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Biomedical subjects

R Jacob

Publications and source records attributed to R Jacob.

At least 19 recordsLinked to original sources
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Opiate blockade enhances hypoglycemic counterregulation in normal and insulin-dependent diabetic subjects.

To examine the impact of opiate blockade on glucose counterregulation we performed two hypoglycemic insulin clamp studies with and without naloxone in healthy subjects and well-controlled insulin-dependent (IDDM) patients with defective glucose counterregulation. During both studies plasma glucose fell to 55-60 mg/dl and was then maintained at that level using a variable glucose infusion. In normal subjects, naloxone increased glucose production, thereby reducing the exogenous glucose dose needed to maintain the hypoglycemic plateau. Epinephrine and cortisol responses to hypoglycemia were increased during naloxone plus insulin compared with insulin alone; glucagon responses were unaffected. IDDM patients with suppressed hepatic and hormonal responses to insulin-induced hypoglycemia also demonstrated greater stimulation of glucose production as well as epinephrine, growth hormone, and cortisol release during the naloxone study. In the absence of hypoglycemia, naloxone did not significantly affect glucose production or glucoregulatory hormones. We conclude that opiate blockade augments glucoregulatory responses to insulin-induced hypoglycemia, even in IDDM patients with preexisting defects in glucose counterregulation. This effect is at least in part due to enhanced counterregulatory hormone release during hypoglycemia. Endogenous opiates may modulate hormonal responses during hypoglycemia; their blockade could provide a means of ameliorating defective counterregulation in IDDM patients.

Adult↗
PubMed1991

Functional consequences of cardiac hypertrophy and dilatation.

Based on animal experiments in rats (spontaneous and renal hypertension, experimental aortic stenosis, thyroxine and training-induced hypertrophy, and aorto-caval fistula with and without additional unilateral renal artery coarctation) as well as clinical data and literature, the functional consequences of cardiac hypertrophy and structural ventricular dilatation are analyzed and discussed. A methodological approach, developed on the basis of Frank's diagram and model calculations, permits quantitatively estimating the significance of ventricular geometry (wall thickness and inner dimensions) compared to myocardial alterations (decrease in contractility and distensibility) and hemodynamic load (preload and systolic pressure). As a rule, hypertrophy causes an increase in ventricular working capacity, which allows the heart to cope with an increased hemodynamic load without a decrease in stroke volume and without enhanced systolic stress requirement. Adverse consequences mainly concern ventricular compliance, cardiac energetics, and electrophysiological parameters. Particularly from the example of the aorto-caval fistula, it can be seen that enhanced systolic wall stress does not necessarily lead to heart failure within a few months. However, the length of time for which the additional wall stress, with correspondingly increased energy demand, can be tolerated remains to be determined. In later stages, a multitude of alterations on the cellular, tissue, and organ level occurs, affecting myocardial and ventricular mechanics and energetics, depending on the type, velocity of development, and duration of overload. A distinction should be made between the adverse alterations, which can be related to myocardial growth, and those that are not necessarily related to a certain cell size (receptors, transformation of the contractile proteins) as well as those changes that do not primarily influence the myocardial cell (arteriosclerosis, microangiopathy). Structural dilatation alone could lead to insufficiency only in the case of substantial increase in inner ventricular radius. Reduced contractility, myocardial distensibility, and increased pressure load aggravate the negative effects of dilatation in a predictable manner, as demonstrated on the basis of a representative case of dilative cardiomyopathy. Using the example of spontaneously hypertensive rats, it is shown that ventricular mass and shape are differently influenced by various blood-pressure lowering agents, e.g., atenolol, nifedipine, and dietary interventions. It is concluded from the analysis of chronic cardiac reactions that adaptive processes are, in principle, ambiguous in character, revealing negative components even in the case of regular adaptation. However, it seems unjustified to aim at a regression of hypertrophy without reducing the underlying hemodynamic overload.

Adaptation, Physiological↗
PubMed1990

Homologous desensitization of ATP-mediated elevations in cytoplasmic calcium and prostacyclin release in human endothelial cells does not involve protein kinase C.

Single human umbilical-vein endothelial cells in culture loaded with the Ca2(+)-sensitive dye fura-2 exhibited characteristic increases in cytosolic Ca2+ concentrations [( Ca2+]i) in response to extracellular ATP. The rapid decline of [Ca2+]i to prestimulated levels in the continued presence of ATP, with in most cells no sustained or oscillatory increase in [Ca2+]i, indicated desensitization. This was agonist-specific, and contrasted with the [Ca2+]i response to histamine, though each agonist mobilized Ca2+ from the same internal store. In populations of cells, when desensitization was variably induced by a second challenge with ATP after different times, desensitization of the initial peak [Ca2+]i was directly related to desensitization of prostacyclin release. This was not affected by treatment with the protein kinase C inhibitor staurosporine, under conditions where a similar degree of desensitization of peak [Ca2+]i induced by phorbol 12-myristate 13-acetate was blocked. Sequential addition of ATP to cell populations cumulatively desensitized the peak elevation of [Ca2+]i, but did not block the second, sustained, phase of the response. We conclude that desensitization of prostacyclin synthesis by ATP is likely to be due to uncoupling of the P2Y purinoceptor from phosphoinositidase C, but does not involve protein kinase C activation.

