss during swimming or to depressed growth characteristics. A chemical sympathectomy using guanethidine (60 mg/kg body wt daily) did not prevent the alterations in fatty acid composition. A higher arachidonic acid content was correlated with an increased generation of 6-ketoprostaglandin F1 alpha in the aorta of untreated rats and sympathectomized rats. It is concluded that swimming can alter the vascular fatty acid composition in a manner which results in an increased potential for prostacyclin production.

Animals

Functional results after total or near total glossectomy with laryngeal preservation.

Locally advanced tongue cancer is a devastating disease for which there are limited therapeutic options that will result in a high rate of cure while preserving function. To determine the oncologic effectiveness of total or near total glossectomy with laryngeal preservation and the possibility of speech and swallowing rehabilitation following treatment, we reviewed our experience with 27 patients treated between 1982 and 1989. Twenty-four patients were eligible for 2-year follow-up and their disease-specific survival was 51%. Swallowing was achieved initially in 18 patients (67%), while 12 had successful long-term deglutition (44%). Oral communication was accomplished in 25 patients (92%). Significant aspiration occurred in three patients and was severe enough to require interval laryngectomy in two patients. The role of laryngeal suspension, palatal augmentation prosthesis, and videofluoroscopy as rehabilitation adjuncts for the total glossectomy patient are described.

Adult

The functional ambivalence of adaptive processes--considerations based on the example of the hemodynamically overloaded heart.

Cardiac hypertrophy and neuro-humoral reactions in hemodynamic overload are employed as examples to show that adaptive processes, while in principle enabling the whole organ to cope with increased load, as a rule also include unfavorable components. This is primarily due to competition between different demands with respect to, for instance, mechanical or energetic parameters. An impressive demonstration of the ambivalence of adaptive processes can be seen in the functional consequences of myocardial mass increase, eccentric configurational changes, and the alteration of the myocardium towards a "slower muscle". It can be demonstrated that, due to structural modifications in the heart, unfavorable effects occur at the level of the whole organ as well as in macromolecular dimensions from the very beginning, and not only as a consequence of qualitatively and quantitatively inappropriate adaptation. Thus, a clear-cut distinction between "physiological" and "pathological" processes is almost impossible. In the clinic, the unfavorable effects of the process of hypertrophy are often emphasized and the reduction of hypertrophy is declared the principal therapeutic aim. However, in the individual case the extent to which vascular alterations participate in, or are even mainly responsible for the unfavorable effects occurring in pressure hypertrophy should be clarified. In any case, reduction of hemodynamic overload should be the focus of therapeutic concern.

Adaptation, Physiological

Electrocautery does not interfere with the function of the automatic implantable cardioverter defibrillator.

The automatic implantable cardioverter defibrillator (AICD) manufactured by Cardiac Pacemakers, Inc, contains an automatic sensitivity adjustment. We tested whether this feature would prevent sensing of signals generated by electrocautery by implanting three different models of the AICD in 4 mongrel dogs. Unipolar electrocautery was applied at maximum output to a site close to the rate-sensing leads. The devices were monitored with an AICD-check probe and by auditory monitoring of QRS synchronous tones. No sensing of the electrocautery by the device occurred. Three patients with two different AICD models (1550 and 1520) underwent five surgical procedures in which electrocautery was used. No sensing of electrocautery signals, device charging, or other device malfunction occurred.

Animals