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Biomedical subjects

M Block

Publications and source records attributed to M Block.

At least 127 records · Page 7Linked to original sources

Ultrastructural abnormalities of mitochondria and deficiency of myocardial cytochrome c oxidase in a patient with ventricular tachycardia.

A 30-year-old woman presented with life-threatening ventricular tachycardia without overt heart disease. Ultrastructural investigation of endomyocardial biopsy disclosed abnormally structured and often enlarged mitochondria. Morphometry revealed the ratio of volume density of mitochondria to myofibrils to be markedly increased to 0.667 as compared with five controls (mean: 0.46; range: 0.445-0.479). Investigation of mitochondrial respiratory chain enzymes revealed a 90% reduction in activity of cytochrome c oxidase. Our data suggest that mitochondrial cardiomyopathy may induce malignant ventricular arrhythmias.

Adult↗

Decreased norepinephrine and epinephrine contents in chromaffin tissue of rainbow trout (Oncorhynchus mykiss) exposed to diethyldithiocarbamate and amylxanthate.

1. Rainbow trout (Oncorhynchus mykiss) were exposed to 0.5 or 5.0 microM of diethyldithiocarbamate (DDC) or amylxanthate (AX) for 24 hr. 2. Both DDC (0.5-5.0 microM) and AX (5.0 microM) significantly decreased norepinephrine and epinephrine levels in the head kidney as well as the quotients epinephrine/dopamine and/or norepinephrine/dopamine. 3. The results probably reflect an inhibition of dopamine-beta-hydroxylase, the enzyme responsible for the synthesis of norepinephrine and epinephrine from dopamine. 4. It is concluded that an exposure of fish to these complexing agents could disturb physiological processes controlled by catecholamines. 5. Diethyldithiocarbamate may prove to be a valuable pharmacological tool for the study of catecholamine function in fish.

Animals↗

Implantable cardioverter/defibrillators (ICD): a new lead-system using transvenous-subcutaneous approach in patients with prior cardiac surgery.

The current approach in cardioverter-defibrillator implantation requires placement of epicardial leads which may lead to pericardial and/or pleural effusion and pneumonia during the perioperative period. Although ICD implantation is less invasive than other surgical techniques for the treatment of rhythm disturbances, the perioperative mortality must be considered. Minimizing the operative procedure could lead to a reduction in perioperative mortality. Therefore, we investigated an approach without the need for thoracotomy using a transvenous/subcutaneous lead system. In nine patients with prior cardiac surgery, defibrillator implantation was performed by a transvenous/subcutaneous approach. There was no perioperative mortality. In all patients, a sufficient defibrillation threshold was achieved. The defibrillation pulses were delivered as two sequential pulses between a right ventricular electrode (cathode) and a coronary sinus or superior caval vein electrode (anode 1) and a subcutaneous patch electrode (anode 2). Intubation of the coronary sinus was necessary in 4 patients in order to obtain satisfactory defibrillation thresholds. These data demonstrate that a transvenous/subcutaneous approach is feasible in patients with prior cardiac surgery obviating the need for thoracotomy. Sensing function of the RV-electrode, intubation of the coronary sinus and the intraoperative use of an epicutaneous patch electrode are current problems of this new technique.

Adult↗

Smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy.

Effects of smoking-cessation treatment combining transdermal nicotine substitution with behavioral therapy were investigated in two studies. A total of 403 smokers underwent nine weeks of behavioral self-control treatment. For seven weeks, groups with transdermal nicotine substitution were also provided with nicotine patches that continuously release nicotine through the skin into the circulatory system. The effects of treatment were measured by total abstinence. The results showed that the nicotine concentration in the patch, special relapse prevention methods, and the type of dosage (individual versus fixed dose) had no influence on therapeutic success. Nicotine concentration played a decisive role in the compatibility of the patch. Combining transdermal nicotine substitution with behavioral therapy produced 12-month success rates (total abstinence) of about 35%.

Administration, Cutaneous↗

Cardiopulmonary effects of internal cardioverter/defibrillator implantation.