Adenosine Triphosphate↗
PubMed1990

SK&F 96365, a novel inhibitor of receptor-mediated calcium entry.

A novel inhibitor of receptor-mediated calcium entry (RMCE) is described. SK&F 96365 (1-(beta-[3-(4-methoxy-phenyl)propoxy]-4-methoxyphenethyl)-1H- imidazole hydrochloride) is structurally distinct from the known 'calcium antagonists' and shows selectivity in blocking RMCE compared with receptor-mediated internal Ca2+ release. Human platelets, neutrophils and endothelial cells were loaded with the fluorescent Ca2(+)-indicator dyes quin2 or fura-2, in order to measure Ca2+ or Mn2+ entry through RMCE as well as Ca2+ release from internal stores. The IC50 (concn. producing 50% inhibition) for inhibition of RMCE by SK&F 96365 in platelets stimulated with ADP or thrombin was 8.5 microM or 11.7 microM respectively; these concentrations of SK&F 96365 did not affect internal Ca2+ release. Similar effects of SK&F 96365 were observed in suspensions of neutrophils and in single endothelial cells. SK&F 96365 also inhibited agonist-stimulated Mn2+ entry in platelets and neutrophils. The effects of SK&F 96365 were independent of cell type and of agonist, as would be expected for a compound that modulates post-receptor events. Voltage-gated Ca2+ entry in fura-2-loaded GH3 (pituitary) cells and rabbit ear-artery smooth-muscle cells held under voltage-clamp was also inhibited by SK&F 96365; however, the ATP-gated Ca2(+)-permeable channel of rabbit ear-artery smooth-muscle cells was unaffected by SK&F 96365. Thus SK&F 96365 (unlike the 'organic Ca2+ antagonists') shows no selectivity between voltage-gated Ca2+ entry and RMCE, although the lack of effect on ATP-gated channels indicates that it discriminates between different types of RMCE. The effects of SK&F 96365 on functional responses of cells thought to be dependent on Ca2+ entry via RMCE were also studied. Under conditions where platelet aggregation is dependent on stimulated Ca2+ entry via RMCE, the response was blocked by SK&F 96365 with an IC50 of 15.9 microM, which is similar to the IC50 of 8-12 microM observed for inhibition of RMCE. Adhesion and chemotaxis of neutrophils were also inhibited by SK&F 96365. SK&F 96365 is a useful tool to distinguish RMCE from internal Ca2+ release, and to probe the role of RMCE in mediating functional responses of cells. However, SK&F 96365 is not as potent (IC50 around 10 microM) or selective (also inhibits voltage-gated Ca2+ entry) as would be desirable, so caution must be exercised when using this compound.

Adenosine Diphosphate↗
PubMed1990

Effects of a diet rich in Q-3 fatty acids on left ventricular geometry and dynamics in spontaneously hypertensive rats.

The aim of the present study was to investigate the chronic effects of a dietetic antihypertensive treatment on blood pressure, ventricular dynamics and geometry of the pressure loaded heart. Spontaneously hypertensive rats (SRH) received a standard diet enriched with 10% mackerel oil, containing 30% polyunsaturated Q-3 fatty acids, over a period of 70 days. As described previously the diet reduced blood pressure permanently by 40-50 mm Hg. Despite this reduction, the degree of left ventricular hypertrophy was only slightly (statistically insignificantly) reduced. This was probably a result of an increase in sympathetic tone as indicated by a raised pulse rate. On the other hand, the treatment prevented the development of eccentric hypertrophy, typical to the SHR, without changing the elastic material properties of the myocardium. Since the age-matched controls did not show significant degenerative alterations, protective effects at the level of myocardial tissue could not be demonstrated. Furthermore, future investigations need to investigate why myocardial contractility of the treated animals diminishes as observed in this study.

Animals↗
PubMed1990

Left ventricular performance in rats with chronic cardiac overload due to arterio-venous shunt.

