Showing papers by "Mayo Clinic published in 1977"
TL;DR: A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described, based as closely as possible on ionic currents which have been measured by the voltage‐clamp method.
Abstract: 1. A mathematical model of membrane action potentials of mammalian ventricular myocardial fibres is described. The reconstruction model is based as closely as possible on ionic currents which have been measured by the voltage-clamp method.2. Four individual components of ionic current were formulated mathematically in terms of Hodgkin-Huxley type equations. The model incorporates two voltage- and time-dependent inward currents, the excitatory inward sodium current, i(Na), and a secondary or slow inward current, i(s), primarily carried by calcium ions. A time-independent outward potassium current, i(K1), exhibiting inward-going rectification, and a voltage- and time-dependent outward current, i(x1), primarily carried by potassium ions, are further elements of the model.3. The i(Na) is primarily responsible for the rapid upstroke of the action potential, while the other current components determine the configuration of the plateau of the action potential and the re-polarization phase. The relative importance of inactivation of i(s) and of activation of i(x1) for termination of the plateau is evaluated by the model.4. Experimental phenomena like slow recovery of the sodium system from inactivation, frequency dependence of the action potential duration, all-or-nothing re-polarization, membrane oscillations are adequately described by the model.5. Possible inadequacies and shortcomings of the model are discussed.
1,414 citations
01 May 1977
TL;DR: Findings provide unambiguous evidence for a destructive auto-immune reaction involving the postsynaptic membrance in MG and suggest that immunopharmacologic blockade of AChR and IgG-induced modulation of A ChR may also contribute to the A chR deficiency at the MG end-plates.
Abstract: Although there is strong evidence that myasthenia gravis (MG) is caused by an autoimmune reaction to the nicotinic postsynaptic acetylcholine receptor (AChR) protein, immune complexes have never been directly demonstrated at the end-plate by immunocyto-chemistry or immunoelectron microscopy. Staphylococcal protein A (which binds to the Fc region of human IgG subclasses 1, 2, and 4) and rabbit anti-human C3 conjugated with peroxidase were used for the ultrastructural (5 patients) and light microscopic (12 patients) localization of IgG and C3, respectively, at MG end-plates. Both IgG and C3 were localized on segments of the postsynaptic membrance and fragments of degenerating junctional folds in the synaptic space. In nonmyasthenic control patients no immune complexes were evident at the end-plate. As judged by morphometric analysis of electron micrographs, the immune complexes were more abundant in the less severely affected MG patients than in the more severely affected ones. A linear correlation was demonstrated between the length of the postsynaptic membrance binding immune complexes and the amplitude of the miniature end-plate potential. The less intense reaction for immune complexes in the more severely affected MG patients can be attributed to the smaller quantity of AChR remaining at their end-plates. The findings provide unambiguous evidence for a destructive auto-immune reaction involving the postsynaptic membrance in MG. Immunopharmacologic blockade of AChR and IgG-induced modulation of AChR may also contribute to the AChR deficiency at the MG end-plates.
410 citations
TL;DR: Results suggest that the ATPase activator is closely related to Ca 2+ binding proteins from a number of sources, and to skeletal muscle troponin-C as well.
374 citations
TL;DR: The association of three uncommon neoplasms — gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma — in two patients and the occurrence of two of these tumors in ...
Abstract: The association of three uncommon neoplasms — gastric leiomyosarcoma, functioning extra-adrenal paraganglioma and pulmonary chondroma — in two patients and the occurrence of two of these tumors in ...
364 citations
TL;DR: Light emission from the calcium-sensitive bioluminescent protein aequorin was measured at calcium ion concentrations of 10(-9) to 10(-2) molar and the complete relation is well described by a two-state model involving three calcium-binding sites.
Abstract: Light emission from the calcium-sensitive bioluminescent protein aequorin was measured at calcium ion concentrations of 10(-9) to 10(-2) molar. At very low Ca2+ concentations, light emission is independent of calcium ion concentration. The maximum slope of the log-log plot of light as a function of calcium ion concentration is about 2.5. The complete relation is well described by a two-state model involving three calcium-binding sites.
353 citations
TL;DR: It is suggested that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of Corticosteroids on depressing transmucosal intestinal absorption of calcium.