Cardiopulmonary effects of electrophysiological testing of internal cardioverter/defibrillator (ICD) devices were studied in ten patients undergoing general anaesthesia. In the control-phase, haemodynamic performance and oxygenation were slightly impaired. After completion of the electrophysiological procedures (ICD-phase), cardiopulmonary function had deteriorated significantly. Cardiac index declined by 16%, whereas left ventricular filling pressure and pulmonary vascular resistance increased (P less than or equal to 0.01). Oxygenation, but not CO2-elimination deteriorated (P less than or equal to 0.01) and venous admixture increased by 72% (P less than or equal to 0.01). Alveolo-arterial PO2-difference (PA-aO2) increased by 43% (P less than or equal to 0.01), indicating ventilation-perfusion (VA/Q) mismatching. Repeated inductions of ventricular tachycardia and/or fibrillation subject the myocardium to transient global ischaemia, leading to acute congestive heart failure, and positive inotropic intervention was necessary in 40% of the patients. Partial pulmonary insufficiency resulted possibly from interstitial oedema and VA/Q-inhomogeneities. ICD implantation has detrimental effects on haemodynamics and gas exchange in patients with impaired left ventricular function.

Aged↗

[Initial clinical experiences with a transvenous-subcutaneous defibrillation system].

In 19 patients with an indication for an implantable defibrillator, it was tried to avoid thoracotomy by using two electrodes positioned via the subclavian vein in the right ventricle (for pacing, sensing, and defibrillation) and the superior vena cava or coronary sinus (for defibrillation), and one electrode positioned subcutaneously near the ventricular apex (for defibrillation). In 17 patients (89%) the transvenous-subcutaneous leads were implanted, whereas in the remaining two patients an epi-/pericardial lead system was subsequently used due to an insufficient defibrillation threshold. Perioperatively, no major complications were observed and patients were rapidly mobilized. Within a follow-up period of 7 +/- 4 months, no malfunction of the lead system became evident. Sixty-eight episodes of spontaneous ventricular tachyarrhythmias occurred, all of which were successfully terminated. In one patient an infection of the lead system developed after 2 months that proved refractory to antibiotics and required surgical removal. Thus, transvenous-subcutaneous placement of leads for implantable defibrillators yielded a sufficient defibrillation threshold in the majority of patients. Long-term efficacy was excellent and no malfunctions were observed. This approach seems to be feasible and advisable in patients with an increased risk for thoracotomy.

Adolescent↗

Envelope membranes from mature spinach chloroplasts contain a NADPH:protochlorophyllide reductase on the cytosolic side of the outer membrane.

Using fluorescence spectroscopy, we have demonstrated that isolated envelope membranes from mature spinach chloroplasts catalyze the phototransformation of endogenous protochlorophyllide into chlorophyllide in presence of NADPH, but not in presence of NADH. Protochlorophyllide reductase was characterized further using monospecific antibodies (anti-protochlorophyllide reductase) raised against the purified enzyme from oat. In mature spinach chloroplasts, protochlorophyllide reductase is present only in envelope membranes. We have demonstrated that the envelope protochlorophyllide reductase, a 37,000-dalton polypeptide, is only a minor envelope component and is present on the outer surface of the outer envelope membrane. This conclusion is supported by several lines of evidence: (a) the envelope polypeptide that was immunodecorated with anti-protochlorophyllide reductase can be distinguished from the major 37,000-dalton envelope polypeptide E37 (which was identified by monospecific antibodies) only after two-dimensional polyacrylamide gel electrophoresis; (b) the envelope protochlorophyllide reductase was hydrolyzed when isolated intact chloroplasts were incubated in presence of thermolysin; and (c) isolated intact chloroplasts strongly agglutinate when incubated in presence of antibodies raised against protochlorophyllide reductase. These results demonstrate that major differences exist between chloroplasts and etioplasts with respect to protochlorophyllide reductase levels and localization. The presence on the chloroplast envelope membrane of both the substrate (protochlorophyllide) and the enzyme (protochlorophyllide reductase) necessary for chlorophyllide synthesis could have major implications for the understanding of chlorophyll biosynthesis in mature chloroplasts.

Chloroplasts↗

Pulmonary fibrosis associated with low-dose adjuvant methyl-CCNU.