The effects of experimental arterio-venous shunt (AV shunt) on left ventricular dynamics and myocardial mechanics were investigated in female Wistar rats, weighing approx. 240 g. The main goal of the study was to characterize ventricular and myocardial working capacity and to estimate the significance of the various processes involved in cardiac adaptation to the altered loading conditions. Twelve weeks after operation, systemic blood pressure was slightly elevated in AV shunt rats as compared with age-matched controls, although total peripheral resistance (as related to a common aortic pressure) was significantly reduced. Heart rate and cardiac output were considerably increased. Despite marked left ventricular dilatation with increased end-diastolic and systolic wall stress, no signs of resting insufficiency were present. Left ventricular weight, end-diastolic volume and pressure, stroke volume, and ejection fraction were increased. The area between the curve of isovolumic maxima and the end-diastolic P-V curve (up to a defined end-diastolic pressure) and the normalized area between the isovolumic and end-diastolic stress-length curves as well as the maximum rate of stress development were augmented, even in the specimen with the highest degree of ventricular dilatation--despite a shift of the myosin isoenzyme pattern towards VM3. The study reveals that besides the change in ventricular mass and configuration, augmented preload is involved in cardiac adaptation to the altered hemodynamic state. Furthermore, there are indications of an intensified sympathetic stimulation of the heart. Transformation of the myocardium towards a slower muscle seems to be of minor functional significance under the conditions of the present experiments.

Adaptation, Physiological↗
PubMed1990

Agonist-stimulated divalent cation entry into single cultured human umbilical vein endothelial cells.

1. The free cytoplasmic Ca2+ concentration ([Ca2+]i) can be measured using Fura-2 in superfused single human umbilical vein endothelial cells. When an endothelial cell is stimulated by a maximal dose of histamine (100 microM), [Ca2+]i rises to a peak and then falls back to a maintained plateau which is due to a stimulated Ca2+ influx. 2. If extracellular Ca2+ is replaced by 50 microM-Mn2+ then 100 microM-histamine causes a rise in [Ca2+]i accompanied by a fluorescence quench that signals the stimulated entry of Mn2+ into the cytoplasm. 3. If in Ca2(+)-free solution a cell is stimulated by 100 microM-histamine for 120 s to discharge the internal Ca2+ store, and then exposed to 50 microM-Mn2+ after removal of the histamine, a similar stimulated Mn2+ entry is seen. This quench is unaffected by readdition of histamine and is not seen if the store is refilled by exposure to 1 mM-extracellular Ca2+ for 180 s before exposure to the Mn2+. 4. The refilling of the internal store by exposure to 1 mM-Ca2+ and the stimulated entry of Mn2+ are both blocked by 2 mM-Ni2+. 5. If [Ca2+]i is stimulated to produce repetitive spikes by a low dose of histamine (0.3-1 microM) in nominally Ca2(+)-free solution containing Mn2+, then the stimulated quench is uniform and is not modulated by the [Ca2+]i spiking. 6. If the internal store is discharged by exposure to histamine in Ca2(+)-free solution and then refilled for a short period then the cell is in a state where the internal store is partly full to an extent that depends on the duration of the refilling. In such an experiment, the rate of Mn2+ influx may be estimated by measuring the rate of quench during a short exposure to 50 microM-Mn2+. The rate of Mn2+ entry varies inversely with the degree of fullness of the internal Ca2+ store. 7. If a similar experiment is repeated but with the fullness of the internal store being varied by varying the period of the initial exposure to 100 microM-histamine, with no refilling, the same inverse relationship between Mn2+ influx and fullness of the internal store is obtained. 8. These experiments show that Mn2+ enters human umbilical vein endothelial cells following agonist stimulation by a pathway that is controlled by the degree of fullness of the internal store; it does not, however, enter the cytoplasm by exactly the same route as Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1990

The perioperative effects of oral premedication in children.

The pre- and postoperative effects of oral diazepam (0.5 mg/kg), trimeprazine (4 mg/kg), pentobarbitone (3 mg/kg) and a placebo were compared in a randomized double-blind clinical trial in 149 children, aged one to ten years, undergoing adenotonsillectomy. The anaesthetic was standardised and each patient received intraoperative intramuscular papaveretum (0.3 mg/kg). Preoperative sedation was assessed in the ward before transfer onto the theatre trolley, on leaving the ward, on arrival on the theatre floor, on arrival in the induction room and on induction of anaesthesia. There was no significant difference in sedation between the four drug groups except for the placebo group which had a significantly greater unsatisfactory rating at the stage of induction of anaesthesia (P = 0.001). There were no differences in waking times between the diazepam, pentobarbitone and placebo groups, but the trimeprazine group's waking times were significantly prolonged (P less than 0.001). However, the trimeprazine group exhibited significantly less distress in the recovery unit (P = 0.02) and had half the incidence of vomiting (P less than 0.001) than did the other premedication groups.

Adenoidectomy↗