Abstract: Pharmacologic doses of corticosteroids impair intestinal calcium absorption and contribute to negative calcium balance. However, the relationship between the impaired calcium absorption and a possible defect in the conversion of vitamin D to its physiologically active form, 1,25-dihydroxyvitamin D, is unknown. We compared fractional calcium absorption (double-isotope method, 100-mg carrier) and serum 25-hydroxyvitamin D (25-OH-D) (Haddad method) in 27 patients receiving pharmacologic doses of prednisone with 27 age-, sex-, and season-matched normal subjects. In patients receiving high daily doses of prednisone (15-100 mg/day), calcium absorption (P < 0.02) and serum 25-OH-D (P < 0.001) were decreased. However, in patients receiving low doses (8-10 mg/day) or high doses (30-100 mg) of prednisone on an alternate-day schedule, both of these parameters were normal. Calcium absorption in the patients treated with daily prednisone correlated inversely with the dose of corticosteroids (r = −0.52, P < 0.025) and, in all steroid-treated patients, correlated directly with serum 25-OH-D (r = 0.58, P < 0.01). In four patients who received high-dose corticosteroid therapy for an average of 4 wk, serum 25-OH-D decreased by 35.5% from pretreatment values. Administration of a physiologic or near-physiologic dose of synthetic 1,25-dihydroxyvitamin D3 (0.4 μg daily for 7 days) to patients receiving high-dose corticosteroids led to an increase in calcium absorption in all patients. These results suggest that calcium malabsorption in the corticosteroid-treated patients is due to a dose-related abnormality of vitamin D metabolism and not to a direct effect of corticosteroids on depressing transmucosal intestinal absorption of calcium.
329 citations
TL;DR: Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, it is recommend it.
Abstract: To assess the fate and efficacy of orally ingested enzymes in pancreatic insufficiency, we administered pancreatin to six patients by two schedules--eight tablets with a standard meal or two tablets hourly--and in six normal controls, quantified duodenal enzyme activity and related inactiviation of ingested enzymes to gastric and duodenal pH; in the six patients we measured malabsorption by fecal balance studies. Postprandially, gastric pH was similar in health and pancreatic insufficiency, and below 4 after 40 minutes. Duodenal pH in pancreatic insufficiency declined to approximately 4 beyond 100 minutes--lower than in health (P less than 0.05). Approximately 22 per cent and 8 per cent of trypsin and lipase activity ingested with either schedule was delivered to the ligament of Treitz. Prandial was as effective as hourly administration in decreasing steatorrhea and perhaps more effective in abolishing azotorrhea, and since it is also more convenient, we recommend it.
268 citations
Journal Article•
TL;DR: Catechol-O-methyltransferase activity was measured in blood obtained from 373 randomly selected subjects aged 16-18, 262 consecutive adult blood donors, and 201 first-degree relatives of subjects with RBC COMT activity of less than 8 U and the results of segregation analyses of the data were compatible with autosomal recessive inheritence of an allele for low RBCCOMT activity.
Abstract: Catechol-O-methyltransferase activity was measured in blood obtained from 373 randomly selected subjects aged 16-18, 262 consecutive adult blood donors, and 201 first-degree relatives of subjects with RBC COMT activity of less than 8 U. The distribution of RBC COMT activity in a randoly selected populations was apparently bimodal with a nadir at approximately 8 U. Of a randomly selected population, 23% had low RBC COMT activity (less than 8 U), Because of previous reports of a significant sibling-sibling correlation of RBC COMT activity and because of the presence of a subgroup of subjects with low enzyme activity, RBC COMT activity was measured in blood from first-degree relatives of probands with low erythrocyte enzyme activity in 48 families. The results of segregation analyses of the data were compatible with autosomal recessive inheritence of an allele for low RBC COMT activity. RBC COMT in blood samples from siblings of probands inthese families also showed an apparent biomodal distribution.
249 citations
246 citations
TL;DR: The tracheal cartilages receive nourishment from the capillary bed applied to their internal surface from the inferior thyroid, subclavian, supreme intercostal, internal thoracic, innominate, and superior and middle bronchial arteries.
245 citations
TL;DR: In this paper, what do consumers do with products once they have outlived their usefulness, and how does this relate to the purchase of replacement products? And how do consumers buy replacement products when they outlive their usefulness?
Abstract: What do consumers do with products once they have outlived their usefulness, and how does this relate to the purchase of replacement products?
TL;DR: The low rate of use of conjugated estrogens in Olmsted County, Minnesota over the past 30 years apparently has not had an appreciable impact on the incidence of endometrial cancer.
TL;DR: Peroxidase-conjugated α-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in end-plates in external intercostal muscles of four patients with myasthenia gravis, in forelimb digit extensor muscles of rats with advanced chronic experimental autoimmune myasthensia Gravis, and in suitable human and rat controls.
Abstract: Peroxidase-conjugated alpha-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in end-plates in external intercostal muscles of four patients with myasthenia gravis, in forelimb digit extensor muscles of rats with advanced chronic experimental autoimmune myasthenia gravis, and in suitable human and rat controls. In control end-plates, the previously reported localization of acetylcholine receptor on the terminal expansions of the postsynaptic folds and, in traces, on the presynaptic membrane was confirmed. By contrast, in myasthenia gravis some postsynaptic regions bound no P-BGT; in other regions, the folds displayed only faint traces of the reaction product, or only some segments of the postsynaptic membrane showed the reaction product; finally, in some regions there was no apparent decrease in reaction product. In general, those postsynaptic regions showing the greatest decrease in P-BGT binding were also the simplest or showed the most degenerative changes, and the presynaptic staining was decreased in proportion to the decrease in the adjacent postsynaptic P-BGT binding. In the experimental animals, the abnormalities in the amount and distribution of the acetylcholine receptor were essentially like those in the more severely affected patients. Morphometric estimates of the postsynaptic acetylcholine receptor surface correlated well with the patients' clinical status and linearly with the miniature end-plate potential amplitude.
TL;DR: Steady-state and dynamic descriptions of the enterohepatic circulation of bile acids in healthy men are given in this article, where a method for characterizing the bile acid circulation in health and disease is presented.
Abstract: Steady-state and dynamic descriptions of the enterohepatic circulation of bile acids in healthy man are given Methods for characterizing the enterohepatic circulation of bile acids in health and disease are summarized
TL;DR: Successful assessments of gastric, jejunal, ileal, and colonic permeability suggest that the PEG 400 technique has application to any area of the gastrointestinal tract.
TL;DR: This retrospective study summarizes the clinicopathologic findings in 110 children with fibrosarcoma and believes that infants and children less than 5 years old may be treated initially by local excision of the lesion, without sacrificing significant function of the part.
Abstract: This retrospective study summarizes the clinicopathologic findings in 110 children with fibrosarcoma. Seventy cases were selected from previous reports and 40 were from our files. The histologic criteria used for diagnosis are the same as those used for adults. Sixty-eight patients were in the first quinquennium of life, 13 in the second, and 29 in the third. Eleven patients died of their tumor, three in the first quinquennium and eight in ght third. Our findings indicate that children who are less than 5 years old have a 7.3% chance of developing metastatic spread even though the local recurrence rate is 43%. Children who are 10 years old or older had a metastatic rate of 50% at 5-year follow-up, a figure closely approximating that for adults. We believe that infants and children less than 5 years old may be treated initially by local excision of the lesion, without sacrificing significant function of the part. Recurrent tumor does not seem to predispose to metastatic disease.
TL;DR: A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs.
Abstract: A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.
TL;DR: It appears that prothrombin fragment 1 has two classes of metal ion binding sites, probably comprising two of six sites, which are apparently fairly nonselective with respect to which metal ion is bound; binding of metal ions to these sites is responsible for the fluorescence change and apparently triggers a conformational transition.
TL;DR: In this paper, a new approach to the measurement of intestinal permeability in man has been developed, using low molecular weight polyethylene glycol (PEG 400) as probe molecules.
TL;DR: The correct designation for these tumors in the light of current knowledge is malignant tumor, consistent with malignant (fibrous) histiocytoma.
Abstract: Malignant (fibrous) histiocytoma is currently defined as a malignant primary bone tumor that contains a mixture of fibrogenic cells and cells that are histologically similar but which appear to be histiocytic. In this type of histiocytoma the nuclei are often indented; cytoplasm is usually abundant and may be slightly foamy; nucleoli are often large; and multinucleated malignant cells are usually a prominent feature. Many dedifferentiated chondrosarcomas, osteosarcomas, and fibrosarcomas of bone contain areas that resemble what we regard as malignant (fibrous) histiocytoma. When the entirety of a malignant tumor of bone fits the outlined histologic pattern, the designation of malignant (fibrous) histiocytoma seems appropriate. From 158 fibrosarcomas of bone and 962 osteosarcomas of bone in our files, 35 tumors were segregated because they appeared to be properly designated as malignant (fibrous) histiocytoma. A wide age range was represented by affected patients, and a large variety of bones harbored these tumors. Approximately one-third of patients eligible for 5-year follow-up were long-term, symptom-free survivors. Four deaths occurred from the tumor after more than 5 years, and one patient had radiographic evidence of pulmonary metastasis 7 years after amputation. Radiation therapy has been curative in at least two cases. The correct designation for these tumors in the light of current knowledge is malignant tumor, consistent with malignant (fibrous) histiocytoma.
TL;DR: A prospective study of the incidence of endometriosis encountered in consecutive pelvic explorations was carried out, and conclusions were drawn as to risks and benefits referable to the type of operation performed.
TL;DR: In eight dogs, cellotomy, rubbing the small bowel, and exposing it to air suppressed the migrating bursts of action potentials and contractions that occur in the gastrointestinal tract during fasting and greatly slowed the gastrointestinal transit of 7-mm plastic spheres.
Abstract: • In eight dogs, celiotomy, rubbing the small bowel, and exposing it to air suppressed the migrating bursts of action potentials and contractions that occur in the gastrointestinal tract during fasting and greatly slowed (one to three days) the gastrointestinal transit of 7-mm plastic spheres. The operation also caused a transient one-day increase in the concentration of epinephrine and a more prolonged five-day increase in the concentration and norepinephrine in arterial and venous plasma. Phentolamine mesylate and propranolol hydrochloride prevented the inhibition of the bursts of gastric action potentials brought about by operation, but these drugs did not alter the inhibition of the small intestinal action potentials or the speed of gastrointestinal transit of spheres. ( Arch Surg 112:203-209, 1977)
TL;DR: In selected patients after cardiac surgery, temporary A-V sequential pacing is a workable and valuable adjunctive form of hemodynamic support and is preferable to ventricular or atrial pacing.
Abstract: The hemodynamic effects of atrioventricular (A-V) sequential pacing were assessed and compared with those of ventricular and of atrial pacing in 10 patients with and without heart block after cardiac surgery. Ventricular pacing alone was either hemodynamically detrimental or of no benefit in six of the eight patients who initially had sinus or accelerated junctional rhythms. Atrial pacing alone produced significant improvement in cardiac output in all patients who were not pacemaker-dependent. However, five of the eight patients with intact A-V conduction had further increases in cardiac output through A-V sequential pacing at shorter than intrinsic A-V intervals. Optimal A-V intervals for maximal cardiac output could be identified in all patients and varied widely. Significant changes in cardiac output occurred with relatively small deviations in the A-V interval. In selected patients after cardiac surgery, temporary A-V sequential pacing is a workable and valuable adjunctive form of hemodynamic support and is preferable to ventricular or atrial pacing.
TL;DR: Inverting papilloma of the nose and paranasal sinuses has been classified as a true neoplasm by most authors.
Abstract: A series of 30 patients with inverted papillomas of the nose and/or the paranasal sinuses is presented. The inverted papilloma is a rare tumor with an overall incidence varying from 0.5% to 4% of all primary nasal tumors. The incidence of inverted papilloma is much more common in the fifth to seventh decades. An association between inverted papilloma and carcinoma is well established. In the large series of patients, the incidence of malignancy associated with inverted papilloma ranges from 1% to 13%, and in our series 10%. Treatment of inverted papilloma is always surgical. The incidence of recurrence is directly related to the method of surgical treatment. Among our 20 patients who were treated by limited surgery, there was recurrence in 14 cases (70%). By contrast, medial maxillectomy and ethmoidectomy via lateral rhinotomy reduced the recurrence rate dramatically. In our opinion this approach is the surgery of choice in the treatment of inverted papilloma.
TL;DR: The results indicate an inappropriately prolonged gastric secretory response to meals in duodenal ulcer disease, without a concomitant increase in peak postprandial secretory rates or an increase in serum immunoreactive gastrin levels.
TL;DR: Central low‐grade osteosarcomas have been misdiagnosed frequently and hence treated inadequately and careful roentgenographic and histo‐logic correlation is required to make the diagnosis.
Abstract: A series of 27 patients with intramedullary osteogenic sarcomas that were so well-differentiated histologically as to be confused with benign lesions was studied. Of the 27 patients, 14 were females and 13 were males, and most were adults. The tibia and femur were involved commonly. Roentgenographically, the tumors showed a mixture of sclerosis and lysis with poor margination. However, they lacked the highly destructive appearance of high-grade osteosarcomas. Histologically, spindle cells with minimal cytologic atypia were arranged in interlacing bundles. Mitotic figures were scarce. The amount of osteoid was variable, commonly being abundant. With recurrence, three tumors became highly anaplastic. Excision of tumor almost invariably led to recurrences. Resection or amputation has led to good results in seven patients. Only three of the 27 patients died with metastatic tumor; one patient is alive with metastasis. Central low-grade osteosarcomas have been misdiagnosed frequently and hence treated inadequately. Careful roentgenographic and histologic correlation is required to make the diagnosis.
TL;DR: The Merkel cell, a neural crest migrant to the skin, possesses a characteristic intranuclear rodlet, cytoplasmic membrane-bound granules, and horn projections and is usually associated with nerve terminations.
TL;DR: Although the malignant giant cell tumor of the pancreas might have a better prognosis, the prognosis in the other three types does not differ significantly from that of the ordinary type of pancreatic carcinoma.
Abstract: A series of 12 cases of pancreatic carcinoma with sarcoma-like transformation were studied. Four distinctive histologic types were identified: spindle cell carcinoma, malignant giant cell tumor, pleomorphic giant cell carcinoma, and round cell anaplastic carcinoma. The spindle cell carcinoma had a predominance of malignant spindle and undifferentiated cells. Hemorrhage and sarcomatoid stroma with abundant osteoclast-like giant cells were the features in the malignant giant cell tumor. The pleomorphic giant cell carcinoma was characterized by abundant malignant giant cells. The round cell anaplastic type was formed by monotonous sheaths of small, round, and plump cells with rare giant cells. The first three types are considered to be ductal in origin, whereas the fourth type is believed to arise from acinar or possibly insular tissue. The differential diagnosis includes various types of true sarcoma. Although the malignant giant cell tumor of the pancreas might have a better prognosis, the prognosis in the other three types does not differ significantly from that of the ordinary type of pancreatic carcinoma.
TL;DR: Electrical recordings were made intermittently from the fasted, conscious dogs with no pacing and during pacing of the PP in the proximal and in the distal duodenum, which caused duodenal-gastric reflux of BaSO4 in every dog and forced about 30% of the duodanal infusate into the stomach during fasting and during gastric emptying.
TL;DR: In 60 patients with a spectrum of cardiac defects and a wide range in age of presentation, studies were made of the feasibility of performing contrast echocardiography with superficial peripheral venous injections, and the clinical usefulness of this relatively noninvasive technique in detecting and localizing intracardiac right ot left shunting.
Abstract: Contrast echocardiography is the technique of injecting various echoproducing agents into the bloodstream and, with standard echocardiographic techniques, observing the blood flow patterns as revealed by the resulting cloud of echoes. These techniques have only recently been utilized to evaluate various cardiac defects. Two physical properties of these agents characterize their usefulness: (1) clouds of echoes can be observed downstream as well as at the injection site, and (2) the echoproducing quality of these agents is completely lost with a single transit through either the pulmonary or the systemic capillary bed. Thus, detection of resultant echoes in both the venous and the arterial blood pool is indicative of abnormal shunting. In 60 patients with a spectrum of cardiac defects and a wide range in age of presentation, studies were made of (1) the feasibility of performing contrast echocardiography with superficial peripheral venous injections, and (2) the clinical usefulness of this relatively noninvasive technique in detecting and localizing intracardiac right to left shunting. Most superficial peripheral veins could be utilized, and the resultant contrast echograms were reproducible and similar in quality to those obtained with more central (caval) injections. Right to left shunts could be localized to the atrial, ventricular or intrapulmonary level. Characteristic flow patterns were also recognized for tricuspid atresia and common ventricle.