Pulmonary fibrosis is a serious side effect of nitrosourea therapy, occurring most frequently in patients treated with BCNU. Pulmonary fibrosis developed in a 63 year-old male patient while being treated with adjuvant methyl-CCNU for rectal carcinoma. This toxicity is rare with methyl-CCNU, having only been reported once previously. The case of methyl-CCNU-induced pulmonary fibrosis reported here occurred at a much lower total dose than the first reported case (604 mg/m2 vs. 2,733 mg/m2). Details of the case history, including radiographic and pathologic findings, are presented.

Antineoplastic Combined Chemotherapy Protocols↗

Primary lymphoma of bone.

Primary lymphoma of bone is a rare clinical entity that accounts for less than one per cent of all non-Hodgkin's lymphomas. Although they occasionally present as a solitary lesion in bone, lymphoma involving bone is a manifestation of disseminated disease in many instances. All patients initially found to have a solitary lymphoma of bone need to be thoroughly investigated for systemic disease because more than half of the patients presenting with initially solitary bone lesions are found to have systemic disease involving lymph nodes and/or other organs. Choice of therapeutic management is based on the stage of disease. Stage I-E primary lymphoma of bone can be controlled in 70-90% of cases using local radiation therapy alone if adequate radiation doses are used. Patients with advanced disease should be treated with combination chemotherapy in addition to local radiotherapy. Loeffler et al reported long-term survival results of 90% 8-year actuarial overall survival rate for children with primary lymphoma of bone who received combined therapy with radiation and chemotherapy (adriamycin, prednisone and oncovin). The actuarial lymphoma-free survival rate was 100% at eight years. Regardless of stage of the disease, radiation treatment to the primary tumor appears to be critical for adequate local control of disease as well as rapid symptomatic relief.

Adult↗

Falling among the sensorially impaired elderly.

Recent studies of the healthy elderly indicate that accidental falls account for many lengthy hospital stays and permanent disabilities. An ongoing investigation by our group is examining the contribution of neuromuscular feedback and the possible substitution of visual-perceptual feedback as a major contributor to falling in this population. This combination of decreased weighting of neuromuscular factors and increased weighting of the visual-perceptual factors led to the following hypothesis: Those persons who cannot see should show less change in frequency of falling as they age than sighted cohorts. The deaf, who rely more than others on visual perceptual stimuli, are less likely to fall as they age than the general elderly population, who first begin to rely more heavily on visual stimuli when they age. Thus, the deaf and blind constitute a population whose change in frequency of falls with increased age should differ markedly from change in the frequency of falls among the nonblind and nondeaf segments of the population. Our results support the hypothesis. The blind demonstrated a higher rate of falls than the deaf or nonimpaired population. However, the more elderly blind failed to show the increase in falling demonstrated by the deaf and nonimpaired. If these findings are confirmed in subsequent studies, the nonimpaired and deaf elderly could be trained to focus on visual feedback. The blind may be able to reduce the frequency of falls by enhancing musculoskeletal feedback and strength via exercise.

Accidental Falls↗

[The reliability of angiographic volume determination of the left ventricle using digital image subtraction--significance in stress tests].

Using the technique of digital subtraction angiography (DSA), left ventricular volumes can be determined after intravenous injection of contrast medium at rest and during exercise. The significance of the well known errors of angiographic determination of left ventricular volumes was investigated in 22 patients before and during a bicycle exercise test. Before and after exercise 40 ml of contrast medium were injected (18 ml/s) intravenously to calculate left ventricular volumes. Enddiastolic and endsystolic contours of the left ventricle were traced by two investigators (A and B) on five different days. Using these contours, volumes were calculated by a computer system. The first calculation of both investigators (single measurement) and the mean value of all five calculations (repetitive measurements) were compared. In the same procedure left ventricular contours of six patients were calculated after conventional contrast ventriculography (40 ml of contrast medium). No systematic deviations were found in comparing the results of both investigators using the single or repetitive method by means of DSA: (VolB = 0.86 VolA + 12.2, r = 0.97 versus VolB = 0.96 VolA + 9.1, r = 0.99). Compared to single method the residuals (Syx) of the repetitive method were significantly smaller: Syx = +/- 16.3 ml vs +/- 8.9 ml (p less than 0.01). Similar results were found in conventional ventriculography: single method Syx = +/- 18.7 ml and repetitive method Syx = +/- 8.8 ml (p less than 0.01). Comparing the volumes determined by DSA and by conventional ventriculography, respectively, no significant differences were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

The effect of different dosages of a transdermal nicotine substitution system on the success rate of smoking cessation therapy.

The effectiveness of different nicotine dosages on abstinence rates was investigated in a smoking cessation study. One hundred smokers underwent nine weeks of self-controlled treatment based on behavioral principles. The overall group was divided into two subgroups randomized according to sex, cigarette consumption and age. The first group (n = 51) was given a nicotine dose adapted to daily cigarette consumption. The second group (n = 49) was given a standardized dose. There was, unexpectedly, no difference between the two groups in respect to short-term abstinence rates. These results suggest that standardized dosage is preferred to individually adapted dosage.

Administration, Cutaneous↗

Contact allergies induced by TTS-treatment.

The efficiency of a nicotine-containing transdermal therapeutic system (TTS) was investigated in a clinical study, the purpose of which was to help 183 heavy smokers give up their addiction by systematic and continuous nicotine application and simultaneous behavioral therapy. During the treatment period, 53% of the patients complained of pruritus and 39% developed erythemas that were almost exclusively confined to those areas where the patches had been applied. However, most symptoms appeared only in slight or moderate forms. In contrast to irritative cutireactions, 6 patients developed a genuine contact allergy (type IV, delayed type reaction) which proved in 5 cases to be induced by the nicotine contained in the patches. Presumably TTS-treatment may induce contact allergies to pharmaceutic agents, as has already been described in other observations on allergies to haptens.

Administration, Cutaneous↗

Ascorbate antagonizes the behavioral effects of amphetamine by a central mechanism.

The behavioral response to amphetamine was monitored in rats that received simultaneous intraventricular infusions of saline or ascorbate. Both groups of animals displayed comparable responses, although ascorbate significantly delayed the onset of amphetamine-induced locomotion and rearing. In rats pretreated with a threshold dose of haloperidol (0.025 mg/kg), virtually all aspects of the amphetamine response were attenuated, and this effect was enhanced by ascorbate. In haloperidol-pretreated rats, ascorbate significantly lowered sniffing and forepaw shuffling throughout the amphetamine response. These results suggest that ascorbate antagonizes dopaminergic transmission by a central mechanism.

Amphetamine↗

Metabolic and ultrastructural abnormalities during ischemia in canine myocardium: noninvasive assessment by positron emission tomography.

Positron emission tomography allows the noninvasive assessment of regional myocardial blood flow and metabolism. The purpose of this study was to correlate N-13 ammonia uptake as a measure of regional blood flow and C-11 palmitate kinetics as a marker for fatty acid metabolism in ischemic canine myocardium using positron emission tomography. Furthermore, the metabolic results were compared with ultrastructural findings obtained in the same animal model. Regional ischemia was induced by balloon occlusion of the left anterior descending artery in a closed chest dog model. The three myocardial sites studied were the center and "border" of the ischemic segment as well as the control myocardium. C-11 palmitate uptake closely correlated with blood flow (r = 0.88). In the center of ischemia uptake of C-11 palmitate was decreased and clearance of C-11 activity significantly prolonged. In the "border" of the ischemic segment with only mild reduction of flow and C-11 palmitate uptake (approximately 20%) clearance halftime and residual activity were significantly different from control. The residual activity normalized for initial uptake of C-11 palmitate was highest in the "border" regions consistent with increased deposition of C-11 palmitate in lipid pools. The electron microscopic studies showed in 8 of 11 dogs lipid droplets as the only abnormality in corresponding segments with only mild reduction in microsphere blood flow. Thus, these data indicate the potential of metabolic imaging to characterize ischemia on a cellular level. Positron emission tomography provides a sensitive means to detect mild ischemia and to define extent and severity. Metabolic imaging may prove clinically useful to identify not only necrosis, but also myocardium at risk.

Ammonia